title: Effect of memantine on the levels of neuropeptides and microglial cells in the brain regions of rats with neuropathic pain.
abstract: Neuropathic pain induced by sciatic nerve injury not only causes peripheral dysfunctions but also affects the cortical and subcortical regions of the brain. It is still unknown whether neuropathic pain could relate to behavioral and neurochemical alterations in the central nervous system. This paper deals with the effect of peripheral neuropathic pain on mechanical allodynia, neuropeptide levels, neuropeptide-degrading enzyme activities, and microglial cells in the brain regions of rats by applying chronic constriction injury, a partial sciatic nerve injury. We examined the possible protection effect on the allodynia and changes in levels of neuropeptides and microglial activation in chronic constriction injury of the rat brain by memantine. On 4 days after chronic constriction injury, the induction of mechanical allodynia was suppressed by memantine treatment. Reductions in the substance P in the hypothalamus and somatostatin in the periaqueductal gray of chronic constriction injury rat brain were reversed by memantine. This suggests the role of these neuropeptides in pain information processing in the brain. Immunohistochemical experiments revealed that the expression of CD11b, a marker protein of microglia, was increased in the hypothalamus and periaqueductal gray in the chronic constriction injury rat brain as compared with the controls, and memantine treatment could suppress the activation of microglia, suggesting the involvement of microglia in pain mechanism. The present behavioral, biochemical, and immunohistochemical studies demonstrated that peripheral neuropathic pain affects the neuropeptide levels and microglial activation in the brain regions, and these events described above may play an important role in neuropathic pain pathogenesis.
authors: Department of Research and Development, Abbott Diagnostic Division, Minato, Tokyo 106-8535, Japan.
authors: Katsumichi
authors: K
authors: Takeda
authors: Mai
authors: M
authors: Muramatsu
authors: Toshiyuki
authors: T
authors: Chikuma
authors: Takeshi
authors: T
authors: Kato
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018845:CD11 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009479:Neuropeptides / Q000187:drug effects* / Q000378:metabolism; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
chemical_list: D000700:Analgesics; D018845:CD11 Antigens; D018691:Excitatory Amino Acid Antagonists; D009479:Neuropeptides; D013373:Substance P; D013004:Somatostatin; D008559:Memantine