METHODS OF ACQUIRING KNOWLEDGE IN NURSING.pptx by navdeep kaur
ZMPCZM016000.11.08
1. Applications of Transcutaneous Electrical Nerve
Stimulation in the Management of Patients with Pain
State-of-the-Art Update
MERYL ROTH GERSH and STEVEN L. WOLF
Numerous publications devoted to the topic of transcutaneous electrical nerve
stimulation (TENS) have appeared since the presentation of a special issue of
PHYSICAL THERAPY (December, 1978). This update article addresses contemporary
information on efficacy, mode of application, treatment outcomes, and neurophysiological mechanisms relevant to this modality. Investigators have become
far more specific when presenting this information in the current literature on
treating acute pain conditions with TENS than they were in the literature for the
1978 special issue. Improvement has been made in providing specific details to
enable replication of TENS stimulating characteristics among patients with
chronic pain; yet several clinical researchers still fail to evaluate treatment
outcomes adequately. Perhaps the greatest advances in our understanding of
TENS involve the recent development of mechanisms that might account for how
different types of TENS work. Suggestions for predicting patient responses to
TENS and for avenues of future inquiry are offered.
Key Words: Electric stimulation, Pain, Physical therapy.
A wealth of information is available
on the clinical application of transcutaneous electrical nerve stimulation
(TENS) for pain management. In recent
years, clinicians have studied the effect
of TENS on pain associated with specific pathological conditions and have
sought a relationship between specific
treatment protocols and outcomes. Authors have more closely attended to the
importance of specific electrode placements and stimulation characteristics,
so that studies on particular diagnostic
groups of patients could be compared
and replicated. More sophisticated pain
evaluation tools have been used to assess
a patient's response to TENS therapy.
The purpose of this article is to review
critically literature about TENS, which
has been generated after the publication
of a special issue on TENS in PHYSICAL
THERAPY in 1978, to determine if more
definitive information is available regarding 1) the efficacy of treatment for
specific diagnostic categories, 2) current
methods of application (specific elec-
Mrs. Gersh is a physical therapist at St. Luke's
Memorial Hospital, S 711 Cowley St, Box 288,
Spokane, WA 99210.
Dr. Wolf is Associate Professor, Department of
Rehabilitation Medicine, Emory University School
of Medicine, 1441 Clifton Rd, NE, Atlanta, GA
30322 (USA) and a senior investigator, Emory University Rehabilitation Research and Training Center, Atlanta, GA.
Address all correspondence to Dr. Wolf.
This invited paper was submitted July 16, 1984,
and was accepted September 7, 1984.
314
trode placements and stimulation characteristics) and their effects on treatment
outcomes, and 3) neurophysiological
modes of action. Topics for future clinical study will also be discussed.
TRANSCUTANEOUS
ELECTRICAL NERVE
STIMULATION FOR ACUTE
PAIN
One of the most successful applications of TENS is for postoperative pain
control.1-11 Although treatment protocols vary between different studies, important treatment variables are fairly
consistent among these studies.1 Patients are generally provided with a preoperative exposure to TENS to choose
comfortable stimulation settings. Sterile
electrodes are placed adjacent to the incision in surgery, and TENS treatment
commences in the recovery room, with
the stimulation variables set at a previously established comfort level. Transcutaneous electrical nerve stimulation is
used continuously for the first 48 to 72
hours; the patient regulates the stimulus
intensity to suit his needs. Treatment
outcomes are measured not only by subjective pain report, but also by the type
and amount of pain medication requested by the patient. Incidences of
postoperative ileus and atelectasis, records on compliance with respiratory
therapy regimens, and length of inten-
sive care and hospital stay also provide
objective measures of the patient's response to TENS treatment.
Schomburg and Carter-Baker evaluated the analgesic effect of TENS on 75
postlaparotomy patients.2 In comparing
these patients with a matched control
group by retrospective chart observation, the authors found that patients
using TENS postoperatively required 56
percent fewer doses of pain medication
during the first five postoperative days
than did patients in the control group.
Patients receiving TENS were more mobile and participated in breathing exercises earlier than their control group
counterparts.
Ali et al studied the pulmonary function of 40 patients who had undergone
cholecystectomies.3 Fifteen patients
used TENS continuously for thefirst48
hours postoperatively and then on an
"as needed" basis. Another 15 patients
did not use TENS, and a third group of
10 patients used TENS units with the
batteries reversed so that no current was
delivered to the patient (sham TENS).
Spirometric evaluations of all patients
conducted on the third and fifth postoperative days indicated that patients
who were treated with TENS had significantly higher vital capacities and functional residual capacities than patients
receiving either sham TENS or no
TENS. Patients using TENS had a significantly decreased incidence of postPHYSICAL THERAPY
2. PRACTICE
operative pulmonary dysfunction and
complications. Patients in all groups required supplemental pain medications,
but those patients in the TENS group
required less pain medication than did
those not receiving actual TENS treatment.
Taylor and associates conducted a
similar study with patients who had
undergone abdominal surgery.4 Thirty
patients used actual TENS and 22 patients used sham units for one hour
every four hours for the first three postoperative days. Patients were permitted
to request pain medication after 30 minutes of TENS treatment if the treatment
did not adequately control pain.
Twenty-five patients served as a control
group. Taylor and associates noted that
patients receiving TENS or sham TENS
required less pain medication and ambulated earlier than did those patients
in the control group.4 The results highlighted the placebo potential of TENS
but may also be explained by the noncontinuous mode of TENS application.
Another study examined the analgesic
effect of TENS on patients who had
undergone upper abdominal surgery.6
The patients who used TENS for postoperative pain control required 30 times
less pain medication than did those in
the control group. Improved pulmonary
function, appetite, and ambulation indicated an earlier recovery for those patients who used TENS than for those
patients who did not. Because the report
of this study lacked information on
treatment protocol and technique, replicating or comparing these results with
similar studies is impossible.
Several investigators have studied the
efficacy of TENS for management of
postlaminectomy pain.7-9 In all these
studies, electrodes were placed parallel
to the incision, stimulation was set at
comfortable levels, TENS was used continuously for at least the first 24 to 48
hours, and the treatment was discontinued after that period at each patient's
request. The investigators all reported a
significant decrease in the strength and
amount of pain medication requested
by the patients using TENS in comparison with those patients not using
TENS. Solomon et al reported that
TENS appeared most effective in "drugnaive" patients, those who had not used
narcotics preoperatively for more than
two weeks in the six months before surgery.7 Furthermore, they noted that
poor pain relief was reported by drugVolume 65 / Number 3, March 1985
experienced patients, regardless of
whether TENS or narcotics were used.
This occurrence may suggest a crosstolerance between narcotics and TENS
and activation of a similar neural substrate to explain the analgesic effect of
both TENS and opioid derivative medications.
Richardson and Siquiera carefully recorded the stimulation settings used.8
They observed no correlation between
specific pulse widths, rates, or stimulus
intensities and the degree of pain relief
reported. Other investigators have corroborated this finding.12
Additional benefits of postoperative
pain management with TENS may be
realized by the postcesarean patient.
Nonnarcotic pain control by use of
TENS may facilitate earlier mother-infant bonding. Drug-induced side effects
such as nausea, drowsiness, and respiratory depression are limited. Narcotics
are not passed to the baby by breastfeeding. Pulmonary rehabilitation is facilitated and reduces the occurrence of
pulmonary complications in the
mother.10
Harvie cited rehabilitation benefits
when using TENS to control postoperative pain after knee surgery.11 He studied patients who had undergone total
knee replacements, synovectomies,
meniscectomies, arthrotomies, patchplasties, or fracture reductions. Electrodes placed over the medial and lateral
collateral ligaments provided the most
effective pain control. Narcotic use was
decreased by 75 to 100 percent. Recovery of quadriceps femoris muscle
strength and knee range of motion
(ROM) was facilitated. Four of seven
patients with total knee replacements
achieved 80 to 90 degrees of active knee
flexion by the sixth postoperative day;
the other three patients achieved the
same goal by the eighth postoperative
day. Earlier ambulation and decreased
length of hospital stay were also reported. Clearly, TENS for management
of postoperative knee pain is an important adjunct to a rehabilitation program.
Transcutaneous electrical nerve stimulation can also be applied for control
of acute dental pain.13, 14 Hansson and
Ekblom evaluated 62 patients admitted
to an emergency dental clinic with acute
pain secondary to pulpal inflammation,
apical periodontitis, or postoperative
pain after tooth extraction.13 Patients
were randomly assigned to one of three
groups: those receiving high frequency
TENS (100 Hz; n = 22); those receiving
low frequency TENS (2 Hz; n = 20);
and those receiving a placebo treatment
(batteries removed from the unit; n =
20). Electrodes were placed on the face
over the painful area. Stimulus intensity
was set to three times the sensory threshold for patients in the high frequency
group, and three to five times sensory
threshold for those receiving low frequency TENS. This latter group experienced muscular contractions associated with the higher intensity. Patients
used a visual analog scale to record their
pain intensity before, during, and after
treatment. Seven of 22 patients (31.8%)
in the high frequency group reported
pain relief of greater than 50 percent
after 30 minutes of treatment, compared
with 9 of 20 patients (45%) in the low
frequency group, and 2 of 20 (10%) in
the placebo group. Pain returned within
10 minutes after treatment in 4 of 7
patients in the high frequency group,
and in 2 of 9 patients in the low frequency group. The 2 patients in the
placebo group who reported initial relief
experienced longer lasting relief. Two
other patients in the high frequency
group and 2 in the low frequency group
reported complete pain relief after treatment. Differences in the analgesic effectiveness of TENS demonstrated between
the high and low frequency groups were
not significant. The effectiveness of
TENS for pain control, however, was
significantly greater when either experimental group was compared with the
placebo group. Pain control of longer
duration might have occurred if treatment duration could have been longer
than 30 minutes.
Transcutaneous electrical nerve stimulation is being used, especially outside
of the United States, to control acute
pain associated with labor and delivery.15, 16 Erkola et al evaluated 100 patients who used TENS for pain management during the first stage of labor.15
Electrodes were placed paravertebrally
at T10-11 and S2-4. Stimulus intensity
was set at a tolerable submotor threshold
and regulated by the patient. Thirty-one
percent of the patients reported good
pain relief, and 55 percent reported
moderate relief within one hour of initiating treatment. Details of the pain
rating procedure were not described. Patients using TENS, however, requested
a similar amount of pain medication
during labor in comparison with a control group who did not use TENS.
315
3. Jones reported that 82 percent of the
patients in labor using TENS had substantial relief of back labor pain and 71
percent had significant relief of abdominal labor pain during the first stage of
labor.16 Again, methods used to measure
pain were not described. During the second stage of labor, TENS was frequently
discontinued because it interfered with
the patient's controlled breathing and
pushing efforts. Transcutaneous electrical nerve stimulation also interfered
with continuous fetal monitoring. The
use of TENS did not affect the length of
labor or immediate postnatal health of
the infant.
Further investigation of the role of
TENS in the management of labor pain
is warranted with close attention paid to
application techniques and measurement of treatment outcome. Reduction
of the need for narcotics during labor
could contribute to the improved perinatal and postnatal health of the mother
and the improved respiratory and neurological status of the newborn child.
Methods of application for TENS to
control acute pain are summarized in
Table 1. All but one report provide specific electrode placements for particular
pain locations. Ranges are given most
frequently to describe stimulation settings used, and the frequency and duration of TENS treatment is reported.
The provision of application details in
recent literature allows more accurate
comparison and replication of clinical
research.
Table 2 summarizes the evaluation
tools used to assess TENS treatment
outcomes for acute pain management.
A variety of subjective pain rating scales
and recording of pain medication intake
were used most commonly to assess the
analgesic effect of TENS. In three studies, additional credence was given to
favorable treatment outcomes by use of
objective physical evaluations, such as
pulmonary function studies or joint
range-of-motion measurements. In addition to the patients' reports of pain,
objective evaluation procedures enhance the reliability and validity of these
clinical studies.
Recent literature has been favorable
on the efficacy of TENS for acute pain
control. The location and description of
acute pain is usually precise and allows
for use of a more specific treatment
approach. Homogeneous groups of patients (eg, those with postoperative pain)
and matched control groups are readily
available for evaluation. Treatment outcomes may be objectively measured in
terms of medication intake, respiratory
status, rehabilitation factors, and subjective pain ratings. These advantages are
not as readily available when studying
the management of chronic pain and
may explain the wide variation in response to TENS treatment among
chronic pain patients.
