Management of
Neuropathic Pain
Perry G. Fine, MD
Professor of Anesthesiology
Pain Research Center
School of Medicine
Unive...
Pathophysiology of
Neuropathic Pain
• Chemical excitation of non-nociceptors
• Recruitment of nerves outside of site of in...
Multiple Pathophysiologies May Be Involved
in Neuropathic Pain
• More than one mechanism of action likely involved
• Neuro...
Pain Treatment Continuum
Least
invasive
Most
invasive
Psychological/physical approaches
Topical medications
*Consider refe...
Nonpharmacologic Options
• Biofeedback
• Relaxation therapy
• Physical and occupational therapy
• Cognitive/behavioral str...
Dorsal
Horn
BRAIN
Pharmacologic Agents
Affect Pain Differently
Descending Modulation
Peripheral
Sensitization
Central Sens...
Mechanisms of Action:
Analgesic Agents
• Anticonvulsants
– sodium-channel blockade (oxcarbazepine [Trileptal])
– calcium-c...
FDA-Approved Treatments
for Neuropathic Pain
• Carbamazepine
– trigeminal neuralgia
• Duloxetine
– peripheral diabetic neu...
Treatment Guidelines for Diabetic Peripheral
Neuropathic Pain
Reason for
Agent Type Recommendation Agent Names
First tier ...
Interventional Treatments
for Neuropathic Pain
• Neural blockade
– sympathetic blocks for CRPS-I and II (reflex sympatheti...
Comparison of Neuropathic Pain Treatment
Guidelines, Excluding Trigeminal Neuralgia*
Medication Class
NeuPSIG
Guidelines
C...
Efficacy of Anticonvulsants in Treating
Neuropathic Pain: Older Anticonvulsants
Condition Carbamazepine Oxcarbazepine Phen...
Efficacy of Anticonvulsants in Treating
Neuropathic Pain: Newer Anticonvulsants
Condition Lamotrigine Vigabatrin Tiagabine...
Efficacy of Anticonvulsants in Treating
Neuropathic Pain: GABA Analogs
GABA = gamma aminobutyric acid. GBP = gabapentin.
A...
Are Serotonergic Antidepressants Effective in
Diabetic Peripheral Neuropathic Pain (DPNP)?
Author,
Year
Number
of
Patients...
Are TCAs Effective in DPNP?
Author,
Year
Number of
Patients
Active
Drug
Dose
(mg/day)
Placebo
Controlled?
Effective for
Pa...
Is Venlafaxine Effective in DPNP?
VEN = venlafaxine. XR = extended release.
Author,
Year
Number of
Patients
Active
Drug
Do...
Is Duloxetine Effective in DPNP?
Author,
Year
Number of
Patients
Active
Drug
Dose
(mg/day)
Placebo
Controlled?
Drug
Effect...
Head-to-head Trials for
DPNP: Antidepressants vs Anticonvulsants
Author,
Year
Number of
Patients
Active
Drug
Dose
(mg/day)...
Head-to-head Trials for DPNP:
Antidepressants vs Antidepressants
CIT = citalopram. DESIP = desipramine. FLUOX = fluoxetine...
NNTs for Anticonvulsants vs
Antidepressants in DPNP
• 12 trials of 9 antidepressants (including SSRIs)
• 4 trials of antic...
Consensus Treatment Guidelines for DPNP
Agent Type
Reason for
Recommendation
Agent Names
First tier >2 RCTs in DPNP
• Dulo...
First Tier: Duloxetine
• SNRI
• FDA-approved for DPNP
– 3 RCTs: 60-120 mg/day
– N=1139; 12 weeks
– Positive studies
FDA = ...
Study Duration Treatment Groups N
Duloxetine
60 mg/day
Duloxetine
120 mg/day
Goldstein DJ, et al.1* 12 weeks
20, 60, 120 m...
Adverse Events: Duloxetine
• Anorexia
• Asthenia
• Constipation
• Cough
• Decreased appetite
• Diarrhea
• Dizziness
• Dry ...
First Tier: Pregabalin
• α2-δ calcium channel modulator
• FDA-approved for DPNP
• 3 RCTs:
– 75 mg/day and 150 mg/day; same...
Adverse Events: Pregabalin
Most common reactions that
lead to discontinuation
• Dizziness
• Somnolence
• Asthenia
• Ataxia...
