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Update on Fibromyalgia and Postherpetic Neuralgia Steven Stanos , DO

Update on Fibromyalgia and Postherpetic Neuralgia Steven Stanos , DO. Fibromyalgia Pathophysiology. Abeles AM, et al. Ann Intern Med . 2007;146:726-734. Fibromyalgia Possible Spinal and Supraspinal Effects. Descending Modulation. Facilitation Substance P Glutamate and EAAs NGF.

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Update on Fibromyalgia and Postherpetic Neuralgia Steven Stanos , DO

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  1. Update on Fibromyalgiaand Postherpetic NeuralgiaSteven Stanos, DO

  2. FibromyalgiaPathophysiology Abeles AM, et al. Ann Intern Med. 2007;146:726-734.

  3. FibromyalgiaPossibleSpinal andSupraspinal Effects Descending Modulation Facilitation Substance P Glutamate and EAAs NGF • Inhibition • Descending anti-nociceptive pathways Norepinephrine and serotonin (5HT1a,b) Opioidsa Descendingmodulatory pathways Ascendingpathways a Recent evidence suggests reduced µ-opioid receptor availability in patients with fibromyalgia; the arrows refer to the pathologic state. Harris RE, et al. J Neurosci. 2007;27:10000-10006; Millan MJ, et al. Prog Neurobiol. 2002;66:355-474.

  4. Fibromyalgia PathophysiologyHPA Axis and Psychological Stress Connection “TRIGGER EVENT”Psychological Distress ALTERED HPA AXIS FUNCTION Geneticfactors ↓CRH ↓ACTH ↓Cortisol Fibromyalgia Genetics ↓ Serotonin Pain ↑ Substance P McBeth J, et al. Arthritis Rheum. 2007;56:360-371.

  5. FibromyalgiaOverlap With Related Syndromes CFS1% of population; fatigue and 4 of 8 “minor criteria” Fibromyalgia 2%-4% of population; defined by widespread pain and tenderness Pain and/or sensory amplification Psychiatric disordersMDD, OCD, bipolar, PTSD, GAD, panic attack Regional pain syndromes (eg, tension headache,TMD, idiopathic LBP) Somatoform disorders4% of population; multiple unexplained symptoms,no “organic” findings CFS, chronic fatigue syndrome; GAD, generalized anxiety disorder; LBP, low back pain; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; PTSD, post-traumatic stress disorder; TMD, temporomandibular disorders. Clauw DJ, et al. Neuroimmunomodulation. 1997;4:134-153.

  6. FibromyalgiaShared Features With Depression • Strong genetic predisposition and similar comorbidity • Coaggregation in families • Cognitive disturbances • Dysfunction of the HPA axis • Chronic stress-induced cytokine expression in the brain • Central monoaminergic neurotransmission http://www.medscape.com/viewprogram/17278_pnt. FPO

  7. FibromyalgiaRecommended Diagnostic Work-up History of chronic,widespread pain for ≥ 3 months Rule out other conditions that may present with chronic widespread pain (very much “operator dependent”) General physical exam, neurologic exam, selected laboratory testing (ESR, thyroid tests, avoid screening serologic tests) Sleep and mood evaluation Confirm presence of tender points(Need 11of 18) Confirm diagnosis of fibromyalgia ESR=erythrocyte sedimentation rate. Adapted from: Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children; 2005 http://www.medscape.com/viewprogram/17278_pnt. FPO

  8. FibromyalgiaDifferential Diagnosis • Rheumatic illness • Systemic CTD (RA, myositis, SLE, PMR) • False + ANA “pitfalls” • Seronegative spondyloarthropathies • Other chronic pain disorder (OA, spinal stenosis, neuropathy) • Infectious disease • Lyme disease • Viral (hepatitis C, HIV, “EBV”) • Hypothyroidism • Consider concurrent systemic illness and primary sleep and mood disorders CTD=connective tissue disease. RA=rheumatoid arthritis. SLE=systemic lupus erythematosus; PMR=polymyalgia rheumatica; ANA=antinuclear antibodies; HIV=human immunodeficiency virus; EBV=Epstein-Barr virus.http://www.medscape.com/viewprogram/17278_pnt. FPO