TRANSCUTANEOUS
ELECTRICAL NERVE
STIMULATION FOR CHRONIC
PAIN
Studies examining patients with
widely divergent diagnoses or symptom
complexes are not as prevalent in the
TENS literature today as they were several years ago. These studies can provide
valuable information in selecting which
diagnostic groups of patients respond
most favorably to TENS for pain relief.
Wolf and colleagues evaluated the responses to TENS of 114 patients with
chronic pain.12 Patients reported pain
secondary to peripheral neuropathy, peripheral nerve injury, radiculopathy, or
musculoskeletal trauma. Electrodes
were systematically placed at the painful
TABLE 1
Transcutaneous Electrical Nerve Stimulation Application Methods for Acute Pain
Primary Author
Diagnosis
Electrode Placement
Pulse Width
(µ see)
Pulse Rate
Intensity
(PPS)
0-90 V (comfort)
10-100
Frequency and Duration
of Treatments
Schomburg2
postlaparotomy
parallel to incision
120-340
Ali3
parallel to incision
128-200
10-100
0-135 mA (comfort)
Taylor4
Sodipo6
Solomon7
postcholecystectomy
postlaparotomy
postlaparotomy
postoperative
constant for first 48
hr, then as needed
constant for first 48 hr
80
40
comfort
60 min every 4 hr
Richardson8
postlaminectomy
parallel to incision
parallel to incision
1.0 cm parallel to
incision
5 cm parallel to
incision
Schuster9
postlaminectomy
Riley10
Harvie11
postcesarean
section
postoperative
knee pain
Hansson13
dental pain
2.5 cm parallel to
incision
above and below
incision
over medial and
lateral collateral
ligaments
over painful site
constant for first 48 hr
72.5240.0
8.7-240
0.2-38.5 mA
40-100
25-100
0-90 V
250-400
80-100
20-35 mA
comfort
labor pain
Jones16
labor pain
316
paraspinal T10L1, S2-S4
200
100
84
Erkola15
within first 20 hr postoperatively, for
3-12 days
constant for first
18-24 hr
constant, or 30 min
four times a day
2
2-3 times sensory
threshold or
3-5 times sensory
threshold
20-25 V (comfort)
comfort
30 min
30 min
during first stage of
labor
during first stage of
labor
PHYSICAL THERAPY
4. PRACTICE
TABLE 2
Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Acute Pain
Primary Author
Diagnosis
Subjective
Pain Rating
Pain Medication
Taken
Physical
Evaluations
Schomburg2
postlaparotomy
yes
yes
Ali3
no
yes
Taylor4
Sodipo6
Solomon7
Richardson8
postcholecystectomy
postlaparotomy
postlaparotomy
postoperative
postlaminectomy
yes
no
yes
yes
yes
yes
yes
yes
none
Schuster9
postlaminectomy
yes
yes
none
Riley10
postcesarean
section
postoperative
knee pain
yes
yes
none
no
yes
dental pain
labor pain
labor pain
yes
yes
yes
no
yes
yes
Other
knee range of motion, straight leg
raise, early ambulation
none
none
none
Harvie11
Hansson13
Erkola15
Jones 16
site or on related nerve roots or peripheral nerves. Stimulation variables were
set to evoke a strong but comfortable
sensation in the painful region, and exact electrical settings were recorded.
Treatments were conducted on an outpatient basis and were of 30- to 45minute duration. Patients rated their
pain intensity on a 10-cm line before,
during, and immediately after treatment. In addition, some patients completed the pain descriptor word list
found in the McGill Pain Questionnaire.17 Thirteen of 18 patients (72%)
with peripheral neuropathy, 6 of 21 patients (28.5%) with peripheral nerve injury, 8 of 36 patients (22%) with radicular pain, and 15 of 39 patients (38.4%)
with musculoskeletal pain reported
more than 60 percent relief of pain after
TENS treatment.12 In the peripheral
neuropathy group, patients with postherpetic neuralgia responded most
favorably to TENS. Patients with fewer
previous analgesic treatments, no surgical intervention, and limited narcotic
use responded more favorably than
those patients with numerous previous
treatments. We found no significant relationship between specific electrode
placements or stimulation settings and
treatment outcomes, but patients with
radiculopathy or peripheral nerve injury
responded better to higher intensity
stimulation. This observation was also
reported by Melzack in treating patients
with chronic low back pain.18 Follow-
Volume 65 / Number 3, March 1985
spirometry, arterial
blood gases
pulmonary functions
up evaluations on 25 patients who used
TENS at home for one month generally
indicated decreased benefits from treatment as time progressed. These decreased benefits may have been due to
reduced patient compliance when independent TENS application became a
requirement.
Another investigation studied 98 patients with back pain, headache, or a
variety of other pain symptoms.19 Patients used TENS at home, placing electrodes at the site of pain, and setting
stimulation intensity at a comfortable
level. Patients recorded their own subjective pain level before and after treatment. After 12 days of home treatment,
69 percent of the patients with low back
pain, 40 percent of those with headache
pain, and 60 percent of those with pain
from other sources reported more than
50 percent relief of pain. The authors
failed to describe stimulation settings,
pain-rating measures, and duration and
frequency of treatment; they also did
not control for a wide variation in application techniques based on patient
competence and compliance. Thus, this
study provided little valuable information on TENS for chronic pain control.
Santiesteban described the use of low
frequency TENS (2-4 Hz) for treatment
of spinal pain.20 Stimulus pulse width
was set at the maximum for the units
used, and intensity was set at 50 mA to
evoke a muscle contraction within pain
tolerance. Electrodes were placed 2.5 to
resumption of activities
postoperative
complication
resume ambulation
resume ambulation
length of hospital
stay
postoperative
complication
5 cm from the appropriate spinous process in a parallel or crossed configuration.
Distal acupuncture points were also
stimulated. Patients required less analgesic medication when TENS was used
to control pain.
Melzack and colleagues recently compared the analgesic effects of TENS and
massage in a double-blind study of 41
patients with chronic low back pain.21
Transcutaneous electrical nerve stimulation electrodes were placed in the center of the back and on the lateral thigh.
Low frequency stimulation (4-8 Hz)
with a strong but tolerable intensity was
applied. The massage was performed
with a suction cup apparatus. Treatment
was given two times a week for 30 minutes, for a maximum of 10 treatments.
Treatment outcomes were evaluated using both the present-pain intensity (PPI)
scale and the pain-rating index of the
McGill Pain Questionnaire.17 Bilateral
straight leg raising (SLR) and lumbosacral flexion were also measured.
Transcutaneous electrical nerve stimulation produced a significantly greater
improvement than massage in the painrating and the PPI scales and in the
bilateral SLR measures for these patients.21
Transcutaneous electrical nerve stimulation has been used with various degrees of success in the management of
arthritic pain. Taylor et al evaluated the
effect of TENS on osteoarthritic knee
pain.22 Patients used actual TENS or a
317
5. TABLE 3
Transcutaneous Electrical Nerve Stimulation Application Methods for Chronic Pain
Primary Author
Diagnosis
Wolf12
varied
Moore19
Electrode Placement
Pulse Width
(µ sec)
Pulse Rate
(pps)
Intensity
Frequency and Duration
of Treatments
100
50-100
submotor
threshold
30-45 min, 3-5
times a week
varied
site of pain, related
nerve roots, or
peripheral nerve
varied
midrange
10-100
or 1-4
comfort
Santiesteban20
spine pain
paravertebral
maximum
2-4
Melzack21
low back
pain
osteoarthritis
of knee
phantom
limb pain
nonunited
fracture
center of back and
lateral thigh
about knee
4-8
motor
threshold
(50 mA)
to tolerance
30-60 min daily or
as needed
30-60 min
comfort
comfort
stump or contralateral limb
over fracture site
in crossed pattern
100 or 2
peripheral
neuropa-
along nerve trunk
at site of pain
Taylor22
Winnem27
Kahn29
Gersh24
300
minimum
200
110
sensory
threshold
(less than
20 mA)
26-28 mA
30 min, 2 times a
week
30-60 min as
needed
15 min twice a day
30-60 min, 3-4
times a day
continuous, 8-10
hr a day
thy
placebo unit wired to produce various
sounds in a well-monitored home program. After two weeks of home treatment, patients were reevaluated and
sent home to use the other (TENS or
placebo) unit for another two weeks.
Patients were evaluated again and permitted to take home the most beneficial
unit for one more month of home treatment. Responses to treatment were evaluated by subjective pain rating, ambulation distance, and analgesic medication intake. The actual TENS provided
significantly more pain relief than did
the placebo unit in both subjective and
medication analyses. Patients reported
the greatest pain relief while wearing the
active TENS unit. Relief frequently
lasted for several hours after treatment
was completed. Several patients continued to use the TENS at home for several
months. They reported decreasing pain
relief over time, possibly because of increasing joint deterioration.
Transcutaneous electrical nerve stimulation may be an important adjunct in
the rehabilitation of arthritic patients,
particularly when joint replacement is
not possible. In patients with chronic
systemic diseases who may be receiving
a variety of pharmacologic and therapeutic treatments concurrently, the clinician must be alert, however, to adverse reactions to TENS, as reported by
Griffin and McClure.23
318
Patients with a variety of peripheral
neuropathic conditions including peripheral neuropathy,24 postherpetic neuralgia, peripheral nerve injury, reflex
sympathetic dystrophy,25 and Sudeck's
atrophy26 have all responded favorably
to TENS treatment. Transcutaneous
electrical nerve stimulation has also
proven effective in the management of
phantom limb pain27 and the distal
burning paresthesia associated with
Guillain-Barré syndrome.28
Kahn provided radiographic evidence
that TENS facilitated callous formation
and osseous bridging at sites of nonunited fractures in three patients.29
Transcutaneous electrical nerve stimulation was originally applied to control
pain in these patients for nonunited
fractures six months after injury. Electrodes were placed in various configurations to "sandwich" the fracture site.
Pulse width was set for the longest "on"
time, pulse rate was set at the lowest
available frequency, and stimulus intensity was set at the sensory threshold.
Increased callous formation was noticed
on radiographic examination after one
month of treatment in one patient and
after 10 weeks of treatment in the other
two patients.
Millea described another unusual application of TENS.30 A 50-year-old patient with an eight-year history of nonoperative abdominal pain and disten-
tion was relieved of this discomfort after
using TENS for five days. This relief
may be attributed to decreased sympathetic tone and increased gastric motility
associated with TENS application.31
Owens et al observed local vasodilation and skin temperature increases of
1°C when TENS was applied at the ulnar
groove and wrist in seven healthy subjects.31 Such evidence also may explain
the mechanism of pain relief in patients
with causalgia or reflex sympathetic dystrophy. Consistent sympathetic nervous
system responses, however, have not, as
yet, been recorded among a variety of
patients.25
Table 3 summarizes the application
procedures used for chronic pain control
with TENS. Significant effort has been
made by most investigators in recent
years to specify effective electrode placements and stimulating settings. Although specific pulse widths, rates, and
intensities are not always cited, most
reports provide a description of the sensory or motor responses elicited by
TENS during treatment. Treatment duration was usually 30 to 60 minutes, but
the frequency of treatment varied with
each study. Replication of clinical studies is facilitated when these procedures
are described in detail.
Perhaps the weakest aspect of the clinical study of TENS for chronic pain
control is evaluation of treatment outPHYSICAL THERAPY
6. PRACTICE
comes. Table 4 illustrates that most investigators still rely solely on the patient's report of pain to establish the
efficacy of TENS treatment. Often, the
pain-rating scale used by the patient is
not described in detail. The great variety
of pain symptoms, locations, previous
and concomitant treatments, medications, and psychological components associated with chronic pain make objective evaluation much more difficult
than in patients with acute pain. Use of
physical measures, such as joint motion,
strength, muscle girth, and participation
in functional activities, however, would
enhance the objective evaluation of the
efficacy of TENS for chronic pain control.
PREDICTING RESPONSE
TO TRANSCUTANEOUS
ELECTRICAL NERVE
STIMULATION TREATMENT
Successful use of TENS for pain control may be increased as more specific
patient evaluation and selection criteria
are established. Reynolds and associates
examined the predictive value of pain
questionnaires in selecting patients who
would be more likely to respond favorably to TENS treatment.32 Their evaluation indicated that older, retired patients, who had pain of less than one
year duration, who had undergone limited or no surgery, and who used nonnarcotic analgesics were more likely to
experience pain relief with TENS. Site
of injury, sensory deficit, and secondary
gain by financial compensation for injury did not affect response to treatment. The pain questionnaire, however,
seemed to have less predictive value for
TENS than for other treatment regimens.
