Small-conductance calcium-activated potassium SK channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis painReport as inadecuate




Small-conductance calcium-activated potassium SK channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 11:51

First Online: 28 August 2015Received: 22 May 2015Accepted: 21 August 2015

Abstract

BackgroundArthritis pain is an important healthcare issue with significant emotional and affective consequences. Here we focus on potentially beneficial effects of activating small-conductance calcium-activated potassium SK channels in the amygdala, a brain center of emotions that plays an important role in central pain modulation and processing. SK channels have been reported to regulate neuronal activity in the central amygdala CeA, output nucleus. We tested the effects of riluzole, a clinically available drug for the treatment of amyotrophic lateral sclerosis, for the following reasons. Actions of riluzole include activation of SK channels. Evidence in the literature suggests that riluzole may have antinociceptive effects through an action in the brain but not the spinal cord. Mechanism and site of action of riluzole remain to be determined. Here we tested the hypothesis that riluzole inhibits pain behaviors by acting on SK channels in the CeA in an arthritis pain model.

ResultsSystemic intraperitoneal application of riluzole 8 mg-kg inhibited audible nocifensive response and ultrasonic averse affective response vocalizations of adult rats with arthritis 5 h postinduction of a kaolin-carrageenan monoarthritis in the knee but did not affect spinal withdrawal thresholds, which is consistent with a supraspinal action. Stereotaxic administration of riluzole into the CeA by microdialysis 1 mM, concentration in the microdialysis fiber, 15 min also inhibited vocalizations, confirming the CeA as a site of action of riluzole. Stereotaxic administration of a selective SK channel blocker apamin, 1 µM, concentration in the microdialysis fiber, 15 min into the CeA had no effect by itself but inhibited the effect of systemic riluzole on vocalizations. Off-site administration of apamin into the basolateral amygdala BLA as a placement control or stereotaxic application of a selective blocker of large-conductance calcium-activated potassium BK channels charybdotoxin, 1 µM, concentration in the microdialysis fiber, 15 min into the CeA did not affect the inhibitory effects of systemically applied riluzole.

ConclusionsThe results suggest that riluzole can inhibit supraspinally organized pain behaviors in an arthritis model by activating SK, but not BK, channels in the amygdala CeA but not BLA.

KeywordsAmygdala Pain Behavior Vocalizations Riluzole Potassium channels SK channels BK channels Microdialysis AbbreviationsACSFartificial cerebrospinal fluid

AHPafterhyperpolarization

ALSamyotrophic lateral sclerosis

BK channellarge-conductance calcium-activated potassium channel

BLAbasolateral nucleus of the amygdala

CeAcentral nucleus of the amygdala

ChTxcharybdotoxin

HBC2-hydroxypropyl-β-cyclodextrin

i.p.intraperitoneal

LAlateral nucleus of the amygdala

SK channelsmall-conductance calcium-activated potassium channel

Download fulltext PDF



Author: Jeremy M. Thompson - Guangchen Ji - Volker Neugebauer

Source: https://link.springer.com/







Related documents