@article{b240c612966b49a487b41c53d13f460e,
title = "Mechanisms of Neuropathic Pain",
abstract = "Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, {"}channelopathies,{"} and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. Neuropathic pain reflects both peripheral and central sensitization mechanisms. Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.",
author = "Campbell, {James N.} and Meyer, {Richard A.}",
note = "Funding Information: Nerve damage evokes a cascade of immune responses. Nerve damage leads to macrophage infiltration, T cell activation, and increased expression of proinflammatory cytokines. With axotomy, Schwann cells are in a sense denervated. These denervated Schwann cells (as well as cells in the partially denervated target tissue) may communicate with intact fibers that pass within the same nerve. This provides a mechanism by which to explain changes in the intact nociceptor (see above). Schwann cell denervation recruits macrophages via secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 (MCP-1) ( Sugiura et al., 2000 ). MCP-1 serves as a ligand for CCR2 ( Tofaris et al., 2002 ). CCR2 knockout mice do not develop mechanical hyperalgesia after a partial nerve ligation injury ( Abbadie et al., 2003 ). Cytokine IL-1β leads to increased expression of nerve growth factor (NGF), and NGF may sensitize nociceptors ( Kanaan et al., 1998 ). Knockout of the IL-1 receptor type I and genetically mediated overexpression of an IL-1 receptor antagonist decreased hyperalgesia. That the effect was peripheral was supported by the observation that spontaneous activity recorded from the dorsal root fibers was reduced ( Wolf et al., 2006 ). ",
year = "2006",
month = oct,
day = "5",
doi = "10.1016/j.neuron.2006.09.021",
language = "English (US)",
volume = "52",
pages = "77--92",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",
}