  9. FibromyalgiaStepwise Treatment Algorithm Step 1. Confirm diagnosis of fibromyalgia a. Identify important symptom domains, their severity, and level of patient function b. Evaluate for comorbid medical and psychiatric disorders(eg, sleep apnea, OA, anxiety disorder) c. Assess psychosocial stressors, level of fitness, and barriers to treatment d. Provide education about fibromyalgia e. Review treatment options Step 2. Recommend treatment based on the individual evaluation a. As a first-line approach for patient with moderate to severe pain, trail with evidence-based medications, such as SSNRI (not for patients with bipolar disorder), α2δ ligand (especially for patients with prominent sleep disturbance and anxiety),or, if these do not work, SSRI or TCA b. Evaluate for comorbid medical and psychiatric disorders(eg, sleep apnea, OA, anxiety disorder) Step 3. If not responding to medication alone, considerCBT or group education a. Encourage exercise according to fitness level (eg, goal of 30 to 60 minutes of low-moderate intensity aerobic exercise [e.g., walking, pool exercises, stationary bike]at least 2 to 3 times a week) b. Encourage participation in supervised or group exercise Arnold LM. Arthritis Res Ther. 2006;8:212.

  10. FibromyalgiaPossible Two Types Fibromyalgia-Type I (n=27) Fibromyalgia-Type I (n=34) Heterogeneity is largely due to differences in depressive and anxiety symptoms 10 8 6 Visual Analog Scale 4 2 0 Pain Tiredness Anxiety Depression Stiffness Morning Fatigue de Souza JB, et al. Rheumatol Int. 2008 Sep 27. [Epub ahead of print].

  11. Short/Short subgroup showed higher mean levels of depression and psychological distress Polymorphism also associated with anxiety-related personality traits, diarrhea-predominant IBS, and MDD Additional linkage between fibromyalgia and a SNP in the serotonin 2A receptor gene (5-HT2A) FibromyalgiaGenetic Influences Serotonin-Related Genes a Gene Frequency, % Genotype at a SNP in the regulatory promoter region of the serotonin transporter gene (5-HTT) a P=0.046.SNP, single nucleotide polymorphism.Bondy B, et al. Neurobiol Dis. 1999;6:433-439; Cohen H, et al. Arthritis Rheum. 2002;46:845-847; Hoefgen B, et al. Biol Psychiatry. 2005;57:247-251; Offenbaecher M, et al. Arthritis Rheum. 1999;42:2482-2488; Yeo A, et al. Gut. 2004;53:1452-1458.

  12. FibromyalgiaGenetic Influences (cont’d) • Dopamine D4-receptor exon III repeat polymorphism • Decreased frequency of 7-repeat allele in fibromyalgia • Also associated with low novelty-seeking personality • Altered dopamine D2-receptor function in fibromyalgia • Catechol-O-methyltransferase (COMT) • 1 of several enzymes that degrade catecholamines • Dopamine, epinephrine, norepinephrine • 1 variant associated with diminished µ-opioid system responses, higher sensory and affective ratings of pain, and more negative affective state Dopamine- and Catecholamine-Related Genes Buskila D, et al. Mol Psychiatry. 2004;9:730-731; Gürsoy S, et al. Rheumatol Int. 2003;23:104-107; Malt EA, et al. J Affect Disord. 2003;75:77-82; Zubieta JK, et al. Science. 2003;299:1240-1243.

  13. FibromyalgiaFamily Study • OR of fibromyalgia in a relative of fibromyalgia proband vs fibromyalgia in a relative of RA proband was 8.5a • Primarily due to the effect of female relatives • Relatives of fibromyalgia probands showed increased tender point scores and decreased myalgic scores compared with relatives of RA probandsb a 95% confidence interval 2.8–26; P=0.0002. bP<0.0001 for both comparisons. OR, odds ratio. Arnold LM, et al. Arthritis Rheum. 2004;50:944-952.

  14. Lower mechanical and thermal pain thresholds (allodynia) High pain ratings for noxious stimuli (hyperalgesia) Altered temporal summation of painful stimuli (wind-up) Fibromyalgia Enhanced Pain Processing NC-3sec NC-5sec 70 FM-3sec FM-5sec 60 50 40 Pain Ratings, 0-100 30 20 10 0 T1 T5 T10 T15 3sec, interstimulus intervals of 3 sec; 5sec, interstimulus intervals of 5 sec; FM, fibromyalgia patient;NC, normal control; T, tap stimulus. Geisser ME, et al. Pain. 2003;102:247-254; Petzke F, et al. Pain. 2003;105:403-413; Staud R. Arthritis Res Ther. 2006;8:208-214; Staud R, et al. Pain. 2001;91:165-175.

