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Varying Frequency and Intensity in TENS Application for
Acute and Chronic Pain
So possibly, the motor level may facilitate a different level of stimulation and hence the
possibility of utilizing both (1). Both high frequency and low frequency have been shown
to be effective in acute pain associated with injury and inflammation (2, 3). There
seems to be benefit in reducing motor neuron excitability (spasm reduction, muscle
reeducation by de-stimulation of over active muscle, retraining inhibited) and this is
better accomplished short term high frequency (4,5). Inflammation and pain may be
modulated differently at the different time courses of a condition, e.g. high frequency is
more effective in inflammation and pain associated with such (6).
In summary, there seems be benefits of both, however combining the motor/sensory
and high/low frequencies may be more beneficial in the chronic cases, especially due to
comfort and wear ability. Pain in general influences motor responses and chronic pain
further disrupts both sensory and motor responses. Sensory stimulation response has
also been used in prediction outcomes for motor performance.

1. Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous
electrical nerve stimulation-Induced antihyperalgesia.J Pain. 2005 Oct;6(10):673-80.
Radhakrishnan R, Sluka KA.
Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research
Program, Neuroscience Graduate Program, University of Iowa, Iowa City, Iowa 52242,
USA.
Abstract
In this study we investigated the involvement of cutaneous versus knee joint afferents in
the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by
differentially blocking primary afferents with local anesthetics. Hyperalgesia was
induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by
measuring paw withdrawal latency to heat before and 4 hours after injection. Skin
surrounding the inflamed knee joint was anesthetized using an anesthetic cream
(EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the
anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed
knee joint, and low or high frequency TENS was applied. Control experiments were done
using vehicles. In control and EMLA groups, both low and high frequency TENS
completely reversed hyperalgesia. However, injection of lidocaine into the knee joint
prevented antihyperalgesia produced by both low and high frequency TENS. Recordings
of cord dorsum potentials showed that both low and high frequency TENS at sensory
intensity activates only large diameter afferent fibers. Increasing intensity to twice the
motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream
to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both
high and low frequency TENS, confirming a loss of large diameter primary afferent input
after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous
afferents, prevents the antihyperalgesia effects of TENS. We conclude that large
diameter primary afferent fibers from deep tissue are required and that activation of
cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. PERSPECTIVE:
Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used
for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous
afferent activation. In this study by differentially blocking cutaneous and deep tissue
primary afferents, we show that the activation of large diameter primary afferents from
deep somatic tissues, and not cutaneous afferents, are pivotal in causing TENS
analgesia.
PMID: 16202960 [PubMed - indexed for MEDLINE]
1.The effect of varying frequency and intensity of transcutaneous electrical nerve
stimulation on secondary mechanical hyperalgesia in an animal model of
inflammation.J Pain. 2001 Apr;2(2):128-33.
King EW, Sluka KA.
Graduate Program in Physical Therapy and Rehabilitation, Neuroscience Graduate
Program, College of Medicine, University of Iowa, Iowa City, 52242, USA.
Abstract
For years, transcutaneous electrical nerve stimulation (TENS) has been used clinically for
the treatment of many types of pain. Although there have been many studies conducted
on the efficacy of TENS in the clinical setting, the results are conflicting. The purpose of
our investigation was to determine the effect of varying frequency and intensity of TENS
on secondary mechanical hyperalgesia induced by acute joint inflammation. Male
Sprague-Dawley rats were injected with a mixture of 3% carrageenan and 3% kaolin
(100 microL in 0.9% sterile saline) into the joint cavity of one knee. The response
threshold to mechanical stimuli was determined before inflammation of the knee joint;
4 hours after inflammation; immediately after the administration of TENS
(approximately 5 hours after inflammation); and at 8, 12, and 24 hours after
inflammation. TENS was applied to the inflamed knee joint at either high (100 Hz) or low
(4 Hz) frequency and at either sensory or motor intensity. Sensory intensity was just
below the threshold for motor contraction, and motor intensity was 2 x threshold for
motor contraction. Either low- or high-frequency TENS is equally successful in reducing
secondary mechanical hyperalgesia. Similarly, either sensory- or motor-intensity TENS
equally reduces secondary mechanical hyperalgesia. Thus, selection of TENS should be
based on patient comfort and symptoms for relief of secondary mechanical
hyperalgesia.
2.Effect of varying frequency, intensity, and pulse duration of transcutaneous
electrical nerve stimulation on primary hyperalgesia in inflamed rats.
Gopalkrishnan P, Sluka KA.Arch Phys Med Rehabil. 2000 Jul;81(7):984-90.
Physical Therapy Graduate Program, College of Medicine, University of Iowa, Iowa City
52242, USA.
