Pain and its treatment in psychiatric practice (2) (1)
CHRONIC PAIN IN PSYCHIATRIC PRACTICE DEFINITION OF ACUTE AND CHRONIC PAIN, NOCICEPTIVE ANDNEUROPATHIC PAIN, PERIPHERAL AND CENTRAL SENSITIZATION, PAIN AND MOOD, PHARMACOLOGY OF PAIN, CHRONIC PAIN SYNDROMES ADONIS SFERA, MD
RIVER OF PAINAcheron was known as the river of pain, and was one of the five riversof the Greek underworld.
THE HISTORY OF MEDICINE IS THE HISTORY OF PAIN• Asclepius, the god of medicine attending to a patient in pain
TWO PARALLEL HISTORIES: ACUTE AND CHRONIC PAINAcute Pain Chronic PainPhysiological: protective (survival Pathological: non-protective (nobenefit) survival benefit)Causes external: obvious Causes internal: obscureTissue damage: resolution within CNS changes: may not resolvedays/weeksAttended by physicians (illness) Attended by clergy (suffering)Symptom of illness Existential: a social phenomenonThe demon is outside The demon is within
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”.
“A WAY OF LIFE” IN OUR SOCIETY• Destitution, Poverty, Homelessness affect health, yet are not being addressed by medical science (a way of life).
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).
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
A “PERFECT STORM” OF CONTROVERSY*War on pain*War on drugs• Physicians are beingenlisted on both fronts: -combating pain -reducing the risk of diversion, abuse and addiction.
PHARMACOVIGILENCE• The science of detecting, understanding and preventing adverse effects or any other drug related problem.
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).
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 experiencepain is to have certainty.(Elaine Scarry: The Body in Pain)
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
ALLODYNIA AND HYPERALGESIA Allodinia = Pain evoked by innocuous stimuli. Hyperalgesia = exaggerated pain produced by mildly painful stimuli.
NOCICEPTION (THE AFFERENTS)-A beta fibers respond only to non-noxious stimuli-A delta and C fibers respond to noxious mechanical, heat, andchemical stimuli.Stephen M. Stahl;Stahl’s Essential Psychopharmacology; Third Edition;Cambridge University Press 2008
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.
THE PHYSIOLOGY OF INSULAR CORTEXThe insulae are believed to be involved in:• emotion• pain• empathy• perception,• self-awareness,• cognitive functioning,• interpersonal experience.
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
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
PERIPHERAL SENSITIZATION LEADS TO CENTRAL SENSITIZATION
CENTRAL SENSITIZATION (SECONDARY HYPERALGESIA)
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.
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
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
FUNCTIONAL SOMATIC SYNDROMES (FSS)• Fibromyalgia• Irritable bowel syndrome• Chronic Fatigue Syndrom• Temporomandibular Joint Disorder• Interstitial cystitisPatients with one FSS often suffer from one or moreother FSS as well as psychiatric comorbidity.
