Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942008000500008
Brazilian Journal of Anesthesiology
Review Article

Dor neuropática: aspectos neuroquímicos

Neuropathic pain: neurochemical aspects

Durval Campos Kraychete; Judymara Lauzi Gozzani; Angiolina Campos Kraychete

Downloads: 0
Views: 1139

Resumo

JUSTIFICATIVA E OBJETIVOS: A dor neuropática é causada por lesão ou inflamação do sistema nervoso. É síndrome complexa, com mecanismos biológicos pouco esclarecidos, envolvendo teorias inflamatórias e imunes. O objetivo desta revisão foi descrever os principais fatores biológicos relacionados com a dor neuropática, associando de forma lógica as hipóteses sugeridas pela literatura. CONTEÚDO: Foram descritos os principais neuromediadores, canais iônicos e células, incluindo as do sistema imune envolvidos na excitabilidade neuronal, assim como enfatizada possível seqüência de ativação ou interação desses agentes na alteração neuroplástica decorrente da agressão ao nervo. CONCLUSÕES: Do estudo, foi possível concluir que os avanços no conhecimento da fisiopatologia da dor neuropática podem determinar novos alvos para abordagem farmacológica dessa síndrome.

Palavras-chave

DOR, FISIOLOGIA

Abstract

BACKGROUND AND OBJECTIVES: Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its biological mechanisms, involving inflammatory and immunologic theories, are not clear. The objective of this review was to describe the main biologic factors associated with neuropathic pain, making a logical association between hypotheses suggested in the literature. CONTENTS: The main neuromediators, ion channels, and cells, including cells in the nervous system involved in neuronal excitation are described, and the possible activation sequence or interaction among those agents in the neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS: It was possible to conclude that the advances on the knowledge of the pathophysiology of neuropathic pain can determine new pharmacologic approaches for this syndrome.

Keywords

PAIN, PHYSIOLOGY

References

Dworkin B and the Members of the Classification Subcommittee of the Special Interest Group of the International Association for the Study of Pain. .

Garcia-Larrea L, Magnin M. Physiopathologie de la douleur neuropathique: revue des modèles expérimentaux et des mécanismes proposés. Presse Med. 2008;37:315-340.

Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52:77-92.

Meyer RA, Ringkamp M, Campbell JN. Peripheral Mechanisms of Cutaneous Nociception. Wall and Melzack's: Textbook of Pain. 2006:3-34.

Ibrahim MM, Deng H, Zvonok A. Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci USA. 2003;100:10529-10533.

Gardell LR, Wang R, Ehrenfels C. Multiple actions of systemic artemin in experimental neuropathy. Nat Med. 2003;9:1383-1389.

Devor M. Response of Nerves to Injury in Relation to Neuropathic Pain. Wall and Melzack's: Textbook of Pain. 2006:905-927.

Sukhotinsky I, Ben Dor E, Raber P. Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur J Pain. 2004;8:135-143.

Schäfers M, Lee DH, Brors D. Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci. 2003;23:3028-3038.

Katsura H, Obata K, Mizushima T. Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol. 2006;200:112-123.

Rogers M, Tang L, Madge DJ. The role of sodium channels in neuropathic pain. Semin Cell Dev Biol. 2006;17:571-81.

Kohno T, Ji RR, Ito N. Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain. 2005;117:77-87.

Li CY, Song YH, Higuera ES. Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci. 2004;24:8494-8499.

Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429:23-37.

McLean PG, Ahluwalia A, Perretti M. Association between kinin B (1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules. J Exp Med. 2000;192:367- 380.

Baron R, Schwarz K, Kleinert A. Histamine-induced itch converts into pain in neuropathic hiperalgesia. Neuroreport. 2001;12:3475-78.

Mekori YA, Metcalfe DD. Mast cells in innate immunity. Immunol Rev. 2000;173:131-140.

Woolf CJ. Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. J Life Sci. 2004;74:2605- 2610.

Zuo Y, Perkins NM, Tracey DJ. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain. 2003;105:467-479.

Brück W. The role of macrophages in Wallerian degeneration. Brain Pathol. 1997;7:741-752.

Liu T, Van Rooijen N, Tracey DJ. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain. 2000;86:25-32.

Moalem G, Xu K, Yu L T. lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience. 2004;134:1399 -1411.

Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17:138-146.

Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hipersensitivity in a rat model neuropathy. J Pharmacol Exp Ther. 2003;306:624-630.

Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA. 2005;102:5856-5861.

Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24:450-455.

Spataro LE, Sloane EM, Milligan ED. Spinal gap junctions potential involvement in pain facilitation. Clin J Pain. 2004;5:392-405.

Bergsteinsdottir K, Kingston A, Jessen KR. Rat Schwann cells can be induced to express major histocompatibility complex class II molecules in vivo. J Neurocytol. 1992;21:382-390.

Liu GJ, Werry EL, Bennett MR. Secretion of ATP from Schwann cells in response to uridine triphosphate. Eur J Neurosci. 2005;21:151-160.

Skundric DS, Bealmear B, Lisak RP. Induced upregulation of IL-1, IL-1RA and IL-1R type I gene expression by Schwann cells. J Neuroimmunol. 1997;74:9-18.

Wang H, Kohno T, Amaya F. Bradykinin produces pain hupersensitivity by potentiating spinal cord glutamatergic synaptic transmission. J Neurosci. 2005;25:7986 -7992.

Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol. 2004;240:281-304.

