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Annual Review of Pharmacology and Toxicology

Volume 60, 2020

Neuropathic Pain: Mechanism-Based Therapeutics

Abstract

Neuropathic pain (NeP) can result from sources as varied as nerve compression, channelopathies, autoimmune disease, and incision. By identifying the neurobiological changes that underlie the pain state, it will be clinically possible to exploit mechanism-based therapeutics for maximum analgesic effect as diagnostic accuracy is optimized. Obtaining sufficient knowledge regarding the neuroadaptive alterations that occur in a particular NeP state will result in improved patient analgesia and a mechanism-based, as opposed to a disease-based, therapeutic approach to facilitate target identification. This will rely on comprehensive disease pathology insight; our knowledge is vastly improving due to continued forward and back translational preclinical and clinical research efforts. Here we discuss the clinical aspects of neuropathy and currently used drugs whose mechanisms of action are outlined alongside their clinical use. Finally, we consider sensory phenotypes, patient clusters, and predicting the efficacy of an analgesic for neuropathy.

Keyword(s): clinical targets, neurobiology, neuropathic pain, neuropathy, patient clusters, sensory phenotypes
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2020-01-06
2024-04-25
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Literature Cited

  1. 1. 
    Attal N, Lanteri-Minet M, Laurent B, Fermanian J, Bouhassira D 2011. The specific disease burden of neuropathic pain: results of a French nationwide survey. Pain 152:122836–43
     [Google Scholar]
  2. 2. 
    Torrance N, Ferguson JA, Afolabi E, Bennett MI, Serpell MG et al. 2013. Neuropathic pain in the community: more under-treated than refractory?. Pain 154:5690–99
     [Google Scholar]
  3. 3. 
    Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B et al. 2005. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114:1–229–36
     [Google Scholar]
  4. 4. 
    Torrance N, Smith BH, Bennett MI, Lee AJ 2006. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J. Pain 7:4281–89
     [Google Scholar]
  5. 5. 
    Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C 2008. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 136:3380–87
     [Google Scholar]
  6. 6. 
    Dieleman JP, Kerklaan J, Huygen FJ, Bouma PA, Sturkenboom MC 2008. Incidence rates and treatment of neuropathic pain conditions in the general population. Pain 137:3681–88
     [Google Scholar]
  7. 7. 
    Zorina-Lichtenwalter K, Parisien M, Diatchenko L 2018. Genetic studies of human neuropathic pain conditions: a review. Pain 159:3583–94
     [Google Scholar]
  8. 8. 
    Haythornthwaite JA, Clark MR, Pappagallo M, Raja SN 2003. Pain coping strategies play a role in the persistence of pain in post-herpetic neuralgia. Pain 106:3453–60
     [Google Scholar]
  9. 9. 
    Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH et al. 2017. Neuropathic pain. Nat. Rev. Dis. Primers 3:17002
     [Google Scholar]
  10. 10. 
    Kim SH, Chung JM. 1992. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:3355–63
     [Google Scholar]
  11. 11. 
    Seltzer Z, Dubner R, Shir Y 1990. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:2205–18
     [Google Scholar]
  12. 12. 
    Ahlgren SC, Levine JD. 1993. Mechanical hyperalgesia in streptozotocin-diabetic rats. Neuroscience 52:41049–55
     [Google Scholar]
  13. 13. 
    Decosterd I, Woolf CJ. 2000. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:2149–58
     [Google Scholar]
  14. 14. 
    Bennett GJ, Xie YK. 1988. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:187–107
     [Google Scholar]
  15. 15. 
    Yezierski RP, Liu S, Ruenes GL, Kajander KJ, Brewer KL 1998. Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain 75:1141–55
     [Google Scholar]
  16. 16. 
    King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G et al. 2009. Unmasking the tonic-aversive state in neuropathic pain. Nat. Neurosci. 12:111364–66
     [Google Scholar]
  17. 17. 
    Kocsis JD, Waxman SG. 1987. Ionic channel organization of normal and regenerating mammalian axons. Prog. Brain Res. 71:89–101
     [Google Scholar]
  18. 18. 