  15. FibromyalgiafMRI Findings 14 12 10 8 Pain Intensity 6 Fibromyalgia 4 Subjective pain control 2 Stimulus pressure control 0 1.5 2.5 3.5 4.5 Stimulus Intensity, kg/cm2 Similar pressure produced significantly greater activation at 13 regions in the patient group and 1 region in the control group fMRI, functional magnetic resonance imaging. N=16 patients with fibromyalgia and 16 matched controls.Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.

  16. Case StudyIntroducing Katherine • 54-year-old financial consultant • Presents to PCP for evaluation of pain that started 4 months ago in her shoulders and spread recently toher hips, arms, and back • Pain levels vary, 5-8/10 • She can’t work as efficiently as before • History of symptoms consistent with IBS for the last 3 years, and recent depression, poor sleep andchronic fatigue • PCP suspects SLE, RA, or fibromyalgia • What formal diagnostic, laboratory, and imaging tests may be helpful when diagnosing Katherine? • Does she have any fibromyalgia predisposing factors? IBS, irritable bowel syndrome; PCP, primary care physician; RA rheumatoid arthritis; SLE, systemic lupus erythematosus.

  17. FibromyalgiaComprehensive Assessment Detailed history focusing on illness that may mimic, complicate, or occur concurrently with fibromyalgia Evaluate the severity of other fibromyalgia symptoms: fatigue, sleep disturbance, mood/cognitive disturbance Patient with probable fibromyalgia Clinical diagnosis of fibromyalgia based on 1990 ACR criteria Assess functional status at initial and subsequent visits Characterize pain type, location, source, intensity, duration, effects on QoL Analyze complete blood count, ESR, muscle enzymes, liver function, thyroid function ACR, American College of Rheumatology; ESR, erythrocyte sedimentation rate; QoL, quality of life. Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Glenville, Ill: American Pain Society; 2005.

  18. FibromyalgiaACR Diagnostic Criteria • History (≥3 months) of widespread pain • Above and below the waist • Bilateral • In the axial skeleton • Manual tenderpoint examination • Pain in ≥11 of 18 specific fibromyalgia tender points on digital palpation • ~ palpation force: 4 kg/1.4 cm2 Okifuji A, et al. J Rheumatol. 1997;24:377-383. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. http://www.fibromyalgia-symptoms.org/fibromyalgia_diagnosis.html. Accessed August 1, 2008.

  19. Key Fibromyalgia DomainsPatient Perspectives • Physical • Pain • Fatigue • Disturbed sleep • Emotional/cognitive • Depression, anxiety • Cognitive impairment (decreased concentration, disorganization • Memory problems • Social • Disrupted family relationships • Social isolation • Disrupted relationships with friends • Work/activity • Reduced activities of daily living • Reduced leisure activities/avoidance of physical activity • Loss of career/inability to advance in career or education Arnold LM, et al. Patient Educ Couns. 2008;73:114-120.

  20. KatherineDiagnosis • Based on normal laboratory results and comprehensive examination, PCP rules out RA,PMR, and SLE • Digital palpation reveals pain at 14 of the 18 tender points • She reports having trouble concentrating • PCP diagnoses fibromyalgia, recommends a support group, and provides educational material to help Katherine understand the disease Would your treatment plan differ if Katherine reported 9 of 18 tender points? Are cognitive deficits common in patients with fibromyalgia? PMR, polymyalgia rheumatica.

  21. FibromyalgiaCognitive Dysfunction 30 30 4 3 20 20 2 d’ Recalled Words Correct Responses 10 10 1 Free Recall Recognition Memory Working MemoryCapacity 80 80 160 60 60 120 Summed Score From Speed Tasks Number of Words Produced 40 40 80 Correct Answers 20 20 40 Verbal Fluency Verbal Knowledge Information-ProcessingSpeed Age-matched controls Older subjects Fibromyalgia patients a a a b a aP<0.05 compared with age-matched controls; bP=0.055 compared with age-matched controls.d’, a measure of how effectively a subject can discriminate an item as new or previously studied. N=23 fibromyalgia patients, 23 age-matched controls, and 22 education-matched controls who were 20 years older. Park DC, et al. Arthritis Rheum. 2001;44:2125-2133.

