神经病理性疼痛的分子机制.pdfVIP

Pharmacology Therapeutics 109 (2006) 57 – 77 /locate/pharmthera Associate editor: M. Endoh Molecular mechanisms of neuropathic pain–phenotypic switch and initiation mechanisms Hiroshi Ueda * Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan Abstract Many known painkillers are not always effective in the therapy of chronic neuropathic pain manifested by hyperalgesia and tactile allodynia. The mechanisms underlying neuropathic pain appear to be complicated and to differ from acute and inflammatory pain. Recent advances in pain research provide us with a clear picture for the molecular mechanisms of acute pain, and substantial information is available concerning the plasticity that occurs under conditions of neuropathic pain. The most important changes responsible for the mechanisms of neuropathic pain are found in the altered gene/protein expression in primary sensory neurons. After damage to peripheral sensory fibers, up- regulated expression of the Ca a y- channel subunit, the Na 1.3 sodium channel, and bradykinin (BK) B1 and capsaicin TRPV1 receptors in v 2 1 v myelinated neurons contribute to hyperalgesia; while the down-regulation of the Nav 1.8 sodium channel, B2 receptor, substance P (SP), and even A-opioid receptors in unmyelinated neurons is responsible for the phenotypic switch in pai