In another study, Johansson et al suggested that patients with neurogenic
pain responded more favorably to
TENS than did patients with somatogenic or psychogenic pain.33 Patients
with pain in the extremities seemed to
derive more relief with TENS than patients with axial pain. The patient's age,
sex, and pain intensity did not relate to
his response to treatment.
Richardson and colleagues explained
how treatment with TENS could confirm a diagnosis of functional pain compared with organic pain.34 Many patients with suspected functional pain reported increased pain during and after
TENS treatment. Pain was relieved with
a saline injection in the majority of these
patients.
Mannheimer compiled a list of factors
that hinder, enhance, or restore the effectiveness of TENS for pain control.35
Among those factors that enhance
TENS effectiveness are careful, continuous patient evaluation for most effective electrode placement sites and stimulation settings; changing stimulation
modes and characteristics; gradually increasing patient tolerance to stronger
stimulation in the painful area; elec-
trode placement on motor points or superficial aspects of nerves; weaning patients from addictive medications before
treatment; and educating the patient in
the proper use of the modality for home
treatment. Incorporating these selection
and treatment criteria into treatment
protocols and recording which patients
most favorably respond to TENS will
increase the successful use of this modality in the future.
NEUROPHYSIOLOGICAL MODES
OF ACTION
Several years ago, the options available to explain the possible neurophysio l o g y mechanisms through which
TENS could affect pain perception were
limited.36 The prevailing explanation for
most pain attenuating interventions
cited the spinal gate concept developed
by Melzack and Wall in 1965.37 Briefly,
this notion took into account existing
electrophysiological data from animal
experiments that had demonstrated differential effects of collateral axons from
large diameter afferent fibers mediating
touch and pressure and from small diameter afferent fibers conveying nociceptive input upon interneurons within
the substantia gelatinosa (Fig. 1). These
interneurons could be facilitated
through predominantly large diameter
collateral afferent input and inhibited
through primarily collateral axons from
the small diameter system. In addition,
the interneuron was inhibitory onto the
TABLE 4
Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Chronic Pain
Primary Author
Diagnosis
Subjective
Pain Rating
Pain Medication
Taken
Physical
Evaluations
Wolf12
varied
McGill Pain
Questionnaire
no
none
Moore19
Santlesteban20
Melzack21
varied
spine pain
low back
pain
yes
no
no
yes
no
Taylor22
osteoarthritis
of knee
yes
yes
Winnem27
phantom
limb pain
nonunited
fracture
peripheral
neuropathy
yes
no
none
none
straight leg raise,
lumbosacral
range of motion
roentgenogram,
ambulation
distance
none
yes
no
roentgenogram
yes
no
none
Other
Kahn29
Gersh24
Volume 65 / Number 3, March 1985
McGill Pain
Questionnaire
resume functional
activities
319
7. Periphery
Spinal Cord
Lamina II & III
Spinal Cord
Lamina V
Fig. 1. Schematic diagram depicting the Melzack-Wall gate theory of pain. Open circles
represent facilitator/ synapses; closed circles indicate inhibitory synapses. Abbreviations SG
= substantia gelatinosa; T = transmission cells.
terminals of both afferent fiber classes.
Consequently, when large diameter
afferent fiber activation was of greater
frequency and intensity than smaller
diameter fiber input, the inhibitory
interneurons would be activated to
presynaptically inhibit transmission
centrally from both the noxious and
nonnoxious inputs. The gate would be
closed. Of course, the opposite effect
would predominate if greater transmission occurred through the smaller diameter system.
This gating theory was subjected to
considerable criticism because it conceptually failed to account for pain relief
among a variety of clinical conditions.
Nonetheless, the test of time has proven
that the framework for the theory has
formed the basis for several more contemporary explanations of pain alleviation through TENS. Specifically what
the Melzack-Wall model brought to the
attention of scientists and clinicians was
the recognition that pain perception
could be modulated somewhere within
the neuraxis if the appropriate stimuli
could be delivered and the appropriate
neural substrate on which such stimuli
might act could be found.
A spinal gate that conceptually follows the original model might incorporate conventional TENS (low intensity,
high frequency stimuli) to effect pain
reduction among patients with a diagnosis of postherpetic neuralgia. This disease process causes selective degeneration among large diameter peripheral
axons. The success with conventional
TENS may reside in the activation of
320
remaining large afferent fibers or those
in close proximity to the painful site but
which enter the neuraxis at the same or
nearby segments as the ongoing noxious
input.38 A similar explanation may be
appropriate to explain how pain following certain kinds of peripheral nerve
injury may respond to conventional
TENS.39
Recently, clinicians have recognized
that conventional TENS may not be the
most effective form of stimulation for
certain types of chronic pain. This
thought was promoted when Ericksson
and co-workers identified a large group
of patients with chronic pain who
showed further improvement in reduced
pain perception when conventional
TENS was supplemented by acupuncture-like TENS (low frequency, high intensity stimulation).40 This latter form
of stimulation showed effects that were
reversible through the administration of
the opioid antagonist, naloxone hydrochloride; this reversal suggests that the
effects of acupuncture-like TENS might
be mediated through an endogenous
opiate system within the neuraxis.41 Previously, Mayer and colleagues had demonstrated that the effectiveness of acupuncture was also reversed by naloxone
hydrochloride.42 These clinical findings
prompted a comprehensive search for
the neural substrates mediating the responsiveness of chronic pain patients to
high intensity cutaneous stimulation.
At the same time, a variety of opiate
receptors and numerous loci of endogenous opiates were being discovered in
many human and subhuman primate
studies.43 A logical marriage from this
exponentially increasing body of knowledge resided in establishing relationships
between neurophysiological and neurohistochemical studies on pain mechanisms and opiate substances, respectively. The mechanismfirstproposed by
Basbaum and Fields in 1978 served to
collate known histochemical and physiological data to explain how high intensity cutaneous electrical stimulation (for
example, acupuncture-like TENS, briefintense TENS, or burst trains of TENS)
might activate endogenous opiates to
alleviate pain.44
This modulatory mechanism is essentially a negative feedback loop that is
schematically illustrated in Figure 2.
Ongoing pain input and the discomfort
often associated with high intensity
TENS activate ascending pathways leading to conscious awareness of pain. Certain axons within the ascending system
are known to form a synapse within
medullary reticular formation nuclei,
and from these nuclei, this input is
transmitted to the periaqueductal gray
region of the midbrain (mesencephalon). This location is exceptionally endowed with high concentrations of endogenous opiates, and when it is activated, either through natural cutaneous
Central Nervous System
Fig. 2. Schematic diagram of negative feedback loop within the neuraxis activated by noxious
input.
PHYSICAL THERAPY
8. PRACTICE
stimulation, iontophoretically applied
morphine, or through direct stimulation, its efferent axons form a synapse
with nuclei (raphe magnus and reticularis magnocellularis) within the medulla oblongata. Output from these nuclear groups descends through the dorsolateral funiculus of the spinal cord to
make enkephalinergic synapses known
to inhibit the spinal transmission of Substance P, a polypeptide implicated as a
neurotransmitter between axons conveying noxious information.45 This last
neural interaction completes the negative feedback loop to modulate ongoing
or subsequent noxious input. For further details, please refer to the Pain:
Mechanism: B. Basic section within the
Bibliography.
Another mechanism that may account for some aspects of pain modulation with TENS involves what LeBars
et al have termed "diffuse noxious inhibitory controls," or DNIC.46 Within
this system, responses elicited through
continuous pain input to convergent
dorsal horn neurons may be suppressed
effectively by noxious or intense cutaneous stimulation, when it is applied
almost anywhere on the body surface.
Responses obtained through activity
within the small diameter afferent fiber
groups are inhibited, but nonnoxious
activation of the same convergent cells
or nonconvergent cells responsive to
only noxious stimuli remain unaffected.
Within animal models, spinalization
eliminates DNIC, thereby suggesting
that descending supraspinal influences
are required to activate this system. Furthermore, the DNIC mechanism is sensitive to naloxone hydrochloride; this
sensitivity indicates an endorphin link.47
Whether this linkage occurs at spinal or
supraspinal levels has yet to be determined. Also, definitive data to test the
validity of the DNIC model in man have
yet to be presented.
Nonetheless, the mechanisms described in this article form plausible explanations for the way in which high
intensity TENS might modulate pain
perception. Other mechanisms have
been proposed, but both the quantity
and quality of research led us to refrain
from addressing these in this article. Undoubtedly, as more data evolve and histochemical and electrophysiological
techniques gain sophistication, additional ways of speculating on or comprehending how TENS modulates pain
perception will be forthcoming.
Volume 65 / Number 3, March 1985
AREAS FOR FUTURE STUDY
To facilitate the continued effective
use of TENS for pain control, several
areas of study must be pursued. Patient
evaluation and selection criteria should
be validated and refined to increase successful treatment with TENS, particularly in patients who have chronic pain.
Specific electrode placements and stimulation characteristics must be evaluated in relation to specific disease entities to establish more effective treatment
protocols. Clinicians should continue to
evaluate the benefits of high versus low
frequency stimulation, auriculotherapy,48 and acupuncture point stimulation. Use of TENS for acute pain control should be expanded within areas
where it is apparently effective (eg, postoperative pain, labor and delivery pain,
and pain from acute injury48). Adverse
responses to treatment such as contact
dermatitis49, 50 should be reported so that
hypoallergenic materials can be developed in the manufacturing of electrodes
and conductive media, and so that patients at high risk for negative responses
to treatment may be screened.23 Ongoing evaluation of long-term use of TENS
by chronic pain patients may yield information on long-term effectiveness
and clarify the neurophysiology on
which treatment is based. The expanding body of knowledge resulting from
applied and basic research on neurochemical and physiological bases for
pain control must address the modus
operandi of TENS, taking into account
the stimulus characteristics applied
within experimental protocols and how
the relationship between stimulation
and response explains the efficacy of this
modality.
REFERENCES
1. Santiesteban AJ, Sanders BR: Establishing a
postsurgical TENS program. Phys Ther
60:789-791, 1980
2. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for postlaparotomy pain. Phys Ther 63:188-193, 1983
3. Ali J, Yaffe CS, Serrette C: The effect of transcutaneous electrical nerve stimulation on postoperative pain and pulmonary function. Surgery 89:507-512, 1981
4. Taylor AG, West BA, Simon B, et al: How
effective is TENS for acute pain? Am J Nurs
83:1171-1174, 1983
5. Bussey JG, Jackson A: TENS for Postsurgical
Analgesia. Read at the Meeting of the Biofeedback Society of Georgia, Atlanta, GA, November 16, 1982
6. Sodipo JOA, Adedeji SA, Olumide O: Postoperative pain relief by TENS. Am J Chin Med
8:190-194, 1980
7. Solomon RA, Viernstein MC, Long DM: Reduction of postoperative pain and narcotic use by
transcutaneous electrical nerve stimulation.
Surgery 87:142-146, 1980
8. Richardson RR, Siquiera EB: Transcutaneous
electrical neurostimulation in postlaminectomy
pain. Spine 5:361-365, 1980
9. Schuster GD, Infante MC: Pain relief after low
back surgery: The efficacy of TENS. Pain
8:299-302, 1980
10. Riley JE: The impact of TENS on the postcesarean patient. Journal of Obstetrics, Gynecology, and Neonatal Nursing 11:325-329,
1982
11. Harvie KW: A major advance in the control of
postoperative knee pain. Orthopedics 2:129131,1979
12. Wolf SL, Gersh MR, Rao VR: Examination of
electrode placements and stimulating parameters in treating chronic pain with conventional
transcutaneous electrical nerve stimulation.
Pain 11:37-47, 1981
13. Hansson P, Ekblom A: TENS as compared to
placebo TENS for relief of acute orofacial pain.
Pain 15:157-165, 1983
14. Pertovaara A, Kemppainen P, Johansson G, et
al: Dental analgesia produced by nonpainful
low frequency stimulation is not influenced by
stress or reversed by naloxone. Pain 13:379384,1982
15. Erkola R, Pikkola P, Kanto J: Transcutaneous
nerve stimulation for pain relief during labor: A
controlled study. Ann Chir Gynaecol 69:273277, 1980
16. Jones MCMH: Transcutaneous nerve stimulation in labor. Anaesthesia 35:372-375, 1980
17. Melzack R: The McGill Pain Questionnaire: Major properties and scoring methods. Pain
1:277-299, 1975
18. Melzack R: Prolonged relief of pain by brief
intense transcutaneous somatic stimulation.
