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Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats.
Br J Pharmacol 2011; 162(2):428-40BJ

Abstract

BACKGROUND AND PURPOSE

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.

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 CB₂ mediated antinociception were evaluated in vivo following intra-DRG, intrathecal (i.t.) or intraplantar (i.paw) administration of potent CB₂-selective agonists A-836339 and AM1241.

KEY RESULTS

CB₂ 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 CB₂ 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 CB₂ receptor-mediated analgesia and that the changes in CB₂ receptor expression play a crucial role for the sites of action in regulating pain perception.

Authors+Show Affiliations

Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, IL 60064, USA. gin.c.hsieh@abbott.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20880025

Citation

Hsieh, Gin C., et al. "Central and Peripheral Sites of Action for CB₂ Receptor Mediated Analgesic Activity in Chronic Inflammatory and Neuropathic Pain Models in Rats." British Journal of Pharmacology, vol. 162, no. 2, 2011, pp. 428-40.
Hsieh GC, Pai M, Chandran P, et al. Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. Br J Pharmacol. 2011;162(2):428-40.
Hsieh, G. C., Pai, M., Chandran, P., Hooker, B. A., Zhu, C. Z., Salyers, A. K., ... Meyer, M. D. (2011). Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. British Journal of Pharmacology, 162(2), pp. 428-40. doi:10.1111/j.1476-5381.2010.01046.x.
Hsieh GC, et al. Central and Peripheral Sites of Action for CB₂ Receptor Mediated Analgesic Activity in Chronic Inflammatory and Neuropathic Pain Models in Rats. Br J Pharmacol. 2011;162(2):428-40. PubMed PMID: 20880025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. AU - Hsieh,Gin C, AU - Pai,Madhavi, AU - Chandran,Prasant, AU - Hooker,Bradley A, AU - Zhu,Chang Z, AU - Salyers,Anita K, AU - Wensink,Erica J, AU - Zhan,CenChen, AU - Carroll,William A, AU - Dart,Michael J, AU - Yao,Betty B, AU - Honore,Prisca, AU - Meyer,Michael D, PY - 2010/10/1/entrez PY - 2010/10/1/pubmed PY - 2011/6/30/medline SP - 428 EP - 40 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 162 IS - 2 N2 - BACKGROUND AND PURPOSE: 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. 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 CB₂ mediated antinociception were evaluated in vivo following intra-DRG, intrathecal (i.t.) or intraplantar (i.paw) administration of potent CB₂-selective agonists A-836339 and AM1241. KEY RESULTS: CB₂ 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 CB₂ 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 CB₂ receptor-mediated analgesia and that the changes in CB₂ receptor expression play a crucial role for the sites of action in regulating pain perception. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/20880025/Central_and_peripheral_sites_of_action_for_CB₂_receptor_mediated_analgesic_activity_in_chronic_inflammatory_and_neuropathic_pain_models_in_rats_ L2 - https://doi.org/10.1111/j.1476-5381.2010.01046.x DB - PRIME DP - Unbound Medicine ER -