First Tier: TCAs
• Amitriptyline has been studied the most extensively
– Limitations due to anticholinergic adverse effect...
TCAs: Mechanisms
• Relief of pain through serotonin (5-HT) and norepinephrine (NE)
reuptake blockade1
• Blockade of -adre...
TCAs: Adverse Events
• Commonly reported AEs
(generally anticholinergic)
– Blurred vision
– Cognitive changes
– Constipati...
Postherpetic
Neuralgia
Efficacy of Pregabalin in PHN
*≥50% and ≥30% reduction from baseline. †P≥0.001 vs placebo. ‡600 mg/day arm stratified acco...
Pregabalin Improves Sleep
Disturbance in Patients with PHN
*P≤0.01 vs placebo.†600 mg/day arm stratified according to CLcr...
Efficacy of Gabapentin in PHN
RespondersatEndpoint(%)
25
30
35
40
45
50
PBO
0
Study 1
*P<0.01
**P<0.001
Study 2
GBP
3600 m...
Conclusions
• Irrespective of the neuropathic pain condition under treatment, the
central pathways involved in these condi...
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Management of Neuropathic Pain

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Presented by Dr.Perry Fine at Pain Management for the Elderly Course, 2010.
Scribe medical events Egypt. www.scribeofegypt.org

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Management of Neuropathic Pain

  1. 1. Management of Neuropathic Pain Perry G. Fine, MD Professor of Anesthesiology Pain Research Center School of Medicine University of Utah Salt Lake City, Utah
  2. 2. Pathophysiology of Neuropathic Pain • Chemical excitation of non-nociceptors • Recruitment of nerves outside of site of injury • Excitotoxicity • Sodium channels • Ectopic discharge • Deafferentation • Central sensitization – maintained by peripheral input • Sympathetic involvement • Antidromic neurogenic inflammation
  3. 3. Multiple Pathophysiologies May Be Involved in Neuropathic Pain • More than one mechanism of action likely involved • Neuropathic pain may result from abnormal peripheral nerve function and neural processing of impulses due to abnormal neuronal receptor and mediator activity • Combination of medications may be needed to manage pain: topicals, anticonvulsants, tricyclic antidepressants, serotonin- norepinephrine reuptake inhibitors, and opioids • In the future, ability to determine the relationship between the pathophysiology and symptoms/signs may help target therapy
  4. 4. Pain Treatment Continuum Least invasive Most invasive Psychological/physical approaches Topical medications *Consider referral if previous treatments were unsuccessful. Systemic medications* Interventional techniques* Continuum not related to efficacy
  5. 5. Nonpharmacologic Options • Biofeedback • Relaxation therapy • Physical and occupational therapy • Cognitive/behavioral strategies – meditation; guided imagery • Acupuncture • Transcutaneous electrical nerve stimulation
  6. 6. Dorsal Horn BRAIN Pharmacologic Agents Affect Pain Differently Descending Modulation Peripheral Sensitization Central Sensitization PNS Local Anesthetics Topical Analgesics Anticonvulsants Tricyclic Antidepressants Opioids Anticonvulsants Opioids NMDA-Receptor Antagonists Tricyclic/SNRI Antidepressants Anticonvulsants Opioids Tricyclic/SNRI Antidepressants SPINAL CORD CNS
  7. 7. Mechanisms of Action: Analgesic Agents • Anticonvulsants – sodium-channel blockade (oxcarbazepine [Trileptal]) – calcium-channel blockade (gabapentin) • Antidepressants – inhibit reuptake of norepinephrine and serotonin into presynaptic neurons (duloxetine) – sodium-channel blockade (tricyclics) • Opioids – block neurotransmitter-release by nociceptive fibers, thus decreasing transmission of pain-producing signals (oxycodone) • Topical Analgesics – sodium-channel blockade (lidocaine patch 5%) – vanilloid receptor (capsaicin)
  8. 8. FDA-Approved Treatments for Neuropathic Pain • Carbamazepine – trigeminal neuralgia • Duloxetine – peripheral diabetic neuropathy • Gabapentin – postherpetic neuralgia • Lidocaine Patch 5% – postherpetic neuralgia • Pregabalin – peripheral diabetic neuropathy – postherpetic neuralgia
  9. 9. Treatment Guidelines for Diabetic Peripheral Neuropathic Pain Reason for Agent Type Recommendation Agent Names First tier ≥2 RCTs in DPN Duloxetine, oxycodone CR, pregabalin, TCAs Second tier 1 RCT in DPN and ≥1 in other painful neuropathies Carbamazepine, gabapentin, lamotrigine, tramadol, venlafaxine ER (Effexor) Topical Mechanism of action Capsaicin, lidocaine Other ≥1RCTs in other painful neuropathies or other evidence Bupropion (Wellbutrin), citalopram (Celexa), methadone (Dolophine), paroxetine (Paxil), phenytoin (Dilantin), topiramate (Topamax) Adapted from Argoff CE, et al. Mayo Clin Proc. 2006;81:S12-S25. CR = controlled release; DPN = diabetic peripheral neuropathy; ER = extended release RCT= randomized controlled trial; TCAs = tricyclic antidepressants.