Pain 1:357-373, 1975
19. Moore DE, Blacker HM: How effective is TENS
for chronic pain? Am J Nurs 83:1175-1177,
1983
20. Santiesteban AJ: The role of physical agents in
the treatment of spine pain. Clin Orthrop
179:24-30, 1983
21. Melzack R, Vetere P, Finch L: Transcutaneous
electrical nerve stimulation for low back pain:
A comparison of TENS and massage for pain
and range of motion. Phys Ther 63:489-493,
1983
22. Taylor P, Hallett M, Flaherty L: Treatment of
osteoarthritis of the knee with transcutaneous
electrical nerve stimulation. Pain 11:233-240,
1981
23. Griffin JW, McClure M: Adverse reactions to
transcutaneous electrical nerve stimulation in
a patient with rheumatoid arthritis. Phys Ther
61:354-355,1981
24. Gersh MR, Wolf SL, Rao VR: Evaluation of
transcutaneous electrical nerve stimulation for
pain relief in peripheral neuropathy: A clinical
documentation. Phys Ther 60:48-52,1980
25. Meyerson BA: Electrostimulation procedures,
effects, presumed rationale and possible
mechanisms. Advances in Pain Research and
Therapy 5:495-534, 1983
26. Bodenheim R, Bennett JH: Reversal of a Sudeck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation: A case
report. Phys Ther 63:1287-1288, 1983
27. Winnem MF, Amundsen T: Treatment of phantom limb pain with transcutaneous electrical
nerve stimulation. Pain 12:299-300, 1982
28. McCarthy JA, Zigenfus RW: Transcutaneous
electrical nerve stimulation: An adjunct in the
pain management of Guillain-Barre Syndrome.
Phys Ther 58:23-24, 1978
321
9. 29. Kahn J: Transcutaneous electrical nerve stim
ulation for nonunited fractures: A clinical re
port. Phys Ther 62:840-844, 1982
30. Millea TP: Transcutaneous electrical nerve
stimulation in the management of nonoperative
intra-abdominal pain: A case report. Phys Ther
63:1280-1282, 1983
31. Owens S, Atkinson ER, Lees DE: Thermo
graphic evidence of reduced sympathetic tone
with transcutaneous nerve stimulation. Anes
thesiology 50:62-65, 1979
32. Reynolds AC, Abram SE, Anderson RA, et al:
Chronic pain therapy with TENS: Predictive
value of questionnaires. Arch Phys Med Rehabil 64:311-313, 1983
33. Johansson F, Almay BGL, Von Knorring L, et
al: Predictors for the outcome of treatment
with high frequency transcutaneous electrical
nerve stimulation in patients with chronic pain.
Pain 9:55-61, 1980
34. Richardson RR, Arbit J, Siquiera EB, et al:
Transcutaneous electrical neurostimulation in
functional pain. Spine 6:185-188,1981
35. Mannheimer JS: Enhancing the Effectiveness
of TENS: Factors that Hinder, Enhance, and
Restore Effectiveness. Read at the National
36.
37.
38.
39.
40.
41.
42.
Pain Symposium, Indianapolis, IN, September
11-15,1982
Wolf SL: Perspectives on central nervous sys
tem responsiveness to transcutaneous electri
cal nerve stimulation. Phys Ther 58:14431449, 1978
Melzack R, Wall PD: Pain mechanisms: A new
theory. Science 150:971-979,1965
Nathan PW, Wall PD: Treatment of post her
petic neuralgia by prolonged electric stimula
tion. Br Med J 3:645-647, 1974
Meyer GA, Fields HL: Causalgia treated by
selective large fibre stimulation of peripheral
nerve. Brain 95:163-168, 1972
Ericksson MBE, Sjölund BH, Nielźen S: Long
term results of peripheral conditioning stimu
lation as an analgesic measure in chronic pain.
Pain 6:335-347, 1979
Sjölund BH, Ericksson MBE: The influence of
naloxone on analgesia produced by peripheral
conditioning stimulation. Brain Res 173:295301,1979
Mayer DJ, Price DD, Rafii A: Antagonism of
acupuncture analgesia in man by the narcotic
antagonic naloxone. Brain Res 121:368-372,
1977
43. Olson GA, Olson RD, Kastin AJ, et al: Endog
enous opiates: 1981. Peptides (Fayetteville)
3:1039-1073
44. Basbaum Al, Fields HL: Endogenous pain con
trol mechanisms: Review and hypothesis. Ann
Neurol 4:451-462, 1978
45. Basbaum Al: The generation and control of
pain. In Grossman RG, et al (eds): The Clinical
Neurosciences. New York, NY, Churchill Liv
ingstone Inc. 1983, vol 5, pp 301-324
46. LeBars D, Dickenson AH, Besson JM: Diffuse
noxious inhibitory control (DNIC): I. Effects on
dorsal horn convergent neurons in the rat. Pain
6:283-304, 1979
47. LeBars D, Chibour D, Kraus E, et al: Effect of
naloxone upon diffuse noxious inhibitory con
trols (DNIC) in the rat. Brain Res 204:387-402,
1981
48. Paris DL, Baynes F, Gucker B: Effects of the
Neuroprobe in the treatment of second-degree
ankle inversion sprains. Phys Ther 63:35-40,
1983
49. Bolton L: TENS electrode irritation. J Am Acad
Dermatol 8:134-135, 1983
50. Zugenman C: Dermatitis from TENS. J Am
Acad Dermatol 6:936-939,1982
BIBLIOGRAPHY
PAIN: TENS
1. Abram SE, Reynolds AC, Cusick FJ:
Failure of naloxone to reverse analgesia
from transcutaneous electrical stimula
tion in patients with chronic pain. Anesth
Analg 60:81-84, 1981
2. Berlant SR: Method of determining op
timal stimulation sites for transcutaneous
electrical nerve stimulation. Phys Ther
64:924-928, 1984
3. Besson JM, Chitour D, Dickenson AH,
et al: Involvement of endogenous opiates
in diffuse noxious inhibitory controls. J
Physiol (Lond) 300:26, 1980
4. Bodenheim R, Bennett JH: Reversal of
a Sudeck's atrophy by the adjunctive
use of transcutaneous electrical nerve
stimulation: A case report. Phys Ther
63:1287-1288,1983
5. Bohm E: Transcutaneous electrical
nerve stimulation in chronic pain after
peripheral nerve injury. Acta Neurochir
(Wien) 40:277-283, 1978
6. Butikofer R, Lawrence PD: Electrocutaneous nerve stimulation—II: Stimulus
waveform selection. IEEE Trans Biomed
Eng 26:69-75, 1979
7. Chung JM, Fang ZR, Cargill CL, et al:
Prolonged, naloxone-reversible inhibition
of the flexion reflex in the cat. Pain
15:35-53,1983
8. Doliber CM: Role of the physical thera
pist at pain treatment centers: A Survey.
Phys Ther 64:905-909, 1984
9. Fried T, Johnson R, McCracken W:
Transcutaneous electrical nerve stimu
322
10.
11.
12.
13.
14.
15.
16.
17.
18.
lation: Its role in the control of chronic
pain. Arch Phys Med Rehabil 65:228231,1984
Goldner JL, Nashold BS Jr, Hendrix PC:
Peripheral nerve electrical stimulation.
Clin Orthop 163:33-41, 1982
Hansson P, Ekblom A: Transcutaneous
electrical nerve stimulation (TENS) as
compared to placebo TENS for the relief
of acute oro-facial pain. Pain 15:157165,1983
Harvie KW: A major advance in the con
trol of postoperative knee pain. Or
thopedics 2:1-2, 1979
Hiedl P, Struppler A, Gessler M: TENSevoked long loop effects. Appl Neurophysiol 42:153-159, 1979
Hughes GS Jr, Lichstein PR, Whitlock D,
et al: Response of plasma beta-endorphins to transcutaneous electrical nerve
stimulation in healthy subjects. Phys
Ther 64:1062-1066,1984
Ignelzi RJ, Nyquist JK: Excitability
changes in peripheral nerve fibers follow
ing repetitive electrical stimulation: Impli
cations in pain modulation. J Neurosurg
51:824-830,1979
Janko M, Trontelj JV: Transcutaneous
electrical nerve stimulation: A microneurographic and perceptual study. Pain
9:219-230, 1980
Janko M, Trontelj JV: Flexion withdrawal
reflex as recorded from single human
biceps femoris motor neurones. Pain
15:167-176,1983
Jenkner FL, Schurfried F: Transdermal
transcutaneous electric nerve stimula
tion for pain: The search for an optimal
waveform. Appl Neurophysiol 44:330337, 1981
19. Johansson F, Almay BGL, Von Knorring
L, et al: Predictors for the outcome of
treatment with high frequency transcu
taneous electrical nerve stimulation in
patients with chronic pain. Pain 9:55-61,
1980
20. Krueger HC, Wong R, Jette DU: Opin
ions and comments: Use or misuse of
TENS with acupuncture. Phys Ther
64:1574-1576,1984
21. LeBars D, Besson JM: The spinal site of
action of morphine in pain relief: From
basic research to clinical applications.
Trends in Pharmacological Sciences
2:323-325, 1981
22. Lewis JW, Cannon JT, Lieberskind JC:
Opioid and nonopioid mechanisms of
stress analgesia. Science 208:623-625,
1980
23. Malow RM, Dougher MJ: A signal detec
tion analysis of the effects of transcuta
neous stimulation on pain. Psychosom
Med 41:101-108, 1979
24. Mannheimer C, Lund S, Carlsson C-A:
The effect of transcutaneous electrical
nerve stimulation (TENS) on joint pain in
patients with rheumatoid arthritis. Scand
J Rheumatol 7:13-16, 1978
25. Martin R, Salbaing J, Blaise G, et al:
Epidural morphine for postoperative pain
relief: A dose-response curve. J Anes
thesiology 56:423-426, 1982
26. McCarthy JA, Zigenfus RW: Transcuta
neous electrical nerve stimulation: An ad
junct in the pain management of GuillainBarre Syndrome: A case report. Phys
Ther 58:23-24,1978
PHYSICAL THERAPY
10. PRACTICE
27. McCreery DB, Bloedel JR: A critical ex
amination of the use of signal detection
theory in evaluating a putative analge
sic—transcutaneous electrical nerve
stimulation. Sensory Processes 2:3857, 1978
28. Melzack R: Recent concepts of pain. J
Med 13:147-160, 1982
29. Melzack R, Vetere P, Finch L: Transcu
taneous electrical nerve stimulation for
low back pain: A comparison of TENS
and massage for pain and range of mo
tion. Phys Ther 63:489-493, 1983
30. Meyer PG, Nashold BS, Peterson J: Di
agnosis of electric neurostimulating de
vice dysfunction. Appl Neurophysiol
42:352-364, 1979
31. Millea TP: Transcutaneous electrical
nerve stimulation in the management of
nonoperative intra-abdominal pain: A
case report. Phys Ther 63:1280-1282,
1983
32. Miller Jones CMH: Forum: Transcuta
neous nerve stimulation in labour. An
aesthesia 35:372-375, 1980
33. Nielźen S, Sjölund BH, Eriksson MBE:
Psychiatric factors influencing the treat
ment of pain with peripheral conditioning
stimulation. Pain 13:365-371, 1982
34. O'Brien WJ, Rutan FM, Sanborn C, et
al: Effect of transcutaneous electrical
nerve stimulation on human blood β-en
dorphin levels. Phys Ther 64:13671374, 1984
35. Ottoson D, Ekblom A, Hansson P: Vibra
tory stimulation for the relief of pain of
dental origin. Pain 10:37-45, 1981
36. Owens S, Atkinson ER, Lees DE: Ther
mographic evidence of reduced sympa
thetic tone with transcutaneous nerve
stimulation. Anesthesiology 50:62-65,
1979
37. Paris DL, Baynes F, Gucker B: Effects
of the neuroprobe in the treatment of
second-degree ankle inversion sprains.