Javis MF, Bugard EC, McGaraughty S. A-317491, a novel potent and selective non-nucleotide P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in rats. Proc Natl Acad Sci USA. 2002;99:17179-17184.

Tsuda M, Shigemoto-Mogami Y, Koizumi S. P2X4 receptors induced in spinal microglia gate tactile alodynia after nerve injury. Nature. 2003;424:778-783.

Chessell IP, Hatcher JP, Bountra C. Disruption of the P2X7 purinoreceptor gene4 abolishes chronic inflammatoty and neuropathic pain. Pain. 2005;114:386-96.

Xiao HS, Huang QH, Zhang FX. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci USA. 2002;99:8360-8365.

Hong Y, Abbott FV. Behavioural effects of intraplantar injection of inflammatory mediators in the rat. Neuroscience. 1994;63:827-836.

Moalem G, Grafe P, Tracey DJ. Chemical mediators enhance the excitability of unmyelinated sensory axons in normal and injured peripheral nerve of the rat. Neuroscience. 2005;134:1399-1411.

Taiwo YO, Levine JD. Prostaglandin effects after elimination of indirect hyperalgic mechanisms in the skin of the rat. Brain Res. 1989;492:397-399.

Malberg AB, Yaksh TL. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science. 1992;257:1276-1279.

Ma W, Einsenach JC. Morphological and pharmacological evidence of the role of peripheral prostaglandins in the pathogenesis of neuropathic pain. Eur J Neurosci. 2002;15:1037-1047.

Zhao Z, Chen SR, Eisenach JC. Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats. Neuroscience. 2000;97:743-748.

Ma W, Quirion R. Does COX2-dependent PGE2 play a role in neuropathic pain?. Neurosci Lett. 2008;437:165-169.

Levine JD, Lau W, Kwiat G. Leukotriene B4 produces hyperalgesia that is dependent on polymorphonuclear leukocytes. Science. 1984;225:743-745.

Bennett G, al-Rashed S, Hoult JR. Nerve growth factor induced hyperalgesia in the rat hind paw is dependent on circulating neutrophils. Pain. 1998;77:315-322.

Watikins LR, Hansen MK, Nguyen KT. Dynamic regulation of the pro-inflammatory cytokines, interleukin-1beta: molecular biology for non molecular biologists. Life Sci. 1999;65:449-481.

Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: Peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184-187.

Sung CS, Wen ZH, Chang WK. Intrathecal Interleukin-1beta administration induces thermal hiperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. Brain Res. 2004;1015:145-153.

Gillen C, Jander S, Stroll G. Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demylination and Wallerian degeneration. J Neurosci. 1998;51:489-496.

DeLeo JA, Yezierski RP. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain. 2001;90:1-6.

Oka T, Oka K, Hosoi M. Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats. Brain Res. 1995;692:123-128.

Murphy PG, Ramer MS, Borthwick L. Endogenous interleukin-6 contributes to hipersensitivity to cutaneous stimuli and changes in europeptides associated with chronic nerve constriction in mice. Eur J Neurosci. 1999;11:2243-2253.

Cunha FQ, Poole S, Lorenzetti BB. The pivotal role of tumor necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol. 1992;107:660-664.

Zelenka M, Shäfers M, Sommer C. Intraneural injection of interleukin-1beta and tumor necrois factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain. 2005;116:257-263.

Ignatowski TA, Covey WC, Knight PR. Brain-derived TNFalpha mediates neuropathic pain. Brain Res. 1999;841:70-77.

Moalem G, Gdalyahu A, Shani Y. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun. 2000;15:331-345.

Nykjaer A, Willnow TE, Petersen CM. P75(NTR).... Live or let die. Curr Opin Neurobiol. 2005;15:49-57.

Funakoshi H, Frisen J, Barbany G. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol. 1993;123:455-465.

Woolf CJ, Safieh-Garabedian B, Ma QP. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience. 1994;62:327-331.

Pezet S, Malcangio M, McMahon SB. BDNF: a neuromodulator in nociceptive pathways?. Brain Res Rev. 2002;40:240-249.

Miletic G, Miletic V. Increases in the concentration of brain derived neurotrophic factor in the lumbar spinal dorsal horn are associated with pain behavior following chronic constriction injury in rats. Neurosci Lett. 2002;319:137-140.

Aley KO, McCarter G, Levine JD. Nitric oxide signaling in pain and nociceptor sensitization in the rat. J Neurosci. 1998;18:7008-7014.

Levy D, Zochodne DW. No pain: potential roles of nitric oxide in neuropathic pain. Pain Pract. 2004;4:11-18.

Ueda H- Molecular mechanisms of neuropathic pain phenotypic switch and initiation mechanisms. Clin Pharmacol Ther. 2006;109:57-77.

Üçeler N, Sommer C. Wallerian degeneration and neuropathic pain. Drug Discov Today Dis Mech. 2006;3:351-356.

McMahon SB. Neuropathic Pain Mechanisms. Pain 2002: an updated review: Refresher course syllabuss. 2002:155-161.

Mannion RJ, Woolf CJ. Pain mechanisms and management: a central perspective. Clin J Pain. 2000;16:S144-156.

Rowbotham MC, Fields HL. The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain. 1996;119:347-354.

Choi B, Rowbotham MC. Effect of adrenergic receptor activation on post-herpetic neuralgia pain and sensory disturbances. Pain. 1997;69:55-63.

5dd6a4080e88257f2d13f28a rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections