期刊
NEUROPHARMACOLOGY
卷 61, 期 4, 页码 825-831出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2011.05.030
关键词
alpha-Adrenoceptor; Biting; Descending noradrenergic system; Itch; Spinal cord
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan [22790063]
- Health, Labour and Welfare Ministry, Japan
- Grants-in-Aid for Scientific Research [22790063] Funding Source: KAKEN
It has recently been shown that clonidine suppresses itch-related responses via its action on alpha(2)-adrenoceptors in the spinal cord, raising the possibility that the descending noradrenergic system regulates itch signaling in the spinal cord. In this study, we investigated whether the transmission of itch signals in the spinal cord is under tonic inhibition by the descending noradrenergic system. An intraplantar injection of serotonin in mice induced biting of the treated paw (an itch-related response). An intrathecal injection of 6-hydroxydopamine (catecholaminergic neurotoxin) enhanced the itch-related response. There was a significant inverse correlation between the response and noradrenaline content. An intrathecal injection of phentolamine (alpha-adrenoceptor antagonist) enhanced serotonin-induced biting, although prazosin (alpha(1)-, alpha(2B)-, and alpha(2C)-adrenoceptor antagonist) and yohimbine (alpha(2)-adrenoceptor antagonist) had no effects. Intrathecal injections of phenylephrine (alpha(1)-adrenoceptor agonist) and clonidine (alpha(2)-adrenoceptor agonist) inhibited serotonin-induced biting. The action of phenylephrine was antagonized by intrathecal prazosin but not 5-methylurapidil (alpha(1A)-adrenoceptor antagonist), cyclazosin (alpha(1B)-adrenoceptor antagonist), and EMY 7378 (alpha(1D)-adrenoceptor antagonist). mRNAs encoding alpha(1A)-, alpha(1B)-, alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenoceptor subtypes were expressed in the dorsal root ganglion and spinal dorsal horn. These results suggest that the descending noradrenergic system exerts tonic inhibition on itch signaling in the spinal cord. Both alpha(1)- and alpha(2)-adrenoceptors may be involved in the tonic inhibition of itch signaling and the stimulation of either alpha-adrenoceptor subtype may result in the inhibition of itch. (C) 2011 Elsevier Ltd. All rights reserved.
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