Phys Ther 63:35-40, 1983
38. Pesschanski M, Guilbaud G, Gautron M:
Posterior intralaminar region in rat: Neu
ronal responses to noxious and nonnoxious cutaneous stimuli. Exp Neurol
73:226-238, 1981
39. Pike PMH: Transcutaneous electrical
stimulation: Its use in the management
of postoperative pain. Anaesthesia
33:165-171, 1978
40. Pomeranz B, Cheng R: Suppression of
noxious responses in single neurons of
cat spinal cord by electroacupuncture
and its reversal by the opiate antagonist
naloxone. Exp Neurol 64:327-341, 1979
41. Reynolds AC, Abram SE, Anderson RA,
et al: Chronic pain therapy with transcu
taneous electrical nerve stimulation: Pre
dictive value of questionnaires. Arch
Phys Med Rehabil 64:311-313, 1983
42. Richardson RR, Cerullo LJ: Transab
dominal neurostimulation in treatment of
neurogenic ileus. Appl Neurophysiol
42:375-382, 1979
43. Richardson RR, Cerullo LJ, Raimondi
AJ: Transabdominal neurostimulation in
the treatment of neurogenic ileus. Paper
read at Fifty-fifth Annual American Con
gress of Rehabilitation Medicine, New
Orleans, LA, November 12, 1978
Volume 65 / Number 3, March 1985
44. Salar G, Job I: Modification de L'Action
Antalgioue de L'Electrotérapie Transcutanee Aprés Traitement Avec Naloxone:
Note
préliminaire.
Neurochirurgie
24:415-417,1978
45. Salar G, Job I, Mingrino S, et al: Effect
of transcutaneous electrotherapy on
CSF beta-endorphin content in patients
without pain problems. Pain 10:169-
172, 1981
46. Schneider RJ: Low temperature painful
stimulus alters brain wave pattern of
transcutaneous electrical stimulus. Life
Sci 28:1269-1278, 1981
47. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for
postlaparotomy pain. Phys Ther 63:188193, 1983
48. Sebille A, Bondoux-Jahan M: Effects of
electric stimulation and previous nerve
injury on motor function recovery in rats.
Brain Res 193:562-565, 1980
49. Siegfried J, Haas HL: Inhibition by transcutaneous electrical stimulation of noxious heat elicited in human gasserian
ganglion. Eur Neurol 18:353-355, 1979
50. Stanley TH, Cazalaa JA, Atinault A, et
al: Transcutaneous cranial electrical
stimulation decreases narcotic requirements during neurolept anesthesia and
operation in man. Anesth Analg 61:863-
866, 1982
51. Stanley TH, Cazalaa JA, Limoge A, et al:
Transcutaneous cranial electrical stimulation increases the potency of nitrous
oxide in humans. Anesthesiology
57:293-297, 1982
52. Strax TE (Instructor): TENS-clinical applications. Paper read at the Fifty-fifth
Annual American Congress of Rehabilitation Medicine, New Orleans, LA, November 14, 1978
53. Talonen P, Malmivuo J, Baer G, et al:
Transcutaneous, dual channel phrenic
nerve stimulator for diaphragm pacing.
Med Biol Eng Comput 21:21-30, 1983
54. Taylor P, Hallett M, Flaherty L: Treatment of osteoarthritis of the knee with
transcutaneous electrical nerve stimulation. Pain 11:233-240, 1981
55. Trief PM: Chronic back pain: Tripartite
model of outcome. Arch Phys Med Rehabil 64:53-56, 1983
56. Urban BJ, Nashold BS: Combined epidural and peripheral nerve stimulation for
relief of pain. J Neurosurg 57:365-369,
1982
57. Wilier JC, Roby A, Boulu P, et al: Depressive effect of high frequency peripheral conditioning stimulation upon the nociceptive component of the human blink
reflex: Lack of naloxone effect. Brain Res
239:322-326, 1982
58. Wilier JC, Roby A, Boulu P, et al: Comparative effects of electroacupuncture
and transcutaneous nerve stimulation on
the human blink reflex. Pain 14:267-278,
1982
59. Wolf SL, Gersh MR, Rao VR: Examination of electrode placements and stimulating parameters in treating chronic pain
with conventional transcutaneous electrical nerve stimulation (TENS). Pain
11:37-47,1981
60. Wong RA, Jette DU: Changes in sympathetic tone associated with different
forms of transcutaneous electrical stimulation in healthy subjects. Phys Ther
64:478-482, 1984
61. Woolf CJ: Transcutaneous electrical
nerve stimulation and the reaction to experimental pain in human subjects. Pain
7:115-127,1979
62. Woolf CJ, Barrett GD, Mitchell D, et al:
Naloxone-reversible peripheral electroanalgesia in intact and spinal rats. Eur
J Pharmacol 45:311-314,1977
63. Wynne J, Parry L: Transcutaneous nerve
stimulation—an experimental study of
its analgesic action. Acupunct Electrother Res 4:195-202, 1979
64. Zoppi M, Francini F, Maresca C, et al:
Changes of cutaneous sensory thresholds induced by non-painful transcutaneous electrical nerve stimulation in normal subjects and in subjects with chronic
pain. J Neurol Neurosurg Psychiatry
44:708-717,1981
PAIN: MECHANISM
A. Clinical
1. Abram SE, Anderson RA: Using a pain
questionnaire to predict response to
steroid epidurals. Reg Anaesth 5:1114,1980
2. Abram SE, Anderson RA, MaitraD'Cruze AM: Factors predicting shortterm outcome of nerve blocks in the
management of chronic pain. Pain
10:323-330,1981
3. Amano K, Tanikawa T, Kawamura H,
et al: Endorphins and pain relief—further observations on electrical stimulation of the lateral part of the periaqueductal gray matter during rostral mesencephalic reticulotomy for pain relief.
Appl Neurophysiol 45:123-135, 1982
4. Besson JM, Guilbaud G, Abdelmoumene M, et al: Physiologie de la nociception. J Physiol (Paris) 78:7-107,
1982
5. Boivie J, Meyerson BA: A correlative
anatomical and clinical study of pain
suppression by deep brain stimulation.
Pain 13:113-126, 1982
6. Brucini M, Duranti R, Galletti R, et al:
Pain thresholds and electromyographic
features of periarticular muscles in patients with osteoarthritis of the knee.
Pain 10:57-66, 1981
7. Campbell JN: Examination of possible
mechanisms by which stimulation of
the spinal cord in man relieves pain.
Appl Neurophysiol 44:181-186,1981
8. Chao EYS: Justification of triaxial goniometer for the measurement of joint
rotation. J Biomech 13:989-1006,
1980
9. Clum GA, Luscumb RL, Scott L: Relaxation training and cognitive redirection
strategies in the treatment of acute
pain. Pain 12:175-183, 1982
10. Condes- Lara M, Calvo JM, FernandezGuardiola A: Habituation to bearable
experimental pain elicited by tooth pulp
electrical stimulation. Pain 11:185-200,
1981
323
11. 11. Cram JR, Stegar JC: EMG scanning in
the diagnosis of chronic pain. Biofeedback Self Regul 8:229-241, 1983
12. Doleys DM, Crocker M, Patton D: Response of patients with chronic pain to
exercise quotas. Phys Ther 62:11111114,1982
13. Dowling J: Autonomic indices and reactive pain reports on the McGill Pain
Questionnaire. Pain 14:387-392, 1982
14. Duranti R, Galletti R, Pantaleo T: Relationships between characteristics of
electrical stimulation, muscle pain and
blink responses in man. Electroencephalogr Clin Neurophysiol 55:637-644,
1983
15. Gehrig JD, Colpitts YH, Chapman CR:
Effects of local anesthetic infiltration on
brain potentials evoked by painful dental stimulation. Anesth Analg 60:779782, 1981
16. Gregg JM, Banerjee T, Ghia JN, et al:
Radiofrequency thermoneurolysis of
peripheral nerves for control of trigeminal neuralgia. Pain 5:231-243, 1978
17. Hiedl P, Struppler A, Gessler M: Local
analgesia by percutaneous electrical
stimulation of sensory nerves. Pain
7:129-134,1979
18. Hosobuchi Y: The majority of unmyelinated afferent axons in human ventral
roots probably conduct pain. Pain
8:167-180,1980
19. Howe JF: Phantom limb pain—a reafferentation syndrome. Pain 15:101107, 1983
20. Kaplan RM, Metzger G, Jablecki C:
Brief cognitive and relaxation training
increases tolerance for a painful clinical
electromyographic examination. Psychosom Med 45:155-162, 1983
21. King RB: Principles of pain management: A short review. J Neurosurg
50:554-559, 1979
22. Krivoy WA, Couch JR, Stewart JM, et
al: Modulation of cat monosynaptic reflexes by substance P. Brain Res
202:365-372, 1980
23. Laemle LK: Neuronal populations of the
human periaqueductal gray, nucleus lateralis. J Comp Neurol 186:93-107,
1979
24. Laitinen LV: Inhibition of cutaneous nociception by deep musculoskeletal
pain: A clinical observation. Pain
13:373-377, 1982
25. Levine JD, Gordon NC, Fields HL: Naloxone dose dependently produces analgesia and hyperalgesia in postoperative pain. Nature 278:740-741, 1979
26. Levine JD, Gordon NC, Smith R, et al:
Post-operative pain: Effect of extent of
injury and attention. Brain Res
234:500-504, 1982
27. Levine JD, Lane ST, Gordon NC, et al:
A spinal opioid synapse mediates the
interaction of spinal and brain stem
sites in morphine analgesia. Brain Res
236:85-91,1982
28. Lindblom U, Tegner R: Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients. Pain 7:65-68, 1979
29. Long DM, Erickson D, Campbell J, et
al: Electrical stimulation of the spinal
cord and peripheral nerves for pain con-
324
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
trol. Appl Neurophysiol 44:207-217,
1981
Malow RM, Olson RE: Changes in pain
perception after treatment for chronic
pain. Pain 11:65-72, 1981
Markoff RA, Ryan P, Young T: Endorphins and mood changes in long-distance running. Med Sci Sports Exerc
14:11-15,1982
Marsland AR, Weekes JWN, Atkinson
RL, et al: Phantom limb pain: A case
for beta blockers? Pain 12:295-297,
1982
Mather L, Mackie J: The incidence of
postoperative pain in children. Pain
15:271-282,1983
Meglio M, Cioni B, Del Lago A, et al:
Pain control and improvement of peripheral blood flow following epidural
spinal cord stimulation. J Neurosurg
54:821-823, 1981
Melzack R, Loeser JD: Phantom body
pain in paraplegics: Evidence for a central "Pattern Generating Mechanism"
for pain. Pain 4:195-210, 1978
Meyer RA, Campbell JN: Myelinated
nociceptive afferents account for the
hyperalgesia that follows a burn to the
hand. Science 213:1527-1529, 1981
Mills KR, Newham DJ, Edwards RHT:
Force, contraction frequency and energy metabolism as determinants of ischaemic muscle pain. Pain 14:149154, 1982
Neumann PB, Henriksen H, Grosman
N, et al: Plasma morphine concentrations during chronic oral administration
in patients with cancer pain. Pain
13:247-252, 1982
Noordenbos W, Wall PD: Implications
of the failure of nerve resection and
graft to cure chronic pain produced by
nerve lesions. J Neurol Neurosurg Psychiatry 44:1068-1073, 1981
Pertovaara A, Kemppainen P, Johansson G, et al: Ischemic pain nonsegmentally produces a predominant reduction
of pain and thermal sensitivity in man:
A selective role for endogenous
opioids. Brain Res 251:83-92, 1982
Pertovaara A: Modification of human
pain threshold by specific tactile receptors. Acta Physiol Scand 107:339-341,
1979
Ray CD: Spinal epidural electrical stimulation for pain control: Practical details
and results. Appl Neurophysiol 44:194-
206, 1981
43. Ready LB, Sarkis E, Turner JA: Selfreported vs actual use of medications
in chronic pain patients. Pain 12:285-
294, 1982
44. Richelson E: Spinal opiate administration for chronic pain: A major advance
in therapy. Mayo Clin Proc 56:1-3,
1981
45. Roby A, Bussel B, Wilier JC: Morphine
reinforces post-discharge inhibition of
a-motoneurons in man. Brain Res
222:209-212, 1981
46. Rosenfeld JP, Pickrel C, Bronton JG:
Analgesia for orofacial nociception produced by morphine microinjection into
the spinal trigeminal complex. Pain
15:145-155, 1983
47. Salter M, Brooke RI, Merskey H, et al:
Is the temporo-mandibular pain and
dysfunction syndrome a disorder of the
mind? Pain 17:151-166, 1983
48. Schull J, Kaplan H: Naloxone can alter
experimental pain and mood in humans.