  10. 10. Interventional Treatments for Neuropathic Pain • Neural blockade – sympathetic blocks for CRPS-I and II (reflex sympathetic dystrophy and causalgia) • Neurolytic techniques – alcohol or phenol neurolysis – pulse radio frequency • Stimulatory techniques – spinal cord stimulation – peripheral nerve stimulation • Medication pumps CRPS = complex regional pain syndrome.
  11. 11. Comparison of Neuropathic Pain Treatment Guidelines, Excluding Trigeminal Neuralgia* Medication Class NeuPSIG Guidelines CPS Guidelines EFNS Guidelines TCAs First line First line First line for PPN, PHN, and CP Calcium channel α2-δ ligands (gabapentin and pregabalin) First line First line First line for PPN, PHN, and CP SNRIs (duloxetine and venlafaxine) First line Second line Second line for PPN *Only nontopical medications and nonopioid drugs considered first- or second-line in 1 of the guidelines are presented. CP = central pain. CPS = Canadian Pain Society. EFNS = European Federation of Neurological Societies. NeuPSIG = Neuropathic Pain Special Interest Group. NP = neuropathic pain. PHN = postherpetic neuralgia. PPN = painful polyneuropathy. SNRI = serotonin-norepinephrine reuptake inhibitor. TCAs = tricyclic antidepressants. Adapted from: O’Connor AB, Dworkin RH. Am J Med. 2009;122:S22-S32.
  12. 12. Efficacy of Anticonvulsants in Treating Neuropathic Pain: Older Anticonvulsants Condition Carbamazepine Oxcarbazepine Phenytoin Sodium Valproate Diabetic neuropathy Yes (mod) ? (high) ? (mod) Yes (high) Postherpetic neuralgia Yes (mod) 0 0 Yes (high) Trigeminal neuralgia Yes (high) 0 0 0 Spinal cord injury pain 0 0 0 No (mod) Poststroke pain No (mod) 0 0 0 HIV neuropathy 0 0 0 0 Pain in patients with Guillain- Barré syndrome Yes (mod) 0 0 0 Cancer-related neuropathic pain 0 0 ? (mod/high) 0 Stomatodynia 0 0 0 0 TMJ dysfunction and associated myofascial pain 0 0 0 0 Chronic lumbar radicular pain 0 0 0 0 Postamputation phantom limb pain 0 0 0 0 Fibromyalgia syndrome 0 0 0 0 CRPS I 0 0 0 0 Neuropathic pain not otherwise specified ? (mod) 0 Yes (mod) No (high) CRPS = complex regional pain syndrome. HIV = human immunodeficiency virus. TMJ = temporomandibular joint. Adapted from: Goodyear-Smith F, Halliwell J. Clin J Pain. 2009;25:528-536.
  13. 13. Efficacy of Anticonvulsants in Treating Neuropathic Pain: Newer Anticonvulsants Condition Lamotrigine Vigabatrin Tiagabine Topiramate Levetiracetam Diabetic neuropathy ? (high) 0 0 No (high) 0 Postherpetic neuralgia 0 0 0 0 ? (low) Trigeminal neuralgia Yes (mod) 0 0 No (mod) 0 Spinal cord injury pain ? (high) 0 0 0 0 Poststroke pain Yes (high) 0 0 0 0 HIV neuropathy Yes* (high) 0 0 0 0 Pain in patients with Guillain-Barré syndrome 0 0 0 0 0 Cancer-related neuropathic pain 0 0 0 0 0 Stomatodynia 0 0 0 0 0 TMJ dysfunction and associated myofascial pain 0 0 0 0 0 Chronic lumbar radicular pain 0 0 0 No (mod) 0 Postamputation phantom limb pain 0 0 0 0 0 Fibromyalgia syndrome 0 0 0 0 0 CRPS I 0 0 0 0 0 Neuropathic pain not otherwise specified No (mod) 0 ? (mod) 0 0 *Efficacious in patients on antiretroviral therapy but evidence is inconclusive for patients not receiving antiretroviral therapy. Adapted from: Goodyear-Smith F, Halliwell J. Clin J Pain. 2009;25:528-536.