  22. FibromyalgiaDually Focused Treatment • Symptoms of pain, fatigue, etc • Nociceptive processes • Neuroendocrine and sleep dysfunction • Disordered sensory processing • Functional consequences of symptoms • Increased distress • Decreased activity • Isolation • Poor sleep • Maladaptive illness behaviors Pharmacologic therapies to improve symptoms Nonpharmacologic therapies to address dysfunction Clauw DJ, et al. Best Pract Res Clin Rheumatol. 2003;17:685-701(B).

  23. FibromyalgiaInterventions Patient Education Explain what the condition is and what it is not Physical Therapy Exercise programs CAM Cognitive-behavioral, alternative therapies Multimodal TherapeuticStrategies for Fibromyalgia Psychological SupportPsychotherapy, support groups Pharmacotherapy SNRIs, TCAs, anticonvulsants, tramadol Address Comorbidities Sleep dysfunction, depression, anxiety CAM, complementary and alternative medicine; SNRI, serotonin–norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant. Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Glenville, Ill: American Pain Society; 2005.

  24. Strong evidence Education Aerobic exercise Cognitive-behavioral therapy Modest evidence Strength training Hypnotherapy, biofeedback, balneotherapy Weak evidence Acupuncture Chiropractic, manual, and massage therapy Electrotherapy Ultrasound No evidence Tender point injections Flexibility exercise Fibromyalgia Nonpharmacologic Therapies Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Glenville, Ill: American Pain Society; 2005; Goldenberg DL, et al. JAMA. 2004;292:2388-2395.

  25. Benefits first reported 30 years ago Nearly universally beneficial Tolerance, compliance, and adherence are biggest hurdles Programs should be individualized Begin several months after pharmacologic therapy Begin with low-impact exercises FibromyalgiaAerobic Exercise Exercise Control a 30 25 a 20 15 Mean Change in Parameter, % 10 5 0 -5 -10 Aerobic Mean Tender Performance Point Pain Pain Intensity Threshold aP<0.001; meta-analysis of 4 independent studies. Busch AJ, et al. Cochrane Database Syst Rev. 2002, Issue 2. Art. No. CD003786. doi:10.1002/14651858.CD003786. McCain GA, et al. Arthritis Rheum. 1988;31:1135-1141.

  26. Longitudinal trials show reduced pain severity and improved function Systematic reviews demonstrate reduced pain and fatigue, improved mood and function Improvements also seen with meditation, relaxation, stress management Effects depend heavily on therapist and program FibromyalgiaCognitive-Behavioral Therapy Thoughts PhysicalResponse Feelings Behavior Goldenberg DL, et al. JAMA. 2004;292:2388-2395. Hadhazy V, et al. J Rheumatol. 2000;27:2911-2918. Williams DA. Best Pract Res Clin Rheumatol. 2003;17:649-665.

  27. FibromyalgiaCBT vs Routine Care 30 CBT (n=62) Routine (n=60) 25 20 15 % of Patient Responses 10 5 0 Physical Functioning or 2.9, p<0.05 Sensory Pain Affective Pain *Statistically significant. OR=odds ratio. Williams DA, et al J Rheumatol. 2002; 29(6):1280-1286. http://www.medscape.com/viewprogram/17278_pnt. FPO

  28. Strong evidence Dual-reuptake inhibitors Tricyclic compounds SNRIs Anticonvulsants Modest evidence Dopamine agonists Gamma hydroxybutyrate Tramadol SSRIs Weak evidence Growth hormone 5-hydroxytryptamine Tropisetron SAMe No evidence Opioids Corticosteroids NSAIDs Benzodiazepine and nonbenzodiazepine hypnotics Fibromyalgia Pharmacologic Therapies NSAID, nonsteroidal anti-inflammatory drug; SAMe, S-adenosyl-L-methionine; SSRI, selective serotonin reuptake inhibitor. Modified from: Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Glenville, Ill: American Pain Society; 2005; Goldenberg DL, et al. JAMA. 2004;292:2388-2395.