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
PAIN PATIENTS IN PSYCHIATRIC PRACTICE Psychiatrist: Somatization d/o Rheumatologist: fibromyalgia Neurologist: chronic fatigue syndrome/myalgic encephalomyelitis Patient: “multiple chemical sensitivities”
SNRI DRUGS APPROVED FOR CHRONIC PAINDuloxetine Milnacipran60 mg once daily; higher doses increase SEs 30-200 mg/day in 2 doseswithout increasing efficacy in pain disordersApproved for multiple neuropathic pain Approved for fibromyalgiadisordersSEs include nausea, dry mouth; can cause SEs: nausea, constipation, sweating, urologicurinary retention, rare activation of suicidality, complaints, urinary hesitancy, dose-dependent increase in blood pressure; can cause rare activationrare hepatotoxicity of suicidalityMetabolized by CYP 450 2D6 Few known adverse pharmacokinetic drug interactionsNot for use with Thioridazine, MAOIs, or Not for use with MAOIs, or patients with uncontrolledpatients with uncontrolled narrow angle narrow angle glaucoma or hepatic impairmentglaucoma or hepatic impairment
OTHER SNRI DRUGSVenlafaxine Desvenlafaxine75-225 mg once daily 50 mg once dailyClinical efficacy in reducing chronic pain Clinical efficacy in reducing chronic painSEs include headaches, insomnia, nausea, SEs include insomnia, nausea, constipation,sweating, dose dependent increase in BP, rare sweating, increase in BP, rare activation ofactivation of suicidality suicidality.Use with caution in patients with cardiac Use with caution in patients with cardiacimpairment impairmentNot for use with MAOIs or in patients with Not for use with MAOIs or in patients withuncontrolled narrow-angle glaucoma uncontrolled narrow-angle glaucoma
ALPHA 2 DELTA LIGANDSPregabalin Gabapentin150-600 mg/day in 2-3 doses 900-1800 mg/day in 3 dosesApproved in multiple neuropathic Approved in postherpeticpain disorders neuralgiaMost common SEs: sedation, Most common SEs: sedation,dizziness dizziness, fatigue, ataxia, nystagmus, tremorEnhances slow-wave sleep Enhances slow-wave sleepRenally excreted Renally excreted
ANTICONVULSANTS FOR CHRONIC PAINCarbamazepine Oxcarbazepine Topiramate Lamotrigine Zonisamide1200 mg/day; 1200-1400 50-300 mgday 100-300 mg/day 100-600 mg/daystart slow mg/day; start slowApproved for Adjunct for FDA approved Clinical efficacy Some clinicaltrigeminal neuropathic for migraine in neuropathic efficacy inneuralgia; may pain prophylaxis pain neuropathichave efficacy in pain andother migrainesneuropathicpain disordersInduces P450 Less Induction of May have Efficacy canenzymes, may P450 enzymes efficacy in other wane afterlower the levels neuropathic several weeks ofof other drugs pain disorders. use
TRICYCLICS FOR CHRONIC PAINAmytriptiline Cyclobenzaprine25-50 mg once daily 15 mg/day in 3 dosesUsed for multiple pain disorders 15-30 mg/day in one dose (ER)SEs include sedation, weight gain, Muscle relaxantanticholinergic effects, dizziness, hypotensionMetabolized to nortriptyline by CYP 450 1A2 Not recommended for long term useSignificant drug-drug interactions SEs: sedation, dry mouth, fatigue headacheUse with caution in patients with renal or Use with caution in patients with urinaryhepatic impairment retention, angle-closure glaucoma, hepatic impairmentCan have cardiovascular effects Can have cardiovascular effectsMultiple contraindications Do not use with MAOIs
ON THE OPIOID BORDER:PROPOXYPHENE AND TRAMADOL
OTHER PAIN AGENTSNSAIDs Acetaminophen BaclophenBetter for acute pain Less effect on bleeding Muscle relaxant andor for chronic and renal function antispasticinflammatory pain compared to NSAIDsWarning for GI Can cause Used for trigeminalbleeding with SSRIs hepatotoxicity at high neuralgia and some doses other neuropathic pain conditionsCombination with Many psychotropics Use with caution inlithium may cause are metabolized by patients with renallithium toxicity the same liver enzymes impairment
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
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
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 maybe low• Aerobic exercise
EVIDENCE BASED TREATMENT OF CHRONICPAIN SYNDROMES WITH HIGH PSYCHIATRIC CO-MORBIDITY 1. Neuropathic Pain 2. Fibromyalgia 3. Chronic Back Pain 4. Osteoarthritis
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
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
DIAGNOSTIC CRITERIA FOR FIBROMYALGIAAmerican 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
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
FIBROMYALGIA - PHARMACOLOGIC AND NON- PHARMACOLOGIC TREATMENTSFirst line:• SNRIs (Duloxetine, Milnacipran)• Alpha2 Delta ligands (Pregabalin, Gabapentin)• Aerobic Exercise• CBT• EducationSecond line:• TCAs• Cyclobenzaprine (chemical structure related to TCAs)• TramadolSchatzberg A, Nemeroff C; Textbook of Psychopharmacology; The American Psychiatric Publishing, 2009
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
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 intervertebraldiscs in the spine, a common cause of lower back pain.
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