  14. 14. Efficacy of Anticonvulsants in Treating Neuropathic Pain: GABA Analogs GABA = gamma aminobutyric acid. GBP = gabapentin. Adapted from: Goodyear-Smith F, Halliwell J. Clin J Pain. 2009;25:528-536. Condition GBP Pregabalin Diabetic neuropathy Yes (high) Yes (high) Postherpetic neuralgia Yes (high) Yes (high) Trigeminal neuralgia 0 0 Spinal cord injury pain Yes (high) Yes (high) Poststroke pain 0 0 HIV neuropathy Yes (high) 0 Pain in patients with Guillain- Barré syndrome Yes (mod) 0 Cancer-related neuropathic pain Yes (high) 0 Stomatodynia 0 0 TMJ dysfunction and associated myofascial pain 0 0 Chronic lumbar radicular pain 0 0 Postamputation phantom limb pain Yes (high) 0 Fibromyalgia syndrome 0 Yes (high) CRPS I No (high) 0 Neuropathic pain not otherwise specified Yes (high) 0
  15. 15. Are Serotonergic Antidepressants Effective in Diabetic Peripheral Neuropathic Pain (DPNP)? Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled ? Effective for Pain? Goodnick P, et al. 2000 12 Sertraline 62 No Yes (100% patients) Goodnick P, et al. 1997 8 Sertraline 150 No Yes Wilson RC. 1999 31 Trazodone 50-100 No 22.6% complete relief and 61.3% symptomatic relief
  16. 16. Are TCAs Effective in DPNP? Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled? Effective for Pain? Sindrup RH, et al. 1989 9 IMI Variable Yes Yes Sindrup RH, et al. 1990 14 IMI Variable No Yes, if concentration >400-500 mmol/L Max MB, et al. 1987 29 AMI Variable Yes Yes Young RJ, Clarke BF. 1985 71 IMI or AMI Variable No Yes in 72.3% of patients Kvinesdal B, et al. 1984 12 IMI Variable Yes Yes Langohr HD, et al. 1982 48 CLO vs ASA 150 1500 Active Control Yes CLO>ASA Turkington RW. 1980 59 IMI and AMI 100 100 Active Control 100% response to drug vs 0% response to active control AMI = amitriptyline. ASA = acetylsalicylic acid. CLO = clomipramine. IMI = imipramine.
  17. 17. Is Venlafaxine Effective in DPNP? VEN = venlafaxine. XR = extended release. Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled? Effective for Pain? Davis JL, Smith RL. 1999 11 VEN 37.5-75 No 100% patients, 75-100% reduction in pain Lithner F. 2000 11 VEN 225 No Yes Kiayias J, et al. 2000 8 VEN 75 Yes Yes 100% patients Rowbotham MC, et al. 2004 244 VEN XR 75, 150, 225 vs placebo Yes Yes at 150 and 225 mg
  18. 18. Is Duloxetine Effective in DPNP? Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled? Drug Effective for Pain? Goldstein DJ, et al. 2005 457 Duloxetine 20, 60, 120 Yes Yes, at 60 and 120 mg
  19. 19. Head-to-head Trials for DPNP: Antidepressants vs Anticonvulsants Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled? Drug Effective for Pain? Dallocchio C, et al. 2000 13 GBP 12 AMI GBP vs AMI 2400 30-90 N/A GBP>AMI Morello CM, et al. 1999 27 GBP vs AMI 225 N/A GBP = AMI
  20. 20. Head-to-head Trials for DPNP: Antidepressants vs Antidepressants CIT = citalopram. DESIP = desipramine. FLUOX = fluoxetine. MAP = maprotiline. MIA = mianserin. Author, Year Number of Patients Active Drug Dose (mg/day) Placebo Controlled? Effective for Pain? Vrethem M, et al. 1997 37 AMI vs MAP 75 75 Yes Yes AMI>Map>Placeb o Max MB, et al. 1992 38 46 AMI vs DESIP vs FLUOX vs Placebo 105 111 40 Yes AMI = DESIP AMI>Placebo DESIP>Placebo FLUOX = Placebo Sindrup SH, et al. 1992 18 IMI vs MIA vs Placebo Variable 60 Yes IMI>Placebo MIA = Placebo Sindrup SH, et al. 1992 15 CIT vs IMI vs Placebo 40 Yes IMI>CIT>Placebo
  21. 21. NNTs for Anticonvulsants vs Antidepressants in DPNP • 12 trials of 9 antidepressants (including SSRIs) • 4 trials of anticonvulsants (phenytoin, carbamazepine, GBP) • NNT antidepressants = 3.4 • NNT anticonvulsants = 2.7 SSRI = selective serotonin reuptake inhibitor. Collins SL, et al. J Pain Symptom Manage. 2000;20:449-458.