Physiological
Psychology
9:245-250, 1981
49. Scott DS, Gregg JM: Myofascial pain
of the temporo-mandibular joint: A review of the behavioral-relaxation therapies. Pain 9:231-241, 1980
50. Simone DA, Bodnar RJ: Modulation of
antinociceptive responses following tail
pinch stress. Life Sci 30:719-729,
1982
51. Speculand B, Goss AN, Hughes A, et
al: Temporo-mandibular joint dysfunction: Pain and illness behavior. Pain
17:139-150,1983
52. Turner JA, Calsyn DA, Fordyce WE, et
al: Drug utilization patterns in chronic
pain patients. Pain 12:357-363, 1982
53. Varni JW: Self-regulation techniques in
the management of chronic arthritic
pain in hemophilia. Behavior Therapy
12:185-194, 1981
54. Varni JW: Behavioral medicine in hemophilia arthritic pain management: Two
case studies. Arch Phys Med Rehabil
62:183-187, 1981
55. Varni JW, Bessman CA, Russo DC, et
al: Behavioral management of chronic
pain in children: Case study. Arch Phys
Med Rehabil 61:375-379, 1980
56. Wilier JC, Albe-Fessard D: Further
studies on the role of afferent input
from relatively large diameter fibers in
transmission of nociceptive messages
in humans. Brain Res 278:318-321,
1983
57. Wilier JC, Boureau F, Albe-Fessard D:
Human nociceptive reactions of spatial
summation of afferent input from relatively large diameter fibers. Brain Res
201:465-470, 1980
58. Wilier JC, Boureau F, Albe-Fessard D:
Supraspinal influences on nociceptive
flexion reflex and pain sensation in
man. Brain Res 179:61-68, 1979
59. Wolf SL: Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation.
Phys Ther 58:1443-1449, 1978
60. Woolf CJ: Evidence for a central component of post-injury pain hypersensitivity. Nature 306:686-688, 1983
PAIN: MECHANISM
B. Basic
1. Abbott FV, Melzack R, Samuel C: Morphine analgesia in the tail-flick and formalin pain tests is mediated by different
neural systems. Exp Neurol 75:644651,1982
2. Abols IA, Basbaum AI:Afferent connections of the rostral medulla of the cat:
A neural substrate for midbrain-medullary interactions in the modulation of
pain. J Comp Neurol 201:285-297,
1981
3. Andersen E, Nachum D: An ascending
serotonergic pain modulation pathway
from the dorsal raphe nucleus to the
PHYSICAL THERAPY
12. PRACTICE
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
parafasciculans nucleus of the thalamus. Brain Res 269:57-67, 1983
Andersen RK, Lund JP, Puil E: Excitation and inhibition of neurons in the
trigeminal nucleus caudalis following
periaqueductal gray stimulation. Can J
Physiol Pharmacol 56:157-161, 1978
Azami J, Llewelyn MB, Roberts MHT:
The contribution of nucleus reticularis
paragigantocellularis
and
nucleus
raphe magnus to the analgesia produced by systemically administered
morphine, investigated with the microinjection technique. Pain 12:229246, 1982
Basbaum Al, Clanton CH, Fields HL:
Three bulbospinal pathways from the
rostral medulla of the cat: An autoradiographic study of pain modulating systems. J Comp Neurol 178:209-224,
1978
Basbaum Al, Fields HL: Endogenous
pain control mechanisms: Review and
hypothesis. Ann Neurol 4:451-462,
1978
Beal JA, Bicknell HR: Primary afferent
distribution pattern in the marginal zone
(Lamina I) of adult monkey and cat
lumbosacral spinal cord. J Compar
Neurol 202:255-263, 1981
Beal JA, Penny JE, Bicknell HR: Structural diversity of marginal (Lamina I)
neurons in the adult monkey (Macaca
mulatta) lumbosacral spinal cord: A
Golgi study. J Compar Neurol
202:237-254, 1981
Behbehani MM, Fields HL: Evidence
that an excitatory connection between
the periaqueductal gray and nucleus
raphe magnus mediates stimulation
produced analgesia. Brain Res 170:8593,1979
Behbehani MM, Pomeroy SL: Effect of
morphine injected in periaqueductal
gray on the activity of single units in
nucleus raphe magnus of the rat. Brain
Res 149:266-269, 1978
Benabid AL, Henriken SJ, McGinty JF,
et al: Thalamic nucleus ventro-posterolateralis inhibits nucleus parafasciculans response to noxious stimuli
through a non-opioid pathway. Brain
Res 280:217-231, 1983
Bennett GJ, Mayer DJ: Inhibition of
spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray
matter. Brain Res 172:243-257, 1979
Biedenbach MA, Van Hassel HJ, Brown
AC: Tooth pulp-driven neurons in somatosensory cortex of primates: Role
in pain mechanisms including a review
of the literature. Pain 7:31-50, 1979
Brinkhus HB, Carstens E, Zimmermann
M: Encoding of graded noxious skin
heating by neurons in posterior thalamus and adjacent areas in the cat. Neurosci Lett 15:37-42, 1979
Brinkhus HB, Zimmermann M: Characteristics of spinal dorsal horn neurons after partial chronic deafferentation by dorsal root transection. Pain
15:221-236, 1983
Brushart TM, Henry EW, Mesulam MM: Reorganization of muscle afferent
projections accompanies peripheral
Volume 65 / Number 3, March 1985
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
nerve regeneration.
Neuroscience
6:2053-2061,1981
Burgoin S, Oliveras JL, Bruxelle J, et
al: Electrical stimulation of the nucleus
raphe magnus in the rat. Effects on 5HT metabolism in the spinal cord. Brain
Res 194:377-389, 1980
Cannon JT, Lewis JW, Weinberg VE,
et al: Evidence for the independence of
brainstem mechanisms mediating analgesia induced by morphine and two
forms of stress. Brain Res 269:231236, 1983
Cannon JT, Prieto GJ, Lee A, et al:
Evidence for opioid and non-opioid
forms of stimulation-produced analgesia in the rat. Brain Res 243:315-321,
1982
Carstens E: Inhibition of spinal dorsal
horn neuronal responses to noxious
skin heating by medial hypothalamic
stimulation in the cat. J Neurophysiol
48:808-822, 1982
Carstens E, Fraunhoffer M, Suberg SN:
Inhibition of spinal dorsal horn neuronal
responses to noxious skin heating by
lateral hypothalamic stimulation in the
cat. J Neurophysiol 50:192-204, 1983
Carstens E, Fraunhoffer M, Zimmermann M: Serotonergic mediation of
descending inhibition from midbrain
periaqueductal gray, but not reticular
formation, of spinal nociceptive transmission in the cat. Pain 10:149-167,
1981
Carstens E, Klumpp D, Zimmermann
M: Differential inhibitory effects of medial and lateral midbrain stimulation on
spinal neuronal discharges to noxious
skin heating in the cat. J Neurophysiol
43:332-342, 1980
Carstens E, Klumpp D, Zimmermann
M: The opiate antagonist, naloxone,
does not affect descending inhibition
from midbrain of nociceptive spinal neuronal discharges in the cat. Neurosci
Lett 11:323-327, 1979
Carstens E, Klumpp D, Zimmermann
M: Time course and effective sites for
inhibition from midbrain periaqueductal
gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat.
Exp Brain Res 38:425-430, 1980
Carstens E, Yokota T, Zimmermann M:
Inhibition of spinal neuronal responses
to noxious skin heating by stimulation
of mesencephalic periaqueductal gray
in the cat. J Neurophysiol 42:558-568,
1979
Carstens E, Zimmermann M: The opiate antagonist naloxone does not
consistently block inhibition of spinal
nociceptive transmission produced by
stimulation in lateral midbrain reticular
formation of the cat. Neurosci Lett
20:335-339, 1980
Casey KL, Morrow TJ: Ventral posterior thalamic neurons differentially responsive to noxious stimulation of the
awake monkey. Science 221:675-677,
1983
Cervero F, Iggo A, Molony V: An electrophysiological study of neurones in
the substantia gelatinosa rolandi of the
cat's spinal cord. J Exp Physiol
64:297-314, 1979
31. Cervero F, Iggo A, Molony V: Segmental and intersegmental organization of
neurones in the substantia gelatinosa
rolandi of the cat's spinal cord. J Exp
Physiol 64:315-326, 1979
32. Cervero F, Molony V, Iggo A: Supraspinal linkage of substantia gelatinosa
neurones: Effects of descending impulses. Brain Res 175:351-355, 1979
33. Chan SHH: Central neurotransmitter
systems in the morphine suppression
of jaw-opening reflex in rabbits: The
dopaminergic system. Exp Neurol
65:526-534, 1979
34. Chan SHH, Lai Y-Y: Effects of aging on
pain responses and analgesic efficacy
of morphine and clonidine in rats. Exp
Neurol 75:112-119, 1982
35. Cheh G, Sykova E, Vyklicky L: Neurones activated from nociceptors in the
spinal cord of the frog. Neurosci Lett
16:257-262, 1980
36. Colpaert FC, Niemegeers CJE, Janssen PA: Nociceptive stimulation prevents development of tolerance to narcotic analgesia. Eur J Pharmacol
49:335-336, 1978
37. Dennis SG, Choiniere M, Melzack R:
Stimulation-produced analgesia in rats:
Assessment by two pain tests and correlation with self-stimulation. Exp Neurol 68:295-309, 1980
38. Devor M, Govrin-Lippmann R: Axoplasmic transport block reduces ectopic impulse generation in injured peripheral nerves. Pain 16:73-85, 1983
39. Devor M, Wall PD: Plasticity in the
spinal cord sensory map following peripheral nerve injury in rats. J Neurosci
1:679-684,1981
40. Dickenson AH: The inhibitory effects of
thalamic stimulation on the spinal transmission of nociceptive information in
the rat. Pain 17:213-224, 1983
41. Dickenson AH, Oliveras JL, Besson
JM: Role of the nucleus raphe magnus
in opiate analgesia as studied by the
microinjection technique in the rat.
Brain Res 170:95-111, 1979
42. Dickenson AH, Rivot JP, Chaouch A,
et al: Diffuse noxious inhibitory controls
(DNIC) in the rat with or without pCPA
pretreatment. Brain Res 216:313-321,
1981
43. Dohi S, Toyooka H, Kitahata LM: Effects of morphine sulfate on dorsalhorn neuronal responses to graded
noxious thermal stimulation in the decerebrate cat. Anesthesiology 51:408413,1979
44. Dong WK, Ryu H, Wagman IH: Nociceptive responses of neurons in medial
thalamus and their relationship to spinothalamic pathways. J Neurophysiol
41:1592-1613.1978
45. Dostrovsky JO: Raphe and peraqueductal gray induced suppression of
non-nociceptive neuronal responses in
the dorsal column nuclei and trigeminal
sub-nucleus caudalis. Brain Res
200:184-189,1980
46. Dostrovsky JO, Shah Y, Gray BG: Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation.
325
13. 47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
326
II. Effects on medullary dorsal horn nociceptive and nonnociceptive neurons.
J Neurophysiology 49:948-960, 1983
Dubner R, Bennett GJ: Spinal and trigeminal mechanisms of nociception.
Ann Rev Neurosci 6:381-418, 1983
Dubuisson D, Wall PD: Medullary raphe
influences on units in laminae 1 and 2
of cat spinal cord. J Physiol (Paris)
300:33, 1979
Edmeads J: The physiology of pain: A
review.
Neuropsychopharmacology
and Biological Psychiatry 7:413-419,
1983
Emmers R: Dual alterations of thalamic
nociceptive activity by stimulation on
the periaqueductal gray matter. Exp
Neurol 65:186-201, 1979
Fields HL, Anderson SD: Evidence that
raphe-spinal neurons mediate opiate
and midbrain stimulation-produced analgesias. Pain 5:333-349, 1978
Fields HL, Basbaum Al: Brainstem control of spinal pain-transmission neurons. Annu Rev Physiol 40:217-248,
1978
Fitzgerald M, Wall PD: The laminar organization of dorsal horn cells responding to peripheral C-fibre stimulation.
