Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy  

作　　者：Jie Yu Guo-Dong Lou Jia-Xing Yue Ying-Ying Tang Wei-Wei Hou Wen-Ting Shou Hiroshi Ohtsu Shi-Hong Zhang Zhong Chen 

机构地区：[1]Department of Pharmacology, School of Basic Medical Sciences [2]College of Pharmaceutical Sciences, Zhejiang University [3]School of Pharmaceutical Sciences, Wenzhou Medical College [4]Department of Engineering, School of Medicine, Tohoku University

出　　处：《Neuroscience Bulletin》2013年第3期261-269,共9页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (81030061, 30701015, 81173042);partly by the Foundation for Science and Technology Innovation Team, Zhejiang Province, China (2011R50014)

摘　　要：The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain （NP） induced by peripheral axotomy. Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP （the neuroma model）. Rats were then treated with drugs once daily for 30 days （histidine and Ioratadine, i.p.） or 21 days （histamine, i.c.v.）. Autotomy behavior was scored daily until day 50 postoperation （PO）. On days 14 to 21 PO, some rats in the control group were subjected to singlefiber recording. Autotomy behavior was also monitored daily in histidine decarboxylase （the key enzyme for histamine synthesis） knockout （HDC/） and wildtype mice for 42 days. We found that both histidine （500 mg/kg） （a precursor of histamine that increases histamine levels in the tissues） and histamine （50 pg/5 pL） significantly suppressed autotomy behavior in rats. HDC mice lacking endogenous histamine showed higher levels of autotomy than the wildtype. In addition, the analgesic effect of histidine was not antagonized by Ioratadine （a peripherallyacting H1 receptor antago nist）, while Ioratadine alone significantly suppressed autotomy. Electrophysiological recording showed that ectopic spontaneous discharges from the neuromawere blocked by systemic diphenhydramine （an H receptor antagonist）. Our results suggest that hista mine plays an important role in spontaneous NP. It is likely that histamine in the central nervous system is analgesic, while in the periphery, via H receptors, it is algesic. This study justifies the avoidance of a histaminerich diet and the use of peripherallyacting H receptor antagonists as well as agents that improve histamine action in the central nervous system in pa tients with spontaneous NP.The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain （NP） induced by peripheral axotomy. Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP （the neuroma model）. Rats were then treated with drugs once daily for 30 days （histidine and Ioratadine, i.p.） or 21 days （histamine, i.c.v.）. Autotomy behavior was scored daily until day 50 postoperation （PO）. On days 14 to 21 PO, some rats in the control group were subjected to singlefiber recording. Autotomy behavior was also monitored daily in histidine decarboxylase （the key enzyme for histamine synthesis） knockout （HDC/） and wildtype mice for 42 days. We found that both histidine （500 mg/kg） （a precursor of histamine that increases histamine levels in the tissues） and histamine （50 pg/5 pL） significantly suppressed autotomy behavior in rats. HDC mice lacking endogenous histamine showed higher levels of autotomy than the wildtype. In addition, the analgesic effect of histidine was not antagonized by Ioratadine （a peripherallyacting H1 receptor antago nist）, while Ioratadine alone significantly suppressed autotomy. Electrophysiological recording showed that ectopic spontaneous discharges from the neuromawere blocked by systemic diphenhydramine （an H receptor antagonist）. Our results suggest that hista mine plays an important role in spontaneous NP. It is likely that histamine in the central nervous system is analgesic, while in the periphery, via H receptors, it is algesic. This study justifies the avoidance of a histaminerich diet and the use of peripherallyacting H receptor antagonists as well as agents that improve histamine action in the central nervous system in pa tients with spontaneous NP.

关 键 词：HISTAMINE Ioratadine H1 receptor neuropathic pain 

分 类 号：R651.1[医药卫生—外科学]