  22. 22. Consensus Treatment Guidelines for DPNP Agent Type Reason for Recommendation Agent Names First tier >2 RCTs in DPNP • Duloxetine • Pregabalin • Oxycodone CR • TCAs Second tier 1 RCT in DPNP >1 RCT neuropathic pain • GBP • Tramadol • Lamotrigine • VEN XR CR = controlled-release. RCT = randomized controlled trial. Modified from: Argoff CE, et al. Mayo Clin Proc. 2006;81:S12-S25.
  23. 23. First Tier: Duloxetine • SNRI • FDA-approved for DPNP – 3 RCTs: 60-120 mg/day – N=1139; 12 weeks – Positive studies FDA = US Food and Drug Administration.
  24. 24. Study Duration Treatment Groups N Duloxetine 60 mg/day Duloxetine 120 mg/day Goldstein DJ, et al.1* 12 weeks 20, 60, 120 mg/day vs placebo 457 P<0.001** P<0.001** Wernicke JF, et al.2* 12 weeks + 1 week taper 60, 120 mg/day vs placebo 334 P<0.001** P<0.001** Raskin J, et al.3* 12 weeks + 1 week taper 60, 120 mg/day vs placebo 348 P<0.001** P<0.001** Duloxetine: Clinical Trials in DPNP Study Duration Treatment Groups N 1-year, open-label safety studies – extension of studies 1, 2, and 34* 52 weeks 120 mg vs routine care 867 6-month, open-label safety study5 28 weeks 60 mg BID vs 120 mg QD 449 *Patients with mood disorders excluded. **Duloxetine vs placebo on primary endpoint: 24-hour average pain severity in 12 weeks. †Duloxetine is not indicated for long-term treatment in DPNP; the efficacy beyond 12 weeks has not been systematically studied in placebo-controlled trials. 1. Goldstein DJ, et al. Pain. 2005;116:109-118. 2. Wernicke JF, et al. Neurology. 2006;67:1411-1420. 3.Raskin J, et al. Pain Med. 2005;6:346-356. 4. Hardy T, et al. Diabetes Care. 2007;30:21-26. 5. Raskin J, et al. Pain Med. 2006;7:373-385. Long-term Safety Studies† Short-term Efficacy and Safety Studies
  25. 25. Adverse Events: Duloxetine • Anorexia • Asthenia • Constipation • Cough • Decreased appetite • Diarrhea • Dizziness • Dry mouth • Dyspepsia • Erectile dysfunction • Fatigue • Headache • Hyperhidrosis • Insomnia • Loose stool • Muscle cramp • Myalgia • Nasopharyngitis • Nausea • Pharyngolaryngeal pain • Pollakiuria • Pyrexia • Somnolence • Tremor • Vomiting Observed in at least 3% of patients Gremillion SW, et al, eds. Drug Facts And Comparisons® Pocket Version 2010. St. Louis, MO: Wolters Kluwer; 2010.
  26. 26. First Tier: Pregabalin • α2-δ calcium channel modulator • FDA-approved for DPNP • 3 RCTs: – 75 mg/day and 150 mg/day; same as placebo – 300 mg/day and 600 mg/day; good efficacy Lesser H, et al. Neurology. 2004;63:2104-2110. Richter RW, et al. J Pain. 2005;6:253-260. Rosenstock J, et al. Pain. 2004;110:628-638.