  29. FibromyalgiaDual-Uptake Inhibitors:TCAs Outcome Measure • TCAs associated with effect sizes substantially larger than 0 for all measurements • Largest improvements in sleep quality • Most modest improvements in stiffness, tenderness • Common AEs include sedation, anticholinergic side effects, weight gain 1.5 1.0 Effect Size, Standard Deviation 0.5 0.0 -0.5 Patient Global Assessment M.D. Global Assessment Tenderness Stiffness Fatigue Sleep Pain AE, adverse event. Box plot of effect size in 9 controlled studies of TCA treatment of fibromyalgia. Observations lying beyond the 5th and 95th percentiles. Arnold LM, et al. Psychosomatics. 2000;41:104-113.

  30. FibromyalgiaDual-Uptake Inhibitors:Cyclobenzaprine • Often classified as muscle relaxant, but actually structurally a tricyclic compound • Moderate improvements noted for sleep after 4, 8, and 12 weeks of treatment • Modest improvement in pain levels observed only at 4 weeks • Common AEs include sedation, anticholinergic side effects, and weight gain Favors Placebo Favors Treatment Bennett (1988) Carette (1994) Quimby (1989) Overall (95% Cl) 3.0 (95% CI: 1.6-5.7) 0 1 25 Effect Size on Dichotomous Outcomes of Improvement CI, confidence interval.Tofferi JK, et al. Arthritis Rheum. 2004;51:9-13.

  31. FibromyalgiaDual-Uptake Inhibitors:SNRIs • Do not interact with adrenergic, cholinergic, or histaminergic receptors, or sodium channels • Duloxetine • FDA approved for fibromyalgia, GAD, MDD, and pain associated with DPN • Venlafaxine • FDA approved for GAD, social anxiety disorder, MDD, and panic disorder • Ineffective in an RCT for fibromyalgia • Milnaciprana Duloxetine Venlafaxine Milnacipran a New Drug Application submitted to the FDA for fibromyalgia. Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Glenville, Ill: American Pain Society; 2005.

  32. FibromyalgiaSNRIs:Proposed MOA • Inhibition • Augmented descending inhibition via amplification of norepinephrine and serotonin signaling Perception Modulation Descendingmodulatory pathways Transduction Ascendingpathways Transmission MOA, mechanism of action.

  33. FibromyalgiaDuloxetine in Randomized Trials Mean DifferenceIV, Fixed, 95% CI 1.07 (0.66, 1.47) 2 -2 -1 0 1 Favours placebo Favors duloxetine 120 mg Mean DifferenceIV, Fixed, 95% CI Arnold (2005) Russell (2008) Overall (95% Cl) 0.89 (0.49, 1.30) 2 -2 -1 0 0 1 Favours placebo Favors duloxetine 60 mg Sultan A. BMC Neurology. 2008;8:29.

  34. FibromyalgiaAnticonvulsants:2 Ligands α2 N γ δ α1 N c c c • Drugs that diminish neuronal excitability • Bind to 2 subunit of voltage-gated calcium channels • Reduce calcium influx, thereby inhibiting neurotransmitter release • FDA indications • Fibromyalgia (pregabalin) • Neuropathic pain associated with DPN (pregabalin) • PHN (gabapentin, pregabalin) • Adjunctive therapy for partial-onset seizures in adults (pregabalin) or adults and children (gabapentin) Arnold LM, et al. Arthritis Rheum. 2007;56:1336-1344; Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273; Van Petegem F, Minor DL. Biochem Soc Trans. 2006;34:887-893.

  35. Significant improvements seen in MOS-sleep problem index, total SF-MPQ score, MAF global fatigue index, 4 SF-36 domains Common AEs (>10%) in the 450 mg-per-day group: dizziness, somnolence, headache, dry mouth, and peripheral edema Fibromyalgia Anticonvulsants:Pregabalin a >30% responders, % Pregabalin Dose, mg/d aP=0.003 compared with placebo after 8 weeks of treatment using 0-10 pain scores (N=529). MAF, multidimensional assessment of fatigue; MOS, medical outcomes study; SF-MPQ, McGill Pain Questionnaire-Short Form. Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273.

