1. CHRONIC PAIN IN
PSYCHIATRIC PRACTICE
DEFINITION OF ACUTE AND CHRONIC PAIN, NOCICEPTIVE AND
NEUROPATHIC PAIN, PERIPHERAL AND CENTRAL SENSITIZATION, PAIN
AND MOOD, PHARMACOLOGY OF PAIN, CHRONIC PAIN SYNDROMES
ADONIS SFERA, MD

2. RIVER OF PAIN
Acheron was known as the river of pain, and was one of the five rivers
of the Greek underworld.

3. THE HISTORY OF MEDICINE IS THE
HISTORY OF PAIN
• Asclepius, the god of medicine attending to a
patient in pain

4. MORPHEUS AND HIS ELIXIR

5. TWO PARALLEL HISTORIES: ACUTE
AND CHRONIC PAIN
Acute Pain Chronic Pain
Physiological: protective (survival Pathological: non-protective (no
benefit) survival benefit)
Causes external: obvious Causes internal: obscure
Tissue damage: resolution within CNS changes: may not resolve
days/weeks
Attended by physicians (illness) Attended by clergy (suffering)
Symptom of illness Existential: a social phenomenon
The demon is outside The demon is within

6. CHRONIC PAIN: A WAY OF LIFE
• Headaches, backaches, pain in amputated limbs,
causalgias and neuralgias have always existed, but
the sufferers were not always considered “ill”.

7. “A WAY OF LIFE” IN OUR SOCIETY
• Destitution, Poverty, Homelessness affect health, yet
are not being addressed by medical science (a
way of life).

8. MEDICALIZATION OF CHRONIC PAIN
• In March of 1899 Felix Hoffman discovered Aspirin.
• Aspirin was more than a drug – it changed the way of thinking
about chronic pain.
• Pain and suffering became medicalized (medical model
applied).

9. A CULTURE OF PAIN AND PAINKILLERS
• In 2005 more than 10 million Americans were abusing prescription medications –
which is more than the combined number of people abusing cocaine, heroin,
hallucinogens and inhalants.
• Prescription painkiller overdoses killed nearly 15,000 people in the US in 2008 (three
times the 4,000 people killed by these drugs in1999).
Scott M. Fishman, MD; Responsible opioid prescribing a physician’s guide; Waterford Life Sciences, 2007

10. A “PERFECT STORM” OF CONTROVERSY
*War on pain
*War on drugs
• Physicians are being
enlisted on both fronts:
-combating pain
-reducing the risk of diversion, abuse and addiction.

11. PHARMACOVIGILENCE
• The science of detecting, understanding and
preventing adverse effects or any other drug
related problem.

13. PAIN: DEFINITION
• “An unpleasant sensory and emotional experience
associated with actual or potential tissue damage
or described in terms of such damage” (International
Association for the Study of Pain (IASP).

14. PAIN - A LEARNED EXPERIENCE
• Each individual “learns” pain through experiences related to injury in
early life.
To hear about pain is to have doubt; to experience
pain is to have certainty.
(Elaine Scarry: The Body in Pain)

15. PAIN THAT IS PRONE TO BECOME
CHRONIC
• Type: post-op, post trauma, post-herpes
• Neuropathic component: nerve injury
• Disability and compensation
• Inadequate analgesia
• Prolonged pain before surgery
• Repeated surgeries
• Radiation or chemotherapy
• Psychiatric vulnerabilities

16. CLASSIFICATION OF CHRONIC PAIN
Perpheral Neuropathic Central
(nociceptive) (non-nociceptive)
Inflammation or Damage or Central
mechanical entrapment of
disturbance in
damage peripheral nerves
pain processing
Classic examples Classic examples
-osteoarthritis -diabetic peripheral Classic examples
-rheumatoid arthritis neuropathic pain -fibromyalgia
-post-herpetic -IBS
neuralgia -headaches
-LBP
-TMJ disorder
-Chronic pelvic
pain

17. ALLODYNIA AND HYPERALGESIA
Allodinia = Pain evoked by
innocuous stimuli.
Hyperalgesia =
exaggerated pain
produced by mildly painful
stimuli.

18. NOCICEPTION (THE AFFERENTS)
-A beta fibers respond only to non-noxious stimuli
-A delta and C fibers respond to noxious mechanical, heat, and
chemical stimuli.
Stephen M. Stahl;Stahl’s Essential Psychopharmacology; Third Edition;Cambridge University Press 2008

19. NOCICEPTION AND NEUROPATHY
1. Sensory Pathway =information
about the location and intensity of
the painful stimulus (spinothalamic
tract).
2. Emotional Pathway =affective
component of the pain experience
(spinobulbar tract).
Combined data from these
pathways = human subjective
experience of pain.