Exp Brain Res 41:36-44, 1980
Fitzgerald M, Woolf CJ: Differential
laminar response of dorsal horn neurones to naloxone in the spinal rat. J
Physiol (Lond) 305:98, 1980
Fox JE, Wolstencroft JH: The reduced
responsiveness of neurones in nucleus
reticularis gigantocellularis following
their excitation by peripheral nerve
stimulation. J Physiol (Lond) 258:687704, 1976
Gebhart GF: Opiate and opioid peptide
effects on brain stem neurons: Relevance to nociception and antinociceptive mechanisms. Pain 12:93-140,
1982
Gebhart GF, Toleikis JR: An evaluation
of stimulation-produced analgesia in
the cat. Exp Neurol 626:570-679,
1978
Gebhart GF, Sandkuhler J, Thalhammer JG, et al: Inhibition of spinal nociceptive information by stimulation in
midbrain of the cat is blocked by lidocaine microinjected in nucleus raphe
magnus and medullary reticular formation. J Neurophysiol 50:1446-1459,
1983
Gerhart KD, Wilcox TK, Chung JM, et
al: Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial
brain stem. J Neurophysiol 45:121136, 1981
Gerhart KD, Yezierski RP, Fang ZR, et
al: Inhibition of primate spinothalamic
tract neurons by stimulation in ventral
posterior lateral (VP1c) thalamic nucleus: Possible mechanisms. J Neurophysiol 49:406-423, 1983
Gerhart KD, Yezierski RP, Wilcox TK,
et al: Inhibition of primate spinothalamic
tract neurons by stimulation in periaqueductal gray or adjacent midbrain reticular formation. J Neurophysiol
51:450-466, 1984
62. Giesler GJ, Menetrey D, Basbaum AI:
Differential origins of spinothalamic
tract projections to medial and lateral
thalamus in the rat. J Comp Neurol
184:107-125, 1979
63. Gray BG, Dostrovsky JO: Descending
inhibitory influences from periaqueductal gray, nucleus raphe magnus,
and adjacent reticular formation. I. Effects on lumbar spinal cord nociceptive
and nonnociceptive neurons. J Neurophysiol 49:943-947, 1983
64. Haber LH, Martin RF, Chung JM, et al:
Inhibition and excitation of primate spinothalamic tract neurons by stimulation
in region of nucleus reticularis gigantocellularis. J Neurophysiol 43:15781593,1980
65. Haber LH, Moore BD, Willis WD: Electrophysiological response properties of
spinoreticular neurons in the monkey.
J Comp Neurol 207:75-84, 1982
66. Hammond DL, Proudfit HK: Effects of
locus coeruleus lesions on morphineinduced antinociception. Brain Res
- 188:79-91, 1980
67. Hanaoka K, Ohtani M, Toyooka H, et
al: The relative contribution of direct
and supraspinal descending effects
upon spinal mechanisms of morphine
analgesia. J Pharmacol Exp Ther
207:476-484, 1978
68. Hardy SGP, Haigler HJ, Leichnetz GR:
Paralemniscal reticular formation: Response of cells to a noxious stimulus.
Brain Res 267:217-223, 1983
69. Hayes RL, Bennett GJ, Newlon PG, et
al: Behavioral and physiological studies
of non-narcotic analgesia in the rat elicited by certain environmental stimuli.
Brain Res 155:69-90, 1978
70. Hayes RL, Price DD, Ruda M, et al:
Suppression of nociceptive responses
in the primate by electrical stimulation
of the brain or morphine administration:
Behavioral and electrophysiological
comparisons. Brain Res 167:417-421,
1979
71. Heinricher MM, Rosenfeld P: Microinjection of morphine into nucleus reticularis paragigantocellularis of the rat
suppresses spontaneous activity of nucleus raphe magnus neurons. Brain
Res 272:382-386, 1983
72. Hentall ID, Fields HL: Potentiation of
transmission from C-fibers to dorsal
horn neurons after tetanus of peripheral
nerve. Brain Res 189:540-543, 1980
73. Hentall ID, Fields HL: Segmental and
descending influences on intraspinal
thresholds of single C-fibers. J Neurophysiol 42:1527-1537, 1979
74. Hill RG, Morris R: Responses of nucleus reticularis ventralis neurones of
the rat to noxious stimuli and to electrical stimulation of the periaqueductal
gray and raphe dorsalis. J Physiol
(Lond) 301:38-39, 1979
75. Honda CN, Mense S, Perl ER: Neurons
in ventrobasal region of cat thalamus
selectively responsive to noxious mechanical stimulation. J Neurophysiol
49:662-673, 1983
76. Iggo A: Peripheral and spinal "pain"
mechanisms and their modulation. Ad-
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
vances in Pain Research and Therapy
1:381-394,1976
Jordan LM, Kenshalo DR, Martin RF,
et al: Two populations of spinothalamic
tract neurons with opposite responses
to 5-hydroxytryptamine. Brain Res
164:342-346, 1979
Jurna I: Effect of stimulation in the periaqueductal gray matter on activity in
ascending axons of the rat spinal cord:
Selective inhibition of activity evoked
by afferent A-delta and C-fibre stimulation and failure of naloxone to reduce
inhibition. Brain Res 196:33-42, 1980
Keith CK, Ebner TJ, Bloedel JR: Effects
of periaqueductal gray and raphe magnus stimulation on the responses of
spinocervical, and other ascending projection neurons to non-noxious inputs.
Brain Res 291:29-37, 1984
Kerr FWL, Wilson PR: Pain. Annu Rev
Neurosci 1:83-102,1978
KrausE, Besson JM, LeBars D: Behavioral model for diffuse noxious inhibitory
controls (DNIC): Potentiation by 5-hydroxytryptophan. Brain Res 231:461465, 1982
Kraus E, LeBars D, Besson JM: Behavioral confirmation of "Diffuse Noxious
Inhibitory Controls" (DNIC) and evidence for a role of endogenous opiates.
Brain Res 206:495-499, 1981
Kumazawa T, Perl ER: Excitation of
marginal and substantia gelatinosa
neurons in the primate spinal cord: Indications of their place in dorsal horn
functional organization. J Comp Neurol
177:417-434, 1978
LaMotte RH: Information processing in
cutaneous nociceptors in relation to
sensations of pain. Fed Proc 42;25482552, 1983
LeBars D, Chitour D, Clot AM: The
encoding of thermal stimuli by diffuse
noxious inhibitory controls (DNIC).
Brain Res 230:394-399, 1981
LeBars D, Dickenson AH, Besson JM:
Diffuse noxious inhibitory controls
(DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain
6:283-304, 1979
LeBars D, Dickenson AH, Besson JM:
Diffuse noxious inhibitory controls
(DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications. Pain
6:305-327, 1979
LeBars D, Dickenson AH, Besson JM:
Microinjection of morphine within nucleus raphe magnus and dorsal horn
neurone activities related to nociception in the rat. Brain Res 189:467-481,
1980
LeBars D, Guilbaud G, Chitour D, et al:
Does systemic morphine increase descending inhibitory contrpls of dorsal
horn neurones involved in nociception?
Brain Res 202:223-228, 1980
Levine JD, Gordon NC, Fields HL: Naloxone fails to antagonize nitrous oxide
analgesia for clinical pain. Pain 13:165170, 1982
Levitt M: The bilaterally symmetrical
deafferentation syndrome in macaques
after bilateral spinal lesions: Evidence
PHYSICAL THERAPY
14. PRACTICE
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
for dysesthesias resulting from brain
foci and considerations of spinal pain
pathways. Pain 16:167-184, 1983
Lewis JW, Terman GW, Watkins LR,
et al: Opioid and non-opioid mechanisms of footshock-induced analgesia:
Role of the spinal dorsolateral funiculus. Brain Res 267:139-144, 1983
Liu RPC: Laminar origins of spinal projection neurons to the periaqueductal
gray of the rat. Brain Res 264:118122,1983
Lovick TA, Wolstencroft JH: Responses of medial reticular neurones to
tooth pulp stimulation: Evidence for a
monosynaptic input. J Physiol (Lond)
292:40-41,1979
Maciewicz R, Sandrew BB, Phipps BS,
et al: Pontomedullary raphe neurons:
Intracellular responses to central and
peripheral electrical stimulation. Brain
Res 293:17-33, 1984
Matsumiya T, Berry JN, Bell JA: The
effect of intraspinal microinjection of
dopamine on the C-fiber reflex in the
acute decerebrate spinal cat. Life Sci
1153-1158, 1979
McMahon SB, Wall PD: A system of rat
spinal cord lamina 1 cells projecting
through the contralateral dorsolateral
funiculus. J Comp Neurol 214:217223, 1983
Menetrey D, Chaouch A, Besson JM:
Responses of spinal cord dorsal horn
neurones to non-noxious and noxious
cutaneous temperature changes in the
spinal rat. Pain 6:265-282, 1979
Meyer RA, Campbell JN: Evidence for
two distinct classes of unmyelinated
nociceptive afferents in monkey. Brain
Res 224:149-152, 1981
Milne RJ, Foreman RD, Willis WD: Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (Stilling's Nucleus) to proprioceptive input from the tail. Brain
Res 234:227-236, 1982
Miyakawa H, Okuda K, Shima K, et al:
Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship
to the effects of morphine and pentazocine. Tohoku J Exp Med 137:11-19,
1982
Mohrland JS, Gebhart GF: Effects of
focal electrical stimulation and morphine microinjection in the periaqueductal gray of the rat mesencephalon
on neuronal activity in the medullary
reticular formation. Brain Res 201:2337,1980
Mohrland JS, McManus DQ, Gebhart
GF: Lesions in nucleus reticularis gigantocellularis: Effect on the antinociception produced by microinjection of morphine and focal electrical stimulation in
the periaqueductal gray matter. Brain
Res 231:143-152, 1982
Nakahama H, Shima K, Aya K, et al:
Peripheral somatic activation and spontaneous firing patterns of neurons in
the periaqueductal gray of the cat. Neurosci Lett 25:43-46, 1981
Nakahama H, Shima K, Aya K, et al:
Antionociceptive action of morphine
Volume 6 5 / Number 3 , March 1 9 8 5
106.
107.
108.
109.
110.
111.
112.
and pentazocine on unit activity in the
nucleus centralis lateralis, nucleus ventralis lateralis and nearby structures of
the cat. Pain 10:47-56, 1981
Necker R, Hellon RF: Noxious thermal
input from the rat tail: Modulation by
descending inhibitory influences. Pain
4:231-242, 1978
Oleson TD, Kirkpatrick DB, Goodman
SJ: Elevation of pain threshold to tooth
shock by brain stimulation in primates.