  27. 27. Adverse Events: Pregabalin Most common reactions that lead to discontinuation • Dizziness • Somnolence • Asthenia • Ataxia • Blurred vision • Confusion • Incoordination • Peripheral edema • Abnormal thinking Most common reactions in controlled clinical trials • Blurred vision • Dizziness • Dry mouth • Edema • Somnolence • Abnormal thinking • Weight gain Gremillion SW, et al, eds. Drug Facts And Comparisons® Pocket Version 2010. St. Louis, MO: Wolters Kluwer; 2010.
  28. 28. First Tier: TCAs • Amitriptyline has been studied the most extensively – Limitations due to anticholinergic adverse effects • Constipation and pseudodementia – Potential cardiac conduction abnormalities1 • Nortriptyline and desipramine – Better adverse effect profiles – High doses cause anticholinergic side effects • Affects cardiac conduction – Desipramine is an alternative if patient has an amitriptyline intolerance2 1. Max MB, et al. Pain. 1991;45:3-9. 2. Duby JJ, et al. Am J Health Syst Pharm. 2004;61:160-173.
  29. 29. TCAs: Mechanisms • Relief of pain through serotonin (5-HT) and norepinephrine (NE) reuptake blockade1 • Blockade of -adrenergic receptors2 • Sodium and potassium channel modulation • Modulation of monoamine neurotransmitters • NMDA receptor antagonism? NMDA = N-methyl-D-aspartate 1. Lawson K. Expert Opin Investig Drugs. 2002;11:1437-1445. 2. Sindrup SH, Jensen TS. Pain. 1999;83:389-400.
  30. 30. TCAs: Adverse Events • Commonly reported AEs (generally anticholinergic) – Blurred vision – Cognitive changes – Constipation – Dry mouth – Orthostatic hypotension – Sedation – Sexual dysfunction – Tachycardia – Urinary retention – Weight gain Most AEs desipramine nortriptyline imipramine doxepin amitriptyline Fewest AEs AEs = adverse events
  31. 31. Postherpetic Neuralgia
  32. 32. Efficacy of Pregabalin in PHN *≥50% and ≥30% reduction from baseline. †P≥0.001 vs placebo. ‡600 mg/day arm stratified according to CLcr. Patients either CLcr >30 and ≤60 mL/min received 300 mg/day; patients with CLcr >60 mL/min received 600 mg/day. CLcr = creatinine clearance. van Seventer, RV et al. Curr Med Res Opin. 2006;22:375-384. Patients(%) 10 20 30 40 50 60 Responders (≥50%*) Placebo (n=93) Responders (≥30%*) 0 150 (n=87) 300 (n=98) 600‡ (n=98) 600‡ (n=98) Placebo (n=93) 150 (n=87) 300 (n=98) Pregabalin dose (mg/day) Pregabalin dose (mg/day) † ††† † Proportion of Responders to Treatment
  33. 33. Pregabalin Improves Sleep Disturbance in Patients with PHN *P≤0.01 vs placebo.†600 mg/day arm stratified according to CLcr patients with CLcr >30 and ≤60mL/min received 300 mg/day pregabalin; patients with CLcr >60 mL/min received 600 mg/day. van Seventer R, et al. Curr Med Res Opin. 2006;22:375-384. WeeklyMeanSleep InterferenceScore * 1 2 3 4 5 6 0 Endpoint Treatment (Weeks) Mean Weekly Pain-related Sleep-interference in PHN at All Doses 1 2 4 7 11 131210 Placebo (n=93) Pregabalin 150 mg/day (n=87) Pregabalin 300 mg/day (n=98) Pregabalin 600† mg/day (n=88) ********** * * * * * * * * * * * * * * **** * * * *** * * * * ** * 98653
  34. 34. Efficacy of Gabapentin in PHN RespondersatEndpoint(%) 25 30 35 40 45 50 PBO 0 Study 1 *P<0.01 **P<0.001 Study 2 GBP 3600 mg/day GBP 1800 mg/day GBP 2400mg/day PBO 12% * ** ** 20 15 10 5 29% 14% 32% 34% Proportion of Responders (Patients with ≥50% Reduction in Pain Score) at Endpoint Controlled PHN Studies Neurontin [package insert]. New York, New York: Pfizer Inc; 2009.
  35. 35. Conclusions • Irrespective of the neuropathic pain condition under treatment, the central pathways involved in these conditions remain the same; hence, the use of antidepressants and anticonvulsants that modulate pathways in patients with chronic pain will be very effective.
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