20. INSULAR CORTEX – WHERE PAIN
BECOMES SUFFERING

21. VON ECONOMO NEURONS (VEN):
INSULA AND ACC

22. THE PHYSIOLOGY OF INSULAR CORTEX
The insulae are believed to be involved in:
• emotion
• pain
• empathy
• perception,
• self-awareness,
• cognitive functioning,
• interpersonal experience.

23. EMPATHY IS PAIN … SORT OF
VEN in Insula and Anterior Cingulate Cortex (ACC) are
activated when subjects evaluate painful stimuli and when
empathizing with others who experience physical pain.
The Neural Basis of Empathy;Annual Review of Neuroscience,Vol. 35: 1-23 (Volume publication date July 2012);DOI: 10.1146/annurev-
neuro-062111-150536

24. VON ECONOMO NEURON DISCOVERED IN
THE INSULA OF MACAQUE MONKEYS
• Published on June 4, 2012: A scientist from the Max Planck Institute
discovered that von Economo neuron (VEN) is also found in the insula
of macaque monkeys

25. PERIPHERAL SENSITIZATION (PRIMARY
HYPERALGESIA)
SENSITIZING SOUP
• Hydrogen ions
• Noradrenaline
• Bradykinin
• Histamine
• Potassium ions
• Prostaglandins
• Purines
• Cytokines
• Serotonin
• Nerve growth factor
• neuropeptides

26. PERIPHERAL SENSITIZATION LEADS TO
CENTRAL SENSITIZATION

27. CENTRAL SENSITIZATION (SECONDARY
HYPERALGESIA)

28. PAIN BEGETS MORE PAIN (OVERACTIVE
ASCENDING PATHWAYS)
Long term potentiation
(LTP) is perpetuated by
pain and leads to
strengthened
synapses.
These stronger
synapses are able to:
recruit subliminal
inputs.

29. CAUSES OF SENSITIZATION?
When a nerve is severed,
the distal portion
degenerates and dies.
The proximal portion sprouts
trying to reach the previous
target tissue.
The sprouts lack guidance
and form tangeled
neuromas.
Neuromas generate
ectopic activity and
heightened sensitivity to
mechanical, thermal and
chemical stimuli.
Stephen M. Stahl;Stahl’s Essential
Psychopharmacology; Third
Edition;Cambridge University Press 2008

30. EPHAPTIC CROSS-TALK
Disruption to myelination
may also allow cross-talk
between
neurons(ephaptic cross-
talk).
The electrical activity in
an A beta fiber neuroma
can electrically stimulate
activity in a C fiber.
Repetitive firing of one
neuron can stimulate
activity in the
neighboring
neurons(hyperalgesia
and allodynia).
Stephen M. Stahl;Stahl’s Essential
Psychopharmacology; Third
Edition;Cambridge University Press
2008

31. FUNCTIONAL SOMATIC SYNDROMES
(FSS)
• Fibromyalgia
• Irritable bowel syndrome
• Chronic Fatigue Syndrom
• Temporomandibular Joint Disorder
• Interstitial cystitis
Patients with one FSS often suffer from one or more
other FSS as well as psychiatric comorbidity.

32. THE COMPLEX RELATIONSHIP
BETWEEN PAIN AND DEPRESSION
• The overlap between pain and depression ranges from 30% - 60%
• Depression may lower pain threshold (depressed people fell more pain)
• Pain may precipitate depression
• Patients with chronic pain are at higher risk of developing depression
• Pain and depression may be considered integrated.
Gallagher RM, Verma S. Semin; Clin Neuropsychiatry 1999; 4 :203-220;Von Korff M, Simon G; Br J Psychiatry.1996;168 (sup 30):101-103

33. PAIN PATIENTS IN PSYCHIATRIC
PRACTICE
Psychiatrist: Somatization d/o
Rheumatologist: fibromyalgia
Neurologist: chronic fatigue
syndrome/myalgic encephalomyelitis
Patient: “multiple chemical
sensitivities”