    Devor M. 2006. Sodium channels and mechanisms of neuropathic pain. J. Pain 7:Suppl. 1S3–12
     [Google Scholar]
  19. 19. 
    Tsantoulas C, McMahon SB. 2014. Opening paths to novel analgesics: the role of potassium channels in chronic pain. Trends Neurosci 37:3146–58
     [Google Scholar]
  20. 20. 
    Patel R, Dickenson AH. 2016. Mechanisms of the gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain. Pharmacol. Res. Perspect. 4:2e00205
     [Google Scholar]
  21. 21. 
    Suzuki R, Matthews EA, Dickenson AH 2001. Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy. Pain 91:1–2101–9
     [Google Scholar]
  22. 22. 
    Dickenson AH, Patel R. 2018. Sense and sensibility—logical approaches to profiling in animal models. Pain 159:71426–28
     [Google Scholar]
  23. 23. 
    Doyon N, Ferrini F, Gagnon M, De Koninck Y 2013. Treating pathological pain: Is KCC2 the key to the gate?. Expert Rev. Neurother. 13:5469–71
     [Google Scholar]
  24. 24. 
    Zhang ZJ, Jiang BC, Gao YJ 2017. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain. Cell Mol. Life Sci. 74:183275–91
     [Google Scholar]
  25. 25. 
    Navratilova E, Ji G, Phelps C, Qu C, Hein M et al. 2018. Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain. Pain 160:4824–32
     [Google Scholar]
  26. 26. 
    Bee LA, Dickenson AH. 2007. Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states. Neuroscience 147:3786–93
     [Google Scholar]
  27. 27. 
    Bannister K, Dickenson AH. 2016. What the brain tells the spinal cord. Pain 157:102148–51
     [Google Scholar]
  28. 28. 
    Ossipov MH, Morimura K, Porreca F 2014. Descending pain modulation and chronification of pain. Curr. Opin. Support Palliat. Care 8:2143–51
     [Google Scholar]
  29. 29. 
    De Felice M, Sanoja R, Wang R, Vera-Portocarrero L, Oyarzo J et al. 2011. Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain. Pain 152:122701–9
     [Google Scholar]
  30. 30. 
    Bannister K, Patel R, Goncalves L, Townson L, Dickenson AH 2015. Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations. Pain 156:91803–11
     [Google Scholar]
  31. 31. 
    Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y 2012. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain 153:61193–98
     [Google Scholar]
  32. 32. 
    Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A 2014. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br. J. Anaesth. 113:1148–56
     [Google Scholar]
  33. 33. 
    Wagner R, DeLeo JA, Coombs DW, Willenbring S, Fromm C 1993. Spinal dynorphin immunoreactivity increases bilaterally in a neuropathic pain model. Brain Res 629:2323–26
     [Google Scholar]
  34. 34. 
    Vanderah TW, Gardell LR, Burgess SE, Ibrahim M, Dogrul A et al. 2000. Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. J. Neurosci. 20:7074–79
     [Google Scholar]
  35. 35. 
    Draisci G, Kajander KC, Dubner R, Bennett GJ, Iadarola MJ 1991. Up-regulation of opioid gene expression in spinal cord evoked by experimental nerve injuries and inflammation. Brain Res 560:1–2186–92
     [Google Scholar]
  36. 36. 
    Wang Z, Gardell LR, Ossipov MH, Vanderah TW, Brennan MB et al. 2001. Pronociceptive actions of dynorphin maintain chronic neuropathic pain. J. Neurosci. 21:51779–86
     [Google Scholar]
  37. 37. 
    Vanderah TW, Laughlin T, Lashbrook JM, Nichols ML, Wilcox GL et al. 1996. Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone. Pain 68:275–81
     [Google Scholar]
  38. 38. 
    Choi JS, Hudmon A, Waxman SG, Dib-Hajj SD 2006. Calmodulin regulates current density and frequency-dependent inhibition of sodium channel Nav1.8 in DRG neurons. J. Neurophysiol. 96:197–108
     [Google Scholar]
  39. 39. 