Brain Res 194:79-95, 1980
Oleson TD, Twombly DA, Liebeskind
JC: Effects of pain-attenuating brain
stimulation and morphine on electrical
activity in the raphe nuclei of the awake
cat. Pain 4:211-230, 1978
Oliveras JL, Hosobuchi Y, Guilbaud G,
et al: Analgesic electrical stimulation of
the feline nucleus raphe magnus: Development of tolerance and its reversal
by 5-HTP. Brain Res 146:404-409,
1978
Olpe H-R: The cortical projection of the
dorsal raphe nucleus: Some electrophysiological and pharmacological
properties. Brain Res 216:61-71, 1981
Peschanski M, Guilbaud G, Gautron M:
Neuronal responses to cutaneous electrical and noxious mechanical stimuli in
the nucleus reticularis thalami of the
rat. Neurosci Lett 20:165-170, 1980
Pomeroy SL, Behbehani MM: Physiologic evidence for a projection from
periaqueductal gray to nucleus raphe
magnus in the rat. Brain Res 176:143-
147, 1979
113. Prieto GJ, Cannon JT, Liebeskind JC:
N. raphe magnus lesions disrupt stimulation-produced analgesia from ventral but not dorsal midbrain areas in the
rat. Brain Res 261:53-57, 1983
114. Proudfit HK: Reversible inactivation of
raphe magnus neurons: Effects on nociceptive threshold and morphine-induced analgesia. Brain Res 201:459-
464, 1980
115. Rhodes DL: Periventricular system lesions and stimulation-produced analgesia. Pain 7:51-63, 1979
116. Rhodes DL, Liebeskind JC: Analgesia
from rostral brain stem stimulation in
the rat. Brain Res 143:521-532,1978
117. Rivot JP, Chiang CY, Besson JM: Increase of serotonin metabolism within
the dorsal horn of the spinal cord during
nucleus raphe magnus stimulation, as
revealed by in vivo electrochemical detection. Brain Res 238:117-126, 1982
118. Rosenfeld JP, Holzman BS: Effects of
morphine on medial thalamic and medial bulboreticular aversive stimulation
thresholds. Brain Res 150:436-440,
1978
119. Rosenfeld JP, Stocco S: Differential effects of systemic versus intracranial injection of opiates on central, orofacial
and lower body nociception: Somatotypy in bulbar analgesia systems. Pain
9:307-318, 1980
120. Sagen J, Proudfit HK: Hypoalgesia induced by blockade of noradrenergic
projections to the raphe magnus: Reversal by blockade of noradrenergic
projections to the spinal cord. Brain
Res 223:391-396, 1981
121. Salt TE, Hill RG: Pharmacological differentiation between responses of rat
medullary dorsal horn neurons to noxious mechanical and noxious thermal
cutaneous stimuli. Brain Res 263:167171, 1983
122. Sanders KH, Klein CE, Mayer TE, et al:
Differential effects of noxious and nonnoxious input on neurones according
to location in ventral periaqueductal
grey or dorsal raphe nucleus. Brain Res
186:83-97, 1980
123. Satoh M, Akaike A, Takagi H: Excitation by morphine and enkephalin of single neurons of nucleus reticularis paragigantocellularis in the rat: A probable
mechanism of analgesic action of
opioids. Brain Res 169:406-410,1979
124. Segal M: Serotonergic innervation of
the locus coeruleus from the dorsal
raphe and its action on responses to
noxious stimuli. J Physiol (Lond)
286:401-415, 1979
125. Sessle BJ, Hu JW: Raphe-induced
suppression of the jaw-opening reflex
and single neurons in trigeminal subnucleus oralis, and influence of naloxone and subnucleus caudalis. Pain
10:19-36, 1981
126. Shah Y, Dostrovsky JO: Electrophysiological evidence for a projection of the
periaqueductal gray matter to nucleus
raphe magnus in cat and rat. Brain Res
193:534-538, 1980
127. Sinclair JG, Fox RE, Mokha SS, et al:
The effect of naloxone on the inhibition
of nociceptor driven neurones in the cat
spinal cord. Q J Exp Physiol 65:181188, 1980
128. Soja PJ, Sinclair JG: The response of
dorsal horn neurones of the cat to intraarterial bradykinin and noxious radiant
heat. Neurosci Lett 20:183-188,1980
129. Soper WY, Melzack R: Stimulation-produced analgesia: Evidence for somatotopic organization in the midbrain.
Brain Res 251:301-311, 1982
130. Strahlendorf HK, Strahlendorf JC,
Barnes CD: Endorphin-mediated inhibition of locus coeruleus neurons. Brain
Res 191:284-288, 1980
131. Strahlendorf JC, Strahlendorf HK,
Barnes CD: Inhibition of periaqueductal
gray neurons by the arcuate nucleus:
Partial mediation by an endorphin pathway. Exp Brain Res 46:462-466, 1982
132. Terman GW, Lewis JW, Liebeskind JC:
Opioid and non-opioid mechanisms of
stress analgesia: Lack of cross-tolerance between stressors. Brain Res
260:147-150, 1983
133. Toyooka H, Kitahata LM, Dohi S, et al:
Effects of morphine on the rexed lamina
VII spinal neuronal response to graded
noxious radiant heat stimulation. Exp
Neurol 62:146-158, 1978
134. Trevino DL: Integration of sensory input
in laminae I, II and III of the cat's spinal
cord. Fed Proc 37:2234-2236, 1978
135. Urea G, Nahin RL, Liebeskind JC: Effects of morphine on spontaneous multiple-unit activity: Possible relation to
mechanisms of analgesia and reward.
Exp Neurol 66:248-262, 1979
327
15. 136. Urca G, Liebeskind JC: Electrophysiological indices of opiate action in awake
and anesthetized rats. Brain Res
161:162-166, 1979
137. Vidal C, Jacob J: The effect of medial
hypothalamus lesions on pain control.
Brain Res 199:89-100, 1980
138. Wall PD, Devor M, inbal R, et al: Auto
tomy following peripheral nerve lesions:
Experimental anaesthesia dolorosa.
Pain 7:103-113, 1979
139. Wang RY, Aghajanian GK: Correlative
firing patterns of serotonergic neurons
in rat dorsal raphe nucleus. J Neurosci
2:11-16, 1982
140. Warren PH, Ison JR: Selective action
of morphine on reflex expression to
nociceptive stimulation in the rat: A
contribution to the assessment of analgesia. Pharmacol Biochem Behav
16:869-874, 1982
141. Watkins LR, Cobelli DA, Newsome HH,
et al: Footshock induced analgesia is
dependent neither on pituitary nor sympathetic activation. Brain Res 245:81 96, 1982
142. Watkins LR, Cobelli DA, Mayer DJ: Opiate vs non-opiate footshock induced
analgesia (FSIA) descending and intraspinal components. Brain Res 245:97106,1982
143. Watkins LR, Drugan R, Hyson RL, et
al: Opiate and non-opiate analgesia induced by inescapable tail-shock: Effects of dorsolateral funiculus lesions
and decerebration. Brain Res 291:325336, 1984
144. Watkins LR, Griffin G, Leichnetz GR, et
al: Identification and somatotopic organization of nuclei projecting via the
dorsolateral funiculus in rats: A retrograde tracing study using HRP slowrelease gels. Brain Res 223:237-255,
1981
145. Watkins LR, Griffin G, Leichnetz GR, et
al: The somatotopic organization of the
nucleus raphe magnus and surrounding brain stem structures as revealed
by HRP slow-release gels. Brain Res
181:1-15,1980
146. Watkins LR, Johannessen JN, Kinscheck IB, et al: The neurochemical
basis of footshock analgesia: The role
of spinal cord serotonin and norepinephrine. Brain Res 290:107-117,
1984
147. Watkins LR, Kinscheck IB, Mayer DJ:
The neural basis of footshock analgesia: The effect of periaqueductal gray
lesions and decerebration. Brain Res
276:317-324, 1983
148. Watkins LR, Mayer DJ: Involvement of
spinal opioid systems in footshock-induced analgesia: Antagonism by naloxone is possible only before induction
of analgesia. Brain Res 242:309-316,
1982
149. Watkins LR, Mayer DJ: Organization of
endogenous opiate and nonopiate pain
control systems. Science 216:11851192,1982
150. Watkins LR, Young EG, Kinscheck IB,
et al: The neural basis of footshock
analgesia: The role of specific ventral
medullary nuclei. Brain Res 276:305315, 1983
328
151. Weil-Fugazza J, Godefroy F, Coudert
D, et al: Morphine analgesia and newly
synthesized 5-hydroxytryptamine in the
dorsal and the ventral halves of the
spinal cord of the rat. Brain Res
214:440-444, 1981
152. Willis WD, Gerhart KD, Willcockson
WS, et al: Primate raphe- and reticulospinal neurons effects of stimulation in
periaqueductal gray or VPL thalamic
nucleus. J Neurophysiol 51:467-480,
1984
153. Willis WD, Kevetter GA: Spinothalamic
cells in the rat lumbar cord with collaterals to the medullary reticular formation. Brain Res 238:181-185, 1982
154. Willis WD, Kenshalo DR, Leonard RB,
et al: Facilitation of the responses of
primate spinothalamic cells to cold and
to tactile stimuli by noxious heating of
the skin. Pain 12:141-152, 1982
155. Wong CL, Bentley GA: The effect of
stress and adrenalectomy on morphine
analgesia and naloxone potency in
mice. Eur J Pharmacol 56:197-205,
1979
156. Woolf CJ, Wall PD: Chronic peripheral
nerve section diminishes the primary
afferent A-fibre mediated inhibition of
rat dorsal horn neurones. Brain Res
242:77-85, 1982
157. Yezierski RP, Gerhart KD, Schrock BJ,
et al: A further examination of effects
of cortical stimulation on primate spinothalamic tract cells. J Neurophysiol
49:424-441, 1983
158. Yokota T: Differential inhibitory effects
of volleys from dorsal raphe nucleus
upon spinal and spino-bulbo-spinal reflexes. Neurosci Lett 7:291-294, 1978
159. Young EG, Watkins LR, Mayer DJ:
Comparison of the effects of ventral
medullary lesions on systemic and microinjection morphine analgesia. Brain
Res 290:119-129, 1984
160. Zamir N, Shuber E: Altered pain perception in hypertensive humans. Brain
Res 201:471-474, 1980
161. Zamir N, Simantov R, Segal M: Pain
sensitivity and opioid activity in genetically and experimentally hypertensive
rats. Brain Res 184:299-310, 1980
162. Zieglgansberger W, Tulloch IF: The effects of methionine- and leucine-enkephalin on spinal neurones of the cat.
Brain Res 167:53-64, 1979
163. Zorman G, Hentall ID, Adams JE, et al:
Naloxone-reversible analgesia produced by microstimulation in the rat
medulla. Brain Res 219:137-148, 1981
PAIN: GENERAL CLINICALSURGICAL APPROACHES
1. Amodei N, Paxinos G: Unilateral knife
cuts produce ipsilateral suppression of
responsiveness to pain in the formalin
test. Brain Res 193:85-94, 1980
2. Aronoff GM, Evans WO, Enders PL: A
review of follow-up studies of multidisciplinary pain units. Pain 16:1-11, 1983
3. Badawy AA-B, Evans M, Punjani NF, et
al: Does naloxone always act as an
opiate antagonist? Life Sci 33:739-742,
1983
4. Carlen PL, Wall PD, Nadvorna H, et al:
Phantom limbs and related phenomena
in recent traumatic amputation. Neurology 28:211-217, 1978
5. Carstens E, Guinan MJ, MacKinnon JD:
Naloxone does not consistently affect
inhibition of spinal nociceptive transmission produced by medial diencephalic
stimulation in the cat. Neurosci Lett
42:71-76, 1983
6. Chayen MS, Rudick V, Borvine A: Pain
control with epidural injection of morphine. Anesthesiology 53:338-339,
1980
7. Cohen FL: Postsurgical pain relief: Patients' status and nurses' medication
choices. Pain 9:265-274, 1980
8. Croze S, Duclaux R: Thermal pain in
humans: Influence of the rate of stimulation. Brain Res 157:418-421, 1978
9. Devor M: Nerve pathophysiology and
mechanisms of pain in causalgia. J Auton
Nerv Syst 7:371-384, 1983
10. File SE: Naloxone reduces social and
exploratory activity in the rat. Psychopharmacology (Berlin) 71:41-44, 1980
11. Gracely RH, Dubner R: Pain assessment
in humans—a reply to Hall. Pain 11:109120, 1981
12. Holden C: Pain, dying, and the health
care system. Science 203:984-986,
1979
13. Jacquet YF: Different behavioral effects
following intracerebral, intracerebroventricular or intraperitoneal injections of
naloxone in the rat. Behav Brain Res
1:543-546, 1980
14. Kenton B, Coger R, Crue B, et al: Peripheral fiber correlates to noxious thermal stimulation in humans. Neurosci Lett
17:301-306, 1980
15. MacDonald AJR: Abnormally tender
muscle regions and associated painful
movements. Pain 8:197-205, 1980
16. Maruyama Y, Shimoji K, Shimizu H, et
al: Effects of morphine on human spinal
cord and peripheral nervous activities.
Pain 8:63-73, 1980
17. Nashold BS, Ostdahl RH: Dorsal root
entry zone lesions for pain relief. J Neurosurg 51:59-69, 1979
18. Sherman RA, Sherman CJ, Gall NG: A
survey of current phantom limb pain
treatment in the United States. Pain
8:85-99, 1980
19. Strassburg HM, Thoden U, Mundinger
F: Mesencephalic chronic electrodes in
pain patients. Appl Neurophysiol
42:284-293, 1979
20. Varni JW, Gilbert A, Dietrich SL: Behavioral medicine in pain and analgesia in
management for the hemophilic child
with factor VIII inhibitor. Pain 11:121126, 1981
21. Wahlstrom A, Terenius L: Factor in human CSF with apparent morphine-antagonistic properties. Acta Physiol Scand
110:427-429, 1980
22. Walker JM, Moises HC, Coy DH, et al:
Nonopiate effects of dynorphin and destyr-dynorphin. Science 218:1136-1138,
1982
23. Watson SJ, Khachaturian H, Akil H, et
al: Comparison of the distribution of dynorphin systems and enkephalin sysPHYSICAL THERAPY