34. WAR ON PAIN (FRONTS)

35. SNRI DRUGS APPROVED FOR CHRONIC
PAIN
Duloxetine Milnacipran
60 mg once daily; higher doses increase SEs 30-200 mg/day in 2 doses
without increasing efficacy in pain disorders
Approved for multiple neuropathic pain Approved for fibromyalgia
disorders
SEs include nausea, dry mouth; can cause SEs: nausea, constipation, sweating, urologic
urinary retention, rare activation of suicidality, complaints, urinary hesitancy, dose-dependent
increase in blood pressure; can cause rare activation
rare hepatotoxicity
of suicidality
Metabolized by CYP 450 2D6 Few known adverse pharmacokinetic drug
interactions
Not for use with Thioridazine, MAOIs, or Not for use with MAOIs, or patients with uncontrolled
patients with uncontrolled narrow angle narrow angle glaucoma or hepatic impairment
glaucoma or hepatic impairment

36. OTHER SNRI DRUGS
Venlafaxine Desvenlafaxine
75-225 mg once daily 50 mg once daily
Clinical efficacy in reducing chronic pain Clinical efficacy in reducing chronic pain
SEs include headaches, insomnia, nausea, SEs include insomnia, nausea, constipation,
sweating, dose dependent increase in BP, rare sweating, increase in BP, rare activation of
activation of suicidality suicidality.
Use with caution in patients with cardiac Use with caution in patients with cardiac
impairment impairment
Not for use with MAOIs or in patients with Not for use with MAOIs or in patients with
uncontrolled narrow-angle glaucoma uncontrolled narrow-angle glaucoma

37. ALPHA 2 DELTA LIGANDS
Pregabalin Gabapentin
150-600 mg/day in 2-3 doses 900-1800 mg/day in 3 doses
Approved in multiple neuropathic Approved in postherpetic
pain disorders neuralgia
Most common SEs: sedation, Most common SEs: sedation,
dizziness dizziness, fatigue, ataxia,
nystagmus, tremor
Enhances slow-wave sleep Enhances slow-wave sleep
Renally excreted Renally excreted

38. ANTICONVULSANTS FOR CHRONIC
PAIN
Carbamazepine Oxcarbazepine Topiramate Lamotrigine Zonisamide
1200 mg/day; 1200-1400 50-300 mgday 100-300 mg/day 100-600 mg/day
start slow mg/day; start
slow
Approved for Adjunct for FDA approved Clinical efficacy Some clinical
trigeminal neuropathic for migraine in neuropathic efficacy in
neuralgia; may pain prophylaxis pain neuropathic
have efficacy in pain and
other migraines
neuropathic
pain disorders
Induces P450 Less Induction of May have Efficacy can
enzymes, may P450 enzymes efficacy in other wane after
lower the levels neuropathic several weeks of
of other drugs pain disorders. use

39. TRICYCLICS FOR CHRONIC PAIN
Amytriptiline Cyclobenzaprine
25-50 mg once daily 15 mg/day in 3 doses
Used for multiple pain disorders 15-30 mg/day in one dose (ER)
SEs include sedation, weight gain, Muscle relaxant
anticholinergic effects, dizziness, hypotension
Metabolized to nortriptyline by CYP 450 1A2 Not recommended for long term use
Significant drug-drug interactions SEs: sedation, dry mouth, fatigue headache
Use with caution in patients with renal or Use with caution in patients with urinary
hepatic impairment retention, angle-closure glaucoma, hepatic
impairment
Can have cardiovascular effects Can have cardiovascular effects
Multiple contraindications Do not use with MAOIs

40. ON THE OPIOID BORDER:
PROPOXYPHENE AND TRAMADOL

41. OTHER PAIN AGENTS
NSAIDs Acetaminophen Baclophen
Better for acute pain Less effect on bleeding Muscle relaxant and
or for chronic and renal function antispastic
inflammatory pain compared to NSAIDs
Warning for GI Can cause Used for trigeminal
bleeding with SSRIs hepatotoxicity at high neuralgia and some
doses other neuropathic pain
conditions
Combination with Many psychotropics Use with caution in
lithium may cause are metabolized by patients with renal
lithium toxicity the same liver enzymes impairment

42. OPIOIDS
• Effective for osteoarthritis, rheumatoid arthritis,
musculoskeletal pain, postherpetic neuralgia, phantom
limb pain, diabetic neuropathy, and chronic low back
pain.
• No studies of effectiveness beyond 8 weeks
• Not effective for fibromyalgia
• Risks (dependence, tolerance, pain worsening, reduced
effects of SSRIs)
Ballantyne JC, Shin NS; Clin J Pain 2008;24:469-78; Clauw. Am J Med 2009;(Suppl 12):S 3-13