  36. FibromyalgiaPregabalin/Gabapentin:Proposed MOA • Facilitation • Decrease substance P release in inflammatory states • Inhibit substance P–induced glutamate release Perception Modulation Descendingmodulatory pathways Transduction Ascendingpathways Transmission Fehrenbacher JC, et al. Pain. 2003;105:133-141; Maneuf YP, et al. Pain. 2001;93:191-196.

  37. KatherineFollow-Up • Pain has increased in the 2 weeks since last visit to PCP • Stopped working • Rarely leaves the house because of depression • Despite spending much of the day in bed, Katherine reports feeling tired and run-down • Based on Katherine’s presentation, how would you proceed with her treatment? • In addition to treatment of pain, should Katherine be prescribed medication for any other condition? • What would constitute “successful” treatment?

  38. FibromyalgiaInterdisciplinary Pain Management Integrated and Coordinated Pain Specialist Nurses Primary Clinician Psychiatrist Spine Surgeon Neurologist Pharmacist Physiatrist Social Worker Psychologist Anesthesiologist Occupational Therapist Physician Assistant Physical Therapist

  39. FibromyalgiaConclusions • Wide range of data support the notion that fibromyalgia is a chronic pain disorder characterized by augmented central pain processing • Diagnosis should be based on ACR criteria, comprehensive assessment, exclusion of other potential disorders associated with widespread pain, and evaluation of the range of symptomology • Due to its complexity, it is best understood from amultidisciplinary perspective • To address pain and relevant comorbidities, treatment should include both pharmacologic and nonpharmacologic modalities

  40. Case: Ms. Karibean • 82 year old female. Chronic left abdominal pain. Rash from “insect bite” she suffered while on a cruise healed 4 months ago. Increase pain and sensitivity to light touch from clothing in same area. Pain worse at night, difficulty falling asleep and frequent awakenings due to pain. • Ibuprofen, Tylenol #3 not working.

  41. Primary Infection, Latency, and Recurrence of Varicella Zoster Virus 3. Varicella infection (chickenpox) 1. Entry 4. Latency (sensory ganglion) 2. Spread 5. Herpes zoster (shingles) Straus SE, et al. In: Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill Professional; 2003:2070-2080.

  42. The Spectrum of Pain in Herpes Zoster Rash Onset Prodrome Onset Pain Cessation Rash Healed Typically ≤1 wk 2-4 wk Can Be Years Acute pain Postherpetic neuralgia (PHN) 1 mo 3 mo 6 mo Irving GA, Wallace MS. In: Pain Management for the Practicing Physician. New York, NY: Churchill Livingstone; 1997:141-147. Bowsher D. J Pain Symptom Manage.1996;12:290-299.

  43. Pain Distribution in PHN Thoracic dermatomes are affected in the majority of patients (>50%) Other dermatomes are affected less often Trigeminal dermatome Lumbar dermatome Cervical dermatome Straus SE, et al Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill Professional; 2003.

  44. Considerations for Comprehensive Management Biologic intervention Pharmacologic and/or nonpharmacologic approaches Psychological intervention Address mood and sleep disturbances Enhance coping skills Social/rehabilitative intervention Family/social support Address work issues Physical rehabilitation Physical/occupational therapy Home exercise program

  45. Some Treatment Considerations in Neuropathic Pain of PHN • Patient Factors1,2 • Comorbidities • Mental status • Risks of drug misuse/ abuse • Risks of unintentionaloverdose • Adherence • Prior therapies • edication costs • Drug Factors1,2 • Efficacy • Safety • Potential for AEs • Tolerability • Drug interactions • Monotherapy vs.combination therapy • Treatment costs AEs=adverse events.1. Dworkin RH, et al. Pain. 2007;132:237-251. 2. Gilron I, et al. CMAJ. 2006;175:265-275.

  46. Evidence-Based Medications for Neuropathic Pain of PHN *Only lidocaine patch 5%, gabapentin, and pregabalin have indications specific for the treatment of PHN pain. Dworkin RH, et al. Pain. 2007;132:237-251.

  47. Lidocaine Patch 5%: Blood Levels Various Applications 5 4 3 µg/mL 2 1 0 Lidocaine* patch 5% 2 mg/min Infusion 2 g of 5% Cream to Burns Arthroscopic Knee Surgery Antiarrhythmic Level Toxic Level *In normal, healthy volunteers

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