    Mao J, Sung B, Ji RR, Lim G 2002. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J. Neurosci. 22:8312–23
     [Google Scholar]
  40. 40. 
    Amir R, Kocsis JD, Devor M 2005. Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons. J. Neurosci. 25:102576–85
     [Google Scholar]
  41. 41. 
    Mao J, Price DD, Mayer DJ 1994. Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C. J. Neurosci. 14:42301–12
     [Google Scholar]
  42. 42. 
    Trujillo KA, Akil H. 1991. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:498985–87
     [Google Scholar]
  43. 43. 
    Zhang HM, Chen SR, Pan HL 2009. Effects of activation of group III metabotropic glutamate receptors on spinal synaptic transmission in a rat model of neuropathic pain. Neuroscience 158:2875–84
     [Google Scholar]
  44. 44. 
    Bennett AD, Everhart AW, Hulsebosch CE 2000. Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury. Brain Res 859:172–82
     [Google Scholar]
  45. 45. 
    Ultenius C, Linderoth B, Meyerson BA, Wallin J 2006. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat. Neurosci. Lett. 399:1–285–90
     [Google Scholar]
  46. 46. 
    Iwata H, Takasusuki T, Yamaguchi S, Hori Y 2007. NMDA receptor 2B subunit-mediated synaptic transmission in the superficial dorsal horn of peripheral nerve-injured neuropathic mice. Brain Res 1135:192–101
     [Google Scholar]
  47. 47. 
    Urban MO, Gebhart GF. 1999. Supraspinal contributions to hyperalgesia. PNAS 96:147687–92
     [Google Scholar]
  48. 48. 
    Zhang W, Gardell S, Zhang D, Xie JY, Agnes RS et al. 2009. Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors. Brain 132:3778–87
     [Google Scholar]
  49. 49. 
    Suzuki R, Porreca F, Dickenson AH 2006. Evidence for spinal dorsal horn hyperexcitability in rats following sustained morphine exposure. Neurosci. Lett. 407:156–61
     [Google Scholar]
  50. 50. 
    Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TP Jr et al. 2001. Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the μ-opioid receptor. J. Neurosci. 21:145281–88
     [Google Scholar]
  51. 51. 
    Burgess SE, Gardell LR, Ossipov MH, Malan TP Jr, Vanderah TW et al. 2002. Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J. Neurosci. 22:125129–36
     [Google Scholar]
  52. 52. 
    Bennett GJ, Chung JM, Honore M, Seltzer Z 2003. Models of neuropathic pain in the rat. Curr. Protoc. Pharmacol. 22:9.14
     [Google Scholar]
  53. 53. 
    Hains BC, Waxman SG. 2007. Sodium channel expression and the molecular pathophysiology of pain after SCI. Prog. Brain Res. 161:195–203
     [Google Scholar]
  54. 54. 
    Bostock H, Campero M, Serra J, Ochoa JL 2005. Temperature-dependent double spikes in C-nociceptors of neuropathic pain patients. Brain 128:92154–63
     [Google Scholar]
  55. 55. 
    Nassar MA, Baker MD, Levato A, Ingram R, Mallucci G et al. 2006. Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice. Mol. Pain 2:33
     [Google Scholar]
  56. 56. 
    Gold MS, Weinreich D, Kim CS, Wang R, Treanor J et al. 2003. Redistribution of NaV1.8 in uninjured axons enables neuropathic pain. J. Neurosci. 23:1158–66
     [Google Scholar]
  57. 57. 
    Joshi SK, Mikusa JP, Hernandez G, Baker S, Shieh CC et al. 2006. Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states. Pain 123:1–275–82
     [Google Scholar]
  58. 58. 
    Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S et al. 2007. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. PNAS 104:208520–25
     [Google Scholar]
  59. 59. 
