Dataset Information

Central and peripheral sites of action for CB? receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats.

ABSTRACT:

Background and purpose

Cannabinoid CB? receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory and neuropathic pain. However, mechanisms underlying CB?-mediated analgesic effects remain largely unknown. The present study was conducted to elucidate the CB? receptor expression in 'pain relevant' tissues and the potential sites of action of CB? agonism in rats.

Experimental approach

Expression of cannabinoid receptor mRNA was evaluated by quantitative RT-PCR in dorsal root ganglia (DRGs), spinal cords, paws and several brain regions of sham, chronic inflammatory pain (CFA) and neuropathic pain (spinal nerve ligation, SNL) rats. The sites of CB? mediated antinociception were evaluated in vivo following intra-DRG, intrathecal (i.t.) or intraplantar (i.paw) administration of potent CB?-selective agonists A-836339 and AM1241.

Key results

CB? receptor gene expression was significantly up-regulated in DRGs (SNL and CFA), spinal cords (SNL) or paws (CFA) ipsilateral to injury under inflammatory and neuropathic pain conditions. Systemic A-836339 and AM1241 produced dose-dependent efficacy in both inflammatory and neuropathic pain models. Local administration of CB? agonists also produced significant analgesic effects in SNL (intra-DRG and i.t.) and CFA (intra-DRG) pain models. In contrast to A-836339, i.paw administration of AM-1241 dose-relatedly reversed the CFA-induced thermal hyperalgesia, suggesting that different mechanisms may be contributing to its in vivo properties.

Conclusions and implications

These results demonstrate that both DRG and spinal cord are important sites contributing to CB? receptor-mediated analgesia and that the changes in CB? receptor expression play a crucial role for the sites of action in regulating pain perception.

SUBMITTER: Hsieh GC

PROVIDER: S-EPMC3031063 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats.

Hsieh Gin C GC Pai Madhavi M Chandran Prasant P Hooker Bradley A BA Zhu Chang Z CZ Salyers Anita K AK Wensink Erica J EJ Zhan CenChen C Carroll William A WA Dart Michael J MJ Yao Betty B BB Honore Prisca P Meyer Michael D MD

British journal of pharmacology 20110101 2

<h4>Background and purpose</h4>Cannabinoid CB₂ receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory and neuropathic pain. However, mechanisms underlying CB₂-mediated analgesic effects remain largely unknown. The present study was conducted to elucidate the CB₂ receptor expression in 'pain relevant' tissues and the potential sites of action of CB₂ agonism in rats.<h4>Experimental approach</h4>Expression of cannabinoid receptor ...[more]

PMID: 20880025

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