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neuropathic pain

Pain that results from a disturbance of function or pathologic change in a nerve; in one nerve mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse & bilateral, polyneuropathy. Etiology: neuropathic pain syndromes 1) peripheral nervous system a) postherpetic neuralgia b) trigeminal neuralgia c) painful diabetic polyneuropathy d) trauma/surgery/post-amputation (phantom limb pain) e) common in patients with peripheral neuropathy [9] - diabetic neuropathy f) HIV1 infection 2) central nervous system a) post-stroke pain (central pain) b) myelopathic/radiculopathic pain 1] multiple sclerosis 2] spinal stenosis 3] arachnoiditis 4] root sleeve fibrosis 3) sympathetic nervous system a) reflex sympathetic dystrophy b) causalgia (complex regional pain syndromes) c) lumbosacral plexopathy Pathology: 1) spontaneous & paroxysmal discharges of pain fibers a) injury to peripheral nerves b) nociceptive receptors become highly sensitive to mechanical stimulation 2) loss of central inhibitory modulation - spinal pain afferents may become spontaneously active if cut off from their normal input 3) interaction of sympathetic nervous system with somatic afferent nociceptive receptors 4) primary afferents may develop sensitivity to norepinephrine 5) Na+ channel alpha subunit SCN10A may play a role Clinical manifestations: 1) pain is referred to body region innervated by damaged nerves 2) sensory deficit is generally present in the area of the patient's pain 3) qualities a) tingling b) burning c) shooting d) stabbing (lancinating) e) paroxysmal f) vice-like g) electric-shock like 4) paresthesias 5) pain may be triggered by light touch 6) pain is often severe & refractory to conventional pain management 7) typically affects distal extremities 8) often worse at night [9] Special laboratory: - lidocaine test Complications: - increased risk of suicide (hazzard ratio = 1.4) Differential diagnosis: - spinal stenosis manifects during activity (not worse at night) Management: analgesia 1) topical capsaicin or lidocaine patch or cream 2) from Japanese Society of Pain Clinicians a) pregabalin, gabapentin, duloxetine & SNRI 1st line [12] b) tramadol 2nd line [12] c) opiates 3rd line [12] 3) tricyclic antidepressants, gabapentenoids, carbamazepine & SNRI 1st line (MKSAP19) [9] 4) antidepressants a) low dose tricyclic antidepressant (TCA) (first line) [9] - amitriptyline, nortriptyline - TCA most effective at treating paresthesias, burning, dysethesias b) duloxetine, venlafaxine (first line, moderate-certainty evidence) [9,13] - duloxetine is first line in management of chemotherapy-induced neuropathic pain [14] c) bupropion (sustained-release) 150-300 mg QD [3] d) amitriptyline only TCA with strong evidence supporting use [10] - low-certainty evidence of benefit [13] e) SNRIs useful for treatment of depression with comorbid pain syndromes - SNRI more effective than SSRI for depression with neuropathic pain 5) anticonvulsants a) valproic acid b) gabapentin, pregabalin - not as effective as tricyclic antidepressant [9] c) topiramate [5] d) carbamazepine effective but risk of SIADH e) phenytoin f) lamotrigine g) oxcarbazine h) tiagabine i) zonisamide j) levetiracetam 6) combination of nortriptyline + gabapentin more effective than either agent alone [7] 7) opiates (oral or parenteral) - not first choice for neuropathic pain [11] - avoid use for chronic neuropathic pain (risk of addiction) [9] 8) mexiletine 9) clonazepam [5] 10) lidocaine infusion when opiates are not effective 11) botulinum toxin A injections may be effective [6]

Specific

neuralgia

General

chronic pain chronic neurologic disease

References

  1. Pain Management, The American Medical Association, Overview of Physiology, Assessment & Treatment, 2003
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 55
  3. Journal Watch 22(1):10, 2002 Semenchunk et al, Neurology 57:1583, 2001
  4. Harden RN, Houle TT, Remble TA, Lin W, Wang K, Saltz S. Topiramate for phantom limb pain: a time-series analysis. Pain Med. 2005 Sep-Oct;6(5):375-8. PMID: 16266358
  5. UpToDate 13.3 http://www.utdol.com
  6. Yuan RY et al. Botulinum toxin for diabetic neuropathic pain: A randomized double-blind crossover trial. Neurology 2009 Apr 28; 72:1473. PMID: 19246421
  7. Gilron I et al, Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial Lancet 2009 Oct 10; 374:1252. PMID: 19796802 doi:10.1016/S0140-6736(09)61081-3 http://www.thelancet.com/journals/lanonc/article/PIIS0140-6736(09)61081-3/fulltext - Jensen TS and Finnerup NB Neuropathic pain treatment: a further step forward The Lancet, 30 September 2009 PMID: 19796803 doi:10.1016/S0140-6736(09)61205-8 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61205-8/fulltext
  8. Veterans Administration Memorandum Dec 24, 2009 Recent VHA Findings regarding chronic pain conditions and suicide risk
  9. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  10. Wong J, Motulsky A, Abrahamowicz M et al. Off-label indications for antidepressants in primary care: Descriptive study of prescriptions from an indication based electronic prescribing system. BMJ 2017;356:j603 PMID: 28228380 Free PMC Article http://www.bmj.com/content/356/bmj.j603
  11. American Association of Neuromuscular & Electrodiagnostic Medicine Ten Things Physicians and Patients Should Question Choosing Wisely. February 10, 2015 (1-5), July 31, 2017 (6-10) http://www.choosingwisely.org/societies/american-association-of-neuromuscular-electrodiagnostic-medicine/
  12. Sumitani M, Sakai T, Matsuda Y, et al. Executive summary of the Clinical Guidelines of Pharmacotherapy for Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians. J Anesth. 2018 Jun;32(3):463-478. PMID: 29737410 Free PMC Article https://link.springer.com/article/10.1007%2Fs00540-018-2501-0
  13. Ferreira GE et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: Overview of systematic reviews. BMJ 2023 Feb 1; 380:e072415. PMID: 36725015 PMCID: PMC9887507 Free PMC article https://www.bmj.com/content/380/bmj-2022-072415 - Stannard C, Wilkinson C. Rethinking use of medicines for chronic pain. BMJ 2023 Feb 1; 380:170. PMID: 36724987 https://www.bmj.com/content/380/bmj.p170
  14. Smith EM et al Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy. A Randomized Clinical Trial. JAMA. 2013;309(13):1359-1367 PMID: 23549581 http://jama.jamanetwork.com/article.aspx?articleid=1674238