    Dib-Hajj SD, Yang Y, Black JA, Waxman SG 2013. The NaV1.7 sodium channel: from molecule to man. Nat. Rev. Neurosci. 14:149–62
     [Google Scholar]
  60. 60. 
    Minett MS, Nassar MA, Clark AK, Passmore G, Dickenson AH et al. 2012. Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nat. Commun. 3:791
     [Google Scholar]
  61. 61. 
    Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K et al. 2008. Pharmacological disruption of calcium channel trafficking by the α2δ ligand gabapentin. PNAS 105:93628–33
     [Google Scholar]
  62. 62. 
    Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y et al. 2001. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J 20:102349–56
     [Google Scholar]
  63. 63. 
    Woolf CJ, Salter MW. 2000. Neuronal plasticity: increasing the gain in pain. Science 288:54721765–69
     [Google Scholar]
  64. 64. 
    LaBuda CJ, Koblish M, Little PJ 2005. Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain. Eur. J. Pharmacol. 527:1–3172–74
     [Google Scholar]
  65. 65. 
    Moss A, Beggs S, Vega-Avelaira D, Costigan M, Hathway GJ et al. 2007. Spinal microglia and neuropathic pain in young rats. Pain 128:3215–24
     [Google Scholar]
  66. 66. 
    Perkins FM, Kehlet H. 2000. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology 93:41123–33
     [Google Scholar]
  67. 67. 
    Chizh BA, Göhring M, Tröster A, Quartey GK, Schmelz M, Koppert W 2007. Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br. J. Anaesth. 98:2246–54
     [Google Scholar]
  68. 68. 
    Bannister K, Qu C, Navratilova E, Oyarzo J, Xie JY et al. 2017. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain. Pain 158:122386–95
     [Google Scholar]
  69. 69. 
    Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L et al. 1997. The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur. J. Pharmacol. 324:2–3153–60
     [Google Scholar]
  70. 70. 
    Field MJ, Cox PJ, Stott E, Melrose H, Offord J et al. 2006. Identification of the α2-δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. PNAS 103:4617537–42
     [Google Scholar]
  71. 71. 
    Bauer CS, Nieto-Rostro M, Rahman W, Tran-Van-Minh A, Ferron L et al. 2009. The increased trafficking of the calcium channel subunit α2δ-1 to presynaptic terminals in neuropathic pain is inhibited by the α2δ ligand pregabalin. J. Neurosci. 29:134076–88
     [Google Scholar]
  72. 72. 
    Patel R, Bauer CS, Nieto-Rostro M, Margas W, Ferron L et al. 2013. α2δ-1 gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage. J. Neurosci. 33:4216412–26
     [Google Scholar]
  73. 73. 
    Juarez-Salinas DL, Braz JM, Hamel KA, Basbaum AI 2018. Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls. Pain Rep 3:4e659
     [Google Scholar]
  74. 74. 
    Chiechio S, Copani A, Melchiorri D, Canudas AM, Storto M et al. 2004. Metabotropic receptors as targets for drugs of potential use in the treatment of neuropathic pain. J. Endocrinol. Investig. 27:Suppl. 6171–76
     [Google Scholar]
  75. 75. 
    Eide K, Stubhaug A, Oye I, Breivik H 1995. Continuous subcutaneous administration of the N-methyl-d-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia. Pain 61:2221–28
     [Google Scholar]
  76. 76. 
    Jevtovic-Todorovic V, Wozniak DF, Powell S, Nardi A, Olney JW 1998. Clonidine potentiates the neuropathic pain-relieving action of MK-801 while preventing its neurotoxic and hyperactivity side effects. Brain Res 781:1–2202–11
     [Google Scholar]
  77. 77. 
    Osikowicz M, Mika J, Przewlocka B 2013. The glutamatergic system as a target for neuropathic pain relief. Exp. Physiol. 98:2372–84
     [Google Scholar]
  78. 78. 
    Vučković S, Srebro D, Vujović KS, Vučetić Č, Prostran M 2018. Cannabinoids and pain: new insights from old molecules. Front. Pharmacol. 9:1259
     [Google Scholar]
  79. 79. 
    Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W 2018. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst. Rev. 3:CD012182
     [Google Scholar]
  80. 80. 
    Kim DW, Lee SK, Ahnn J 2015. Botulinum toxin as a pain killer: players and actions in antinociception. Toxins 7:72435–53
     [Google Scholar]
  81. 81. 
    Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ et al. 2016. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol 15:6555–65
     [Google Scholar]
  82. 82. 
    Yong YL, Tan LT, Ming LC, Chan KG, Lee LH et al. 2016. The effectiveness and safety of topical capsaicin in postherpetic neuralgia: a systematic review and meta-analysis. Front. Pharmacol. 7:538
     [Google Scholar]
  83. 83. 
    Burness CB, McCormack PL. 2016. Capsaicin 8% patch: a review in peripheral neuropathic pain. Drugs 76:1123–34
     [Google Scholar]
  84. 84. 
    Baron R, Maier C, Attal N, Binder A, Bouhassira D et al. 2017. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain 158:2261–72
     [Google Scholar]
  85. 85. 
    Rolke R, Baron R, Maier C, Tölle TR, Treede RD et al. 2006. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 123:3231–43
     [Google Scholar]
  86. 86. 
    Vollert J, Magerl W, Baron R, Binder A, Enax-Krumova EK et al. 2018. Pathophysiological mechanisms of neuropathic pain: comparison of sensory phenotypes in patients and human surrogate pain models. Pain 159:61090–102
     [Google Scholar]
  87. 87. 
    Vollert J, Maier C, Attal N, Bennett DLH, Bouhassira D et al. 2017. Stratifying patients with peripheral neuropathic pain based on sensory profiles: algorithm and sample size recommendations. Pain 158:81446–55
     [Google Scholar]
  88. 88. 
    Bouhassira D, Attal N. 2016. Translational neuropathic pain research: a clinical perspective. Neuroscience 338:27–35
     [Google Scholar]
  89. 89. 
    Mainka T, Malewicz NM, Baron R, Enax-Krumova EK, Treede RD, Maier C 2016. Presence of hyperalgesia predicts analgesic efficacy of topically applied capsaicin 8% in patients with peripheral neuropathic pain. Eur. J. Pain 20:1116–29
     [Google Scholar]
  90. 90. 
    Westermann A, Krumova EK, Pennekamp W, Horch C, Baron R, Maier C 2012. Different underlying pain mechanisms despite identical pain characteristics: a case report of a patient with spinal cord injury. Pain 153:71537–40
     [Google Scholar]
  91. 91. 
    Demant DT, Lund K, Vollert J, Maier C, Segerdahl M et al. 2014. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain 155:112263–73
     [Google Scholar]
  92. 92. 
    Simpson DM, Schifitto G, Clifford DB, Murphy TK, Durso-De Cruz E et al. 2010. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology 74:5413–20
     [Google Scholar]
  93. 93. 
    Patel R, Kucharczyk M, Montagut-Bordas C, Lockwood S, Dickenson AH 2019. Neuropathy following spinal nerve injury shares features with the irritable nociceptor phenotype: a back-translational study of oxcarbazepine. Eur. J. Pain 23:1183–97
     [Google Scholar]
  94. 94. 
    Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD 2019. The role of voltage-gated sodium channels in pain signaling. Physiol. Rev. 99:21079–151
     [Google Scholar]
  95. 95. 
    Lindskou TA, Christensen SW, Graven-Nielsen T 2017. Cuff algometry for estimation of hyperalgesia and pain summation. Pain Med 18:3468–76
     [Google Scholar]
  96. 96. 
    Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R et al. 2015. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14:2162–73
     [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010818-021524
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Neuropathic Pain: Mechanism-Based Therapeutics
Annual Review of Pharmacology and Toxicology 60, 257 (2020); https://doi.org/10.1146/annurev-pharmtox-010818-021524
/content/journals/10.1146/annurev-pharmtox-010818-021524
/content/journals/10.1146/annurev-pharmtox-010818-021524
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