Abstract
Neuropathic pain is a chronic and pathological pain, occurring as a direct result of injury or disease affecting the somatosensory system. It is estimated to affect about 1.5% of world population and its therapeutic management is limited. There are important differences between peripheral nerve and central nervous system fibers, so its clinical manifestations and response to therapy may differ. The injury of peripheral nerve axons cause wallerian degeneration, but in other cases, retrograde degeneration, type “dying-back”. The main pathophysiological mechanisms that have been implicated in the genesis of neuropathic pain are functional plastic changes in nociceptive system, changes in the expression of voltage-dependent channels and neuroinflammatory responses mediated by the immune system.
Still more research is needed to provide a better quality of life for patients suffering from this crippling pain.
References
COSTIGAN M, SCHOLZ J, WOOLF CJ. Neuro- pathic Pain: A maladaptative response of the Ner- vous System to damage. Annu. Rev. Neurosci. 2009; 32:1–32.
BARON R, BINDER A, WASNER G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9: 807–819.
MERSKEY H, BOGDUK N. Classification of chronic pain, 2nd ed. Seattle, Wash: IASP Press; 1994: 394.
TREEDE RD, JENSEN TS, CAMPBELL JN, ET AL. Redefinition of neuropathic pain and a grading system for clinical use: consensus statement on clini- cal and research diagnostic criteria. Neurology 2008; 70:1630–1635.
GÓMEZ-BARRIOS JV, TORTORICI V. Mecanis- mos del dolor neuropático: del laboratorio a la clínica. Archivos Venezolanos de Farmacología y Terapéutica 2009; 28:2-11.
GRIFFIN JW, THOMPSON WJ. Biology and Pathology of Nonmyelinating Schwann Cells. Glia 2008; 56:1518-1531.
QUARLES RH, MACKLIN WB, MORELL P. Myelin Formation, Structure and Biochemistry. In: Siegel GJ, Albers RW, Brady ST, Price DL., eds. Basic Neurochemistry. 7th ed. Elsevier Academic Press; 2006:51-71.
KRISHNAN AV, LIN CSY, PARK SB, KIERNAN MC. Axonal ion channels from bench to bedside: A translational neuroscience perspective. Prog Neurobiol 2009; 89:288–313.
WAXMAN SG, CRANER MJ, BLACK JA. Na+ channel expression along axons in multiple sclerosis and its models. TIPS 2004; 25:584-591.
CHEN ZL, YUNG WM, STRICKLAND S. Periph- eral Regeneration. Annu. Rev. Neurosci. 2007; 30:209– 233.
SUNDERLAND S. The anatomy and physiology of nerve injury. Muscle Nerve 1990; 13:771–784.
BURNETT MG, ZAGER EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus 2004; 16:1-7.
WALLER A. Experiments on the Section of the Glossopharyngeal and Hypoglossal Nerves of the Frog, and Observations of the Alterations Pro- duced Thereby in the Structure of Their Primitive Fibres. Phil. Trans. R. Soc. Lond. 1850; 140, 423-429.
HUCHO T, LEVINE JD. Signaling pathways in sensitization: Toward a nociceptor cell biology. Neuron 2007; 55:365-376.
ORSTAVIC K, JØRUM E. Microneurographic findings of relevance to pain in patients with eryth- romelalgia and patients with diabetic neuropathy. Neurosci Lett 2010; 470:180-184.
NYSTROM B, HAGBARTH KE. Microelec- trode recordings from transected nerves in ampu- tees with phantom limb pain. Neurosci Lett 1981; 27:211–216.
JENSEN TS, FINNERUP NB. Neuropathic pain: Peripheral and central mechanisms. European Journal of Pain 2009;(Sup) 3: 33–36.
LATREMOLIERE A, WOOLF CJ. Central Sen- sitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity. J Pain 2009; 10:895-926.
WOOLF CJ, THOMPSON SW. The induction and maintenance of central sensitization is depen- dent on N-methyl-D-aspartic acid receptor activa- tion: Implications for the treatment of post-injury pain hypersensitivity states. Pain 1991; 44: 293-299.