Abstract
OBJECTIVES: To examine the effect of varying frequency, intensity, and pulse duration of
transcutaneous electrical nerve stimulation (TENS) on primary hyperalgesia (increased
response to a noxious stimuli) to heat and mechanical stimuli induced by carrageenan
paw inflammation in rats.
DESIGN: Inflammation was induced by injection of 3% carrageenan into the hindpaw.
Two frequencies (high, 100 Hz; low, 4 Hz), 2 intensities (high, motor; low, sensory), and
2 pulse durations (100 microsec, 250 microsec) were applied for 20 minutes to the
inflamed paw. The paw withdrawal latency (PWL) to radiant heat, threshold to
mechanical stimuli, and spontaneous pain-related behaviors were measured before and
4 hours after induction of inflammation, after TENS, and at 8, 12, and 24 hours after
inflammation. A 3-factor (frequency, intensity, pulse duration) repeated-measures
(time) design was used to analyze the changes in PWL. Mechanical threshold and
spontaneous pain-related behaviors were compared for frequency, intensity, and pulse
duration with a Kruskal-Wallis analysis of variance.
RESULTS: For changes in PWL to heat, there was an effect for time (p = .0001) and
frequency (p =.0001), but not for intensity (p = .45) or pulse duration (p = .21). For
changes in mechanical threshold, there was also an effect for frequency (p = .007), but
not for intensity (p = .055) or pulse duration (p = .058), after treatment with TENS. Highfrequency TENS significantly reduced the primary hyperalgesia to heat and mechanical
stimuli when compared with controls receiving no TENS or treatment with lowfrequency TENS. High-frequency motor TENS also reduced spontaneous pain-related
behaviors for 1 day after treatment.
CONCLUSION: High-frequency TENS reduces primary hyperalgesia to heat and
mechanical stimuli for up to 1 day after treatment. In contrast, low-frequency TENS is
ineffective in reducing primary hyperalgesia. Varying intensity or pulse duration had no
effect on the degree of antihyperalgesia produced by high-frequency TENS.
3.Short-term high-frequency transcutaneous electrical nerve stimulation decreases
human motor cortex excitability
Neuroscience Letters
Volume 355, Issues 1-2, 23 January 2004, Pages 85-88
Tatsuya Mima, , a, Tatsuhide Ogaa, John Rothwella, b, Takeshi Satowa, c, Jun-ichi
Yamamotoa, c, Keiichiro Tomad, Hidenao Fukuyamaa, Hiroshi Shibasakia, e and Takashi
Nagaminea
Abstract
Several pervious studies have shown that periods of changed sensory input can have
after effects on the excitability of the corticospinal system. Here we test whether the
parameters of peripheral stimulation conventionally used to treat pain with
transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects
on the motor system. We measured the amplitude of motor evoked potentials (MEPs)
elicited by the focal transcranial magnetic stimulation in the right abductor pollicis
brevis and first dorsal interosseous muscles before and after 30 min TENS over the right
thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds
at the same site. TENS transiently reduced MEPs and increased sensory thresholds. This
suggests that short-term TENS might have an inhibitory effect on both the sensory and
motor systems.
Author Keywords: Transcutaenous electrical nerve stimulation; Transcranial magnetic
stimulation; Sensorimotor cortex; Plasticity; Sensory threshold; Motor excitability
Article Outline
• Acknowledgements
• References

4.Long-lasting modulation of human motor cortex following prolonged
transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of
reciprocal inhibition and facilitation.Exp Brain Res. 2005 Mar;161(4):457-64. Epub 2004
Nov 16.
Tinazzi M, Zarattini S, Valeriani M, Romito S, Farina S, Moretto G, Smania N, Fiaschi A,
Abbruzzese G.
Abstract
Several lines of evidence indicate that motor cortex excitability can be modulated by
manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in
humans mainly dealt with the effects of prolonged low-frequency peripheral nerve
stimulation on motor cortical excitability, despite its being known from animal studies
that high-frequency stimulation can also result in changes of the cortical excitability. To
investigate the possible effects of high-frequency peripheral stimulation on motor
cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial
magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis
(FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects,
before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration
applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced
from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No
effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and
spinal cord excitability (H waves) did not change throughout the experiment. Electrical
stimulation of the lateral antebrachial cutaneous nerve has no significant effect on
motor cortex excitability. These findings suggest that TENS of forearm muscles can
induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal
excitability of forearm flexor and extensor muscles lasting several minutes. These
changes probably may occur at cortical site and seem to be mainly dependent on
stimulation of muscle afferents. These findings might eventually lead to practical
applications in rehabilitation, especially in those syndromes in which the excitatory and
inhibitory balance between agonist and antagonist is severely impaired, such as
spasticity and dystonia.
PMID: 15551083 [PubMed - indexed for MEDLINE]

5.Low frequency TENS is less effective than high frequency TENS at reducing
inflammation-induced hyperalgesia in morphine-tolerant rats.Eur J Pain.