43. OPIOIDS FOR CHRONIC PAIN: THE TWO
FACES OF JANUS
• Opioids may elicit paradoxical “pain” in both
animals and humans.
• In humans hyperalgesia is noted in areas of the
body different from the site of the original pain
complaint.
• Methadone maintenance patients are hyperalgesic.
• The mechanisms of opioid induced hyperalgesia are unknown
Frank Porreca, PHD, University of Arizona, Tucson, Arizona

44. NONPHARMACOLOGICAL
TREATMENTS FOR CHRONIC PAIN
• Cognitive behavioral therapy
-May work best if targeted to a specific outcome
-Adherence may be an issue
• Hypnosis, relaxation, guided imagery
-May reduce pain, distress
• Education
-Should be combined with other treatment approaches
-Education groups can be useful, but adherence may
be low
• Aerobic exercise

45. EVIDENCE BASED TREATMENT OF CHRONIC
PAIN SYNDROMES WITH HIGH PSYCHIATRIC
CO-MORBIDITY
1. Neuropathic Pain
2. Fibromyalgia
3. Chronic Back Pain
4. Osteoarthritis

46. NEUROPATHIC PAIN
• Diabetic neuropathy - 16% of persons with diabetes.
• Postherpetic neuralgia - up to 25% develop
neuropathic pain following an episode of shingles.
• Spinal stenosis – 3% develop neuropathic pain
• Lumbar disc herniation - 4% develop neuropathic
low back pain

47. FIRST LINE DRUGS FOR NEUROPATHIC
PAIN
• Gabapentin 900-3600 mg/day (Post-herpetic neuralgia)
• Pregabalin 75-600 mg/day (Diabetic Neuropathy, Post-
herpetic neuralgia)
• Duloxetine 60 mg daily (Diabetic neuropathy)
• Topical Agents: Lidoderm up to 3 patches/day (Post-herpetic
neuralgia)
Schatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009

48. DIAGNOSTIC CRITERIA FOR
FIBROMYALGIA
American College of Rheumatology:
1. Generalized pain that is both widespread (on both the
right and the left side of the body, upper and lower
halves, and axial as well as proximal arms and legs)
and chronic (lasting more than 3 months).
2. Multiple tender points on physical examination
(located in the front and back of the neck, upper chest
and back areas, iliosacral and posterior gluteal areas,
elbows and knees).
Schatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009

49. FIBROMYALGIA AND ACCELERATED
BRAIN GRAY MATTER LOSS
Less gray matter density in fibromyalgia
patients vs. controls :
-left parahippocampal gyrus (PHG),
-left and right mid/posterior cingulate gyrus
(CG)
-left insular cortex (IC), and
-medial frontal cortex
Anil Kuchinand, P.Schweinhardt, DA Seminowitz et al.; Accelerated brain Gray Mattewr
Tissue Loss in Fibromyalgia Patients: Premature Aging of the Brain, Society of Neuroscience
2007

50. FIBROMYALGIA - PHARMACOLOGIC AND NON-
PHARMACOLOGIC TREATMENTS
First line:
• SNRIs (Duloxetine, Milnacipran)
• Alpha2 Delta ligands (Pregabalin, Gabapentin)
• Aerobic Exercise
• CBT
• Education
Second line:
• TCAs
• Cyclobenzaprine (chemical structure related to TCAs)
• Tramadol
Schatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009

51. LOW BACK PAIN
• The most commonly prescribed medications for low
back pain are:
• NSAIDs,
• Muscle relaxants,
• Opioid analgesics.
• Benzodiazepines, systemic corticosteroids,
antidepressants and anticonvulsants are also prescribed.
• Schatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009

52. LOW BACK PAIN GENE?
A UK study, published in the Annals of Rheumatic Diseases (Sep. 24,
2012):
PARK2 gene was linked to age-related degeneration of the intervertebral
discs in the spine, a common cause of lower back pain.

53. LIFT WITH YOUR KNEES NOT YOUR
BACK

54. OSTEOARTHRITIS
• Osteophyte formation
• Focus of treatment: reduction of pain, preservation of function.
• Acetaminophen
• NSAID
• Aerobic exercise
• Opioids
• Not enough evidence for chondroitin, glucosamine and intra-articular hyaluronic
acid.
• Antidepressants not studied for pain in osteoarthritis, but Katon 2007 looked at the
co-morbidity of osteoarthritis with depression (antidepressants helpful) .
Schatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009

55. THANK YOU – LET’S STOP HERE