Abstract
Neuropathic pain may result from a wide spectrum of insults to the peripheral or central nervous system. This may include nutritional deficiencies, systemic diseases, chemotherapy, cerebrovascular accident, surgery or trauma. The hallmark of neuropathic pain is abnormal neural activity in peripheral nerve(s) or the central nervous system. This is often accompanied by disordered sensory processing both in the peripheral or central nervous system. Treating neuropathic pain is a major clinical challenge, and the underlying mechanisms of neuropathic pain remain elusive. The present review highlights pathophysiology of neuropathic pain and difficulty in treating the symptoms associated with it. This reflects our poor understanding of the pathophysiological processes which lead to neuropathic pain as well as the limited usefulness of many of our pharmacologic agents. An improved understanding of the pathophysiology of neuropathic pain as a result of laboratory research as well as novel means of delivering currently available drugs have provided us with an improved ability to treat certain types of neuropathic pain. Despite these advances, neuropathic pain remains extremely challenging to treat in the best of hands.
References
Ro LS, Chang KH (2005) Neuropathic pain: mechanisms and treatments. Chang. Gung. Med. J. 28: 597-605.
James N. Campbell, Allan I. Basaum, Andre Dray, Ronald Dubner, Robert H. Dworkin, Christine N (2006) Emerging Strategies for the Treatment of Neuropathic Pain. IASP Press.
Neuropathic pain (2010) The pharmacological management of neuropathic pain in adults in non-specialist settings; National Institute for Health and Care Excellence (NICE) Clinical Guidelines 96.
Dray A (2008) Neuropathic pain: emerging treatments. Br. J. Anaesth. 101(1): 48-58.
Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res. Rev. 51(2): 240- 264.
Marie Besson, Valérie Piguet, Pierre Dayer, Jules Desmeules (2008) New Approaches to the Pharmacotherapy of Neuropathic Pain. Expert Rev. Clin. Pharmacol. 1(5): 683- 693.
Dib-Hajj SD, Black JA, Waxman SG (2009) Voltage- gated sodium channels: therapeutic targets for pain. Pain Med. 10(7): 1260-1269.
Cummins TR, Dib-Hajj SD, Black JA, Waxman SG (2000) Sodium channels and the molecular pathophysiology of pain;. Prog. Brain Res. 129: 3-19.
Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR (2007) Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin. Genet. 71(4): 311-319.
Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al- Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature. 444(7121): 894-898.
Yu-Qing Cao (2006) Voltage-gated calcium channels and pain. Pain. 126: 5–9.
Snutch TP (2005) Targeting chronic and neuropathic pain: the N-type calcium channel comes of age. NeuroRx 2: 662–670.
Michael E, Hildebrand, Terrance P. Snutch (2006) Contributions of T-type calcium channels to the pathophysiology of pain signaling; Drug discovery today: disease mechanisms. 3(3): 335-341.
Mark HN (2012) Calcium Channel Blocker Treats Chronic Pain. Zalicus Inc., Cambridge, Mass.
Rosati M, Goedde T, Steffen F, Gandini G, De Risio L, Reese S, Matiasek K (2012) Developmental Changes in Voltage-Gated Calcium Channel α2δ-Subunit expression in the Canine Dorsal Root Ganglion. Dev. Neurosci. 34(5): 440– 448.
Ji RR, Xu ZZ, Wang X, Lo EH (2009) Matrix metalloprotease regulation of neuropathic pain. Trends Pharmacol. Sci. 30(7): 336-340.
Sommer C, Kress M (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci. Lett. 361: 184–187.
Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ, Samad TA (2008) Nociceptors are interleukin-1beta sensors. J. Neurosci. 28(52): 14062-14073.
Takacs E, Nyilas R, Szepesi Z, Baracskay P, Karlsen B, Rosvold T, Bjorkum AA, Czurko A, Kovacs Z, Kekesi AK, Juhasz G (2010) Matrix metalloproteinase-9 activity increased by two different types of epileptic seizures that do not induce neuronal death: a possible role in homeostatic synaptic plasticity. Neurochem. Int. 56(6-7): 799-809.