2000;4(2):185-93.
Sluka KA, Judge MA, McColley MM, Reveiz PM, Taylor BM.
Physical Therapy, The University of Iowa, Iowa City 52241, USA. kathleensluka@uiowa.edu
Abstract
Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly
used for relief of pain. Extensive research has been done on the effectiveness of each of
these two methods for pain relief when given independently. However, very little
literature exists examining the effectiveness of their combined use. Systemically
administered morphine activates mu opioid receptors and when administered for
prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency
TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS
would be less effective in morphine-tolerant subjects. The current study investigated
the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in
inflamed rats that were morphine-tolerant. Morphine tolerance was induced by
subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation
was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary
heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat
(1) before pellet implantation (either morphine or placebo), (2) after pellet implantation
and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz)
and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia
in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant
animals with knee joint inflammation was unaffected by low frequency TENS but fully
reversed by high frequency TENS. These results suggest that patients who are tolerant
to morphine may respond better to high frequency TENS than to low frequency TENS.
Copyright 2000 European Federation of Chapters of the International Association for the
Study of Pain.

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Varying TENS Frequencies and Intensities for Acute and Chronic Pain Management

  • 1. Varying Frequency and Intensity in TENS Application for Acute and Chronic Pain So possibly, the motor level may facilitate a different level of stimulation and hence the possibility of utilizing both (1). Both high frequency and low frequency have been shown to be effective in acute pain associated with injury and inflammation (2, 3). There seems to be benefit in reducing motor neuron excitability (spasm reduction, muscle reeducation by de-stimulation of over active muscle, retraining inhibited) and this is better accomplished short term high frequency (4,5). Inflammation and pain may be modulated differently at the different time courses of a condition, e.g. high frequency is more effective in inflammation and pain associated with such (6). In summary, there seems be benefits of both, however combining the motor/sensory and high/low frequencies may be more beneficial in the chronic cases, especially due to comfort and wear ability. Pain in general influences motor responses and chronic pain further disrupts both sensory and motor responses. Sensory stimulation response has also been used in prediction outcomes for motor performance. 1. Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-Induced antihyperalgesia.J Pain. 2005 Oct;6(10):673-80. Radhakrishnan R, Sluka KA. Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research Program, Neuroscience Graduate Program, University of Iowa, Iowa City, Iowa 52242, USA. Abstract In this study we investigated the involvement of cutaneous versus knee joint afferents in the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by differentially blocking primary afferents with local anesthetics. Hyperalgesia was induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency to heat before and 4 hours after injection. Skin surrounding the inflamed knee joint was anesthetized using an anesthetic cream (EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed knee joint, and low or high frequency TENS was applied. Control experiments were done using vehicles. In control and EMLA groups, both low and high frequency TENS completely reversed hyperalgesia. However, injection of lidocaine into the knee joint prevented antihyperalgesia produced by both low and high frequency TENS. Recordings of cord dorsum potentials showed that both low and high frequency TENS at sensory intensity activates only large diameter afferent fibers. Increasing intensity to twice the
  • 2. motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both high and low frequency TENS, confirming a loss of large diameter primary afferent input after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous afferents, prevents the antihyperalgesia effects of TENS. We conclude that large diameter primary afferent fibers from deep tissue are required and that activation of cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. PERSPECTIVE: Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous afferent activation. In this study by differentially blocking cutaneous and deep tissue primary afferents, we show that the activation of large diameter primary afferents from deep somatic tissues, and not cutaneous afferents, are pivotal in causing TENS analgesia. PMID: 16202960 [PubMed - indexed for MEDLINE] 1.The effect of varying frequency and intensity of transcutaneous electrical nerve stimulation on secondary mechanical hyperalgesia in an animal model of inflammation.J Pain. 2001 Apr;2(2):128-33. King EW, Sluka KA. Graduate Program in Physical Therapy and Rehabilitation, Neuroscience Graduate Program, College of Medicine, University of Iowa, Iowa City, 52242, USA. Abstract For years, transcutaneous electrical nerve stimulation (TENS) has been used clinically for the treatment of many types of pain. Although there have been many studies conducted on the efficacy of TENS in the clinical setting, the results are conflicting. The purpose of our investigation was to determine the effect of varying frequency and intensity of TENS on secondary mechanical hyperalgesia induced by acute joint inflammation. Male Sprague-Dawley rats were injected with a mixture of 3% carrageenan and 3% kaolin (100 microL in 0.9% sterile saline) into the joint cavity of one knee. The response threshold to mechanical stimuli was determined before inflammation of the knee joint; 4 hours after inflammation; immediately after the administration of TENS (approximately 5 hours after inflammation); and at 8, 12, and 24 hours after inflammation. TENS was applied to the inflamed knee joint at either high (100 Hz) or low (4 Hz) frequency and at either sensory or motor intensity. Sensory intensity was just below the threshold for motor contraction, and motor intensity was 2 x threshold for motor contraction. Either low- or high-frequency TENS is equally successful in reducing secondary mechanical hyperalgesia. Similarly, either sensory- or motor-intensity TENS equally reduces secondary mechanical hyperalgesia. Thus, selection of TENS should be based on patient comfort and symptoms for relief of secondary mechanical hyperalgesia.