MA QP, WOOLF CJ. Noxious stimuli induce an N-methyl-D-aspartate receptor-dependent hyper- sensitivity of the flexion withdrawal reflex to touch: Implications for the treatment of mechanical allo- dynia. Pain 1995; 61:383-390.
WOOLF CJ, SHORTLAND P, COGGESHALL RE. Peripheral nerve injury triggers central sprout- ing of myelinated afferent. Nature 1992; 355:75-78.
NAVARRO X, VIVÓ M, VALERO-CABRÉ A. Neural plasticity after peripheral nerve injury and regeneration. Progress in Neurobiology 2007; 82: 163–201.
SHEETS PL, HEERS C, STOEHR T, CUM- MINS TR. Differential block of sensory neuro- nal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypro- panamide], lidocaine, and carbamazepine. J. Phar- macol. Exp. Ther. 2008; 326:89–99.
CATTERALL, W.A., GOLDIN, A.L., WAXMAN,
S.G. International Union of Pharmacology. XLVII. nomenclature and structure–function relationships of voltage-gated sodium channels. Pharmacol. Rev. 2005; 57: 397–409..
KRAFTE DS, BANNON AW. Sodium channels and nociception: recent concepts and therapeutic opportunities. Curr Opin Pharmacol 2008; 8:50-56.
WAXMAN SG, KOCSIS JD, BLACK JA. Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reex- pressed following axotomy. J. Neurophysiol. 1994; 72:466-470.
DJOUHRI L, NEWTON R, LEVINSON SR, BERRY CM, CARRUTHERS B, LAWSON SN. Sen- sory and electrophysiological properties of guinea- pig sensory neurones expressing Nav1.7 (PN1) Na+ channel alpha-subunit protein. J. Physiol. 2003; 546:565–576.
CUMMINS TR,WAXMAN SG. Downregulation of tetrodotoxin-resistant sodium currents and upreg- ulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J. Neurosci. 1997; 17:3503–3514.
GOLD MS, WEINREICH D, KIM CS, WANG R, TREANOR J, ET AL. Redistribution of NaV1.8 in uninjured axons enables neuropathic pain. J. Neurosci. 2003; 23:158–6623:158–166.
ZHANG XF, ZHU CZ, THIMMAPAYA R, CHOI WS, HONORE P, ET AL. Differential action poten- tials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury. Brain Res. 2004; 1009:147–158.
FANG X, DJOUHRI L, MCMULLAN S, BERRY C, WAXMAN SG, ET AL. Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression. J. Neurosci. 2006; 26:7281–7292.
TATE S, BENN S, HICK C, TREZISE D, JOHN V, ET AL. Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons. Nat Neurosci 1998; 1:653–655.
WAN Y. Involvement of hyperpolarization- activated, cyclic nucleotide-gated cation channels in dorsal root ganglion in neuropathic pain. Acta Physi- ologica Sinica 2008; 60: 579-580.
SAAB CY, WAXMAN SG, HAINS BC. Alarm or curse? The pain of neuroinflammation. Brain Res Rev 2008; 58:226-235.
MYERS RR, CAMPANA WM, SHUVAYEV VI. The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets. DDT 2006; 11(1/2):8-20.
MARCHAND F, PERRETI M, MCMAHON SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005; 6:521-532.
GRAEBER MB. Changing Face of Microglia. Sci- ence 2010;330:783-788.
SALTER MW. Dorsal Horn Plasticity and Neuron- Microglia Interactions. In: Mogil JS, ed. Pain 2010-An Updated Review: Refresher Course Syllabus. Seattle: IASP Press; 2010:13-23.
TSUDA M, SHIGEMOTO-MOGAMI Y, KOI- ZUMI S, MIZOLOSHI A, KOHSAKA S, SALTER MW, INOUE K. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury Nature 2003; 424:778-783.
PRICE TJ, CERVERO F, GOLD MS, HAMMOND DL, PRESCOTT SA. Chloride regulation in the pain pathway. Brain Res Rev 2009; 60:149-170.
PITCHER MH, CERVERO F. Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons. Pain 2010; 151:756-762.
COULL JA, BEGGS S, BOUDREAU D, ET AL. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438:1017–1021.
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