当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Activation of NK₁ receptors in the locus coeruleus induces analgesia through noradrenergic-mediated descending inhibition in a rat model of neuropathic pain.

Activation of NK₁ receptors in the locus coeruleus induces analgesia through noradrenergic-mediated descending inhibition in a rat model of neuropathic pain.

Abstract：

BACKGROUND AND PURPOSE:The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykinin receptor, a functional receptor for SP. In the present study, we investigated the roles of SP in the LC in neuropathic pain. EXPERIMENTAL APPROACH:Chronic constriction injury (CCI) of the left sciatic nerve was performed in rats to induce neuropathic pain. After development of neuropathic pain, SP was injected into the LC and the nocifensive behaviours were assessed. The involvement of noradrenergic descending inhibition in SP-induced analgesia was examined by i.t. administration of yohimbine, an α(2) -adrenoceptor antagonist. NK(1) receptor expression in the LC was examined by immunohistochemistry. KEY RESULTS:In CCI rats, mechanical allodynia was alleviated by SP injection into the LC. These effects were abolished by prior injection of WIN 51708, an NK(1) receptor antagonist, into the LC or i.t. treatment with yohimbine. NK(1) receptor-like immunoreactivity was observed in noradrenergic neurons throughout the LC in intact rats, and remained unchanged after CCI. CONCLUSION AND IMPLICATIONS:SP in the LC exerted analgesic effects on neuropathic pain through NK(1) receptor activation and resulted in facilitation of spinal noradrenergic transmission. Accordingly, manipulation of the SP/NK(1) receptor signalling pathway in the LC may be a promising strategy for effective treatment of neuropathic pain.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Muto Y,Sakai A,Sakamoto A,Suzuki H

doi

10.1111/j.1476-5381.2011.01820.x

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1047-57

issue

3

eissn

0007-1188

issn

1476-5381

journal_volume

166

pub_type

杂志文章

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