  • 3. 2.Effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation on primary hyperalgesia in inflamed rats. Gopalkrishnan P, Sluka KA.Arch Phys Med Rehabil. 2000 Jul;81(7):984-90. Physical Therapy Graduate Program, College of Medicine, University of Iowa, Iowa City 52242, USA. Abstract OBJECTIVES: To examine the effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation (TENS) on primary hyperalgesia (increased response to a noxious stimuli) to heat and mechanical stimuli induced by carrageenan paw inflammation in rats. DESIGN: Inflammation was induced by injection of 3% carrageenan into the hindpaw. Two frequencies (high, 100 Hz; low, 4 Hz), 2 intensities (high, motor; low, sensory), and 2 pulse durations (100 microsec, 250 microsec) were applied for 20 minutes to the inflamed paw. The paw withdrawal latency (PWL) to radiant heat, threshold to mechanical stimuli, and spontaneous pain-related behaviors were measured before and 4 hours after induction of inflammation, after TENS, and at 8, 12, and 24 hours after inflammation. A 3-factor (frequency, intensity, pulse duration) repeated-measures (time) design was used to analyze the changes in PWL. Mechanical threshold and spontaneous pain-related behaviors were compared for frequency, intensity, and pulse duration with a Kruskal-Wallis analysis of variance. RESULTS: For changes in PWL to heat, there was an effect for time (p = .0001) and frequency (p =.0001), but not for intensity (p = .45) or pulse duration (p = .21). For changes in mechanical threshold, there was also an effect for frequency (p = .007), but not for intensity (p = .055) or pulse duration (p = .058), after treatment with TENS. Highfrequency TENS significantly reduced the primary hyperalgesia to heat and mechanical stimuli when compared with controls receiving no TENS or treatment with lowfrequency TENS. High-frequency motor TENS also reduced spontaneous pain-related behaviors for 1 day after treatment. CONCLUSION: High-frequency TENS reduces primary hyperalgesia to heat and mechanical stimuli for up to 1 day after treatment. In contrast, low-frequency TENS is ineffective in reducing primary hyperalgesia. Varying intensity or pulse duration had no effect on the degree of antihyperalgesia produced by high-frequency TENS.
  • 4. 3.Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability Neuroscience Letters Volume 355, Issues 1-2, 23 January 2004, Pages 85-88 Tatsuya Mima, , a, Tatsuhide Ogaa, John Rothwella, b, Takeshi Satowa, c, Jun-ichi Yamamotoa, c, Keiichiro Tomad, Hidenao Fukuyamaa, Hiroshi Shibasakia, e and Takashi Nagaminea Abstract Several pervious studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds at the same site. TENS transiently reduced MEPs and increased sensory thresholds. This suggests that short-term TENS might have an inhibitory effect on both the sensory and motor systems. Author Keywords: Transcutaenous electrical nerve stimulation; Transcranial magnetic stimulation; Sensorimotor cortex; Plasticity; Sensory threshold; Motor excitability Article Outline • Acknowledgements • References 4.Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation.Exp Brain Res. 2005 Mar;161(4):457-64. Epub 2004 Nov 16. Tinazzi M, Zarattini S, Valeriani M, Romito S, Farina S, Moretto G, Smania N, Fiaschi A, Abbruzzese G. Abstract Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve
  • 5. stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia. PMID: 15551083 [PubMed - indexed for MEDLINE] 5.Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats.Eur J Pain. 2000;4(2):185-93. Sluka KA, Judge MA, McColley MM, Reveiz PM, Taylor BM. Physical Therapy, The University of Iowa, Iowa City 52241, USA. kathleensluka@uiowa.edu Abstract Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly used for relief of pain. Extensive research has been done on the effectiveness of each of these two methods for pain relief when given independently. However, very little literature exists examining the effectiveness of their combined use. Systemically administered morphine activates mu opioid receptors and when administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS would be less effective in morphine-tolerant subjects. The current study investigated the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation
  • 6. was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat (1) before pellet implantation (either morphine or placebo), (2) after pellet implantation and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant animals with knee joint inflammation was unaffected by low frequency TENS but fully reversed by high frequency TENS. These results suggest that patients who are tolerant to morphine may respond better to high frequency TENS than to low frequency TENS. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.