Wilczynski GM, Konopacki FA, Wilczek E, Lasiecka Z, Gorlewicz A, Michaluk P, Wawrzyniak M, Malinowska M, Okulski P, Kolodziej LR, Konopka W, Duniec K, Mioduszewska B, Nikolaev E, Walczak A, Owczarek D, Gorecki DC, Zuschratter W, Ottersen OP, Kaczmarek L (2008) Important role of matrix metalloproteinase 9 in epileptogenesis. J. Cell Biol. 180(5): 1021-1035.
Joachim Scholz, Clifford J Woolf (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat. Neurosci. 10(11): 1361–1368.
Sun XC, Chen WN, Li SQ, Cai JS, Li WB, Xian XH, Hu YY, Zhang M, Li QJ (2009) Fluorocitrate, an inhibitor of glial metabolism, inhibits the up-regulation of NOS expression, activity and NO production in the spinal cord induced by formalin test in rats. Neurochem. Res. 34(2): 351-359.
Tawfik VL, Nutile-McMenemy N, LaCroix-Fralish ML, DeLeo JA (2007) Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. Brain Behav. Immun. 21: 238–246.
Norsted Gregory E, Delaney A, Abdelmoaty S, Bas DB, Codeluppi S, Wigerblad G, Svensson CI (2013) Pentoxifylline and propentofylline prevent proliferation and activation of the mammalian target of rapamycin and mitogen activated protein kinase in cultured spinal astrocytes. J. Neurosci. Res. 91(2): 300-312.
Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR (2005) Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115(1-2): 71-83.
Zhang X, Xu Y, Wang J, Zhou Q, Pu S, Jiang W, Du D (2012) The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. J. Neural. Transm. 119(3): 329-336.
Sweitzer SM, DeLeo JA (2002) The active metabolite of leflunomide, an immunosuppressive agent, reduces mechanical sensitivity in a rat mononeuropathy model. J. Pain. 3: 360–368.
Si Q, Nakamura Y, Ogata T, Kataoka K, Schubert P (1998) Differential regulation of microglial activation by propentofylline via cAMP signaling. Brain Res. 812: 97–104.
Zemke D, Majid A (2004) The potential of minocycline for neuroprotection in human neurologic disease. Clin. Neuropharmacol. 27: 293–298.
McGaraughty S, Jarvis MF (2005) Antinociceptive properties of a non-nucleotide P2X3/P2X2/3 receptor antagonist. Drug News Perspect. 18: 501–507.
McGaraughty S, Chu KL, Namovic MT, Donnelly-Roberts DL, Harris RR, Zhang XF, Shieh CC, Wismer CT, Zhu CZ, Gauvin DM, Fabiyi AC, Honore P, Gregg RJ, Kort ME, Nelson DW, Carroll WA, Marsh K, Faltynek CR, Jarvis MF (2007) P2X7-related modulation of pathological nociception in rats. Neurosci. 146(4): 1817-1828.
Nephi Stella (2009) Endocannabinoid signaling in microglial cells. Neuropharmacol. 56: 244–253.
Ehrhart J, Obregon D, Mori T, Hou H, Sun N, Bai Y, Klein T, Fernandez F, Tan J, Shytle RD (2005) Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J. Neuroinflammation. 12: 29.
Umapathi T, Chaudhry V (2005) Toxic neuropathy. Curr. Opin. Neurol. 18(5): 574-580.
Svensson CI, Fitzsimmons B, Azizi S, Powell HC, Hua XY, Yaksh TL (2005) Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. J. Neurochem. 92(6): 1508-1520.
Schafers M, Svensson CI, Sommer C, Sorkin LS (2005) Tumor necrosis factor-α induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J. Neurosci. 23: 2517–2521.
Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther. 306: 624–630.
Tawfik VL, Nutile-McMenemy N, LaCroix-Fralish ML, DeLeo JA (2007) Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. Brain Behav. Immun. 21: 238–246.
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