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Activation of peripheral cannabinoid receptors attenuates cutaneous hyperalgesia produced by a heat injury.
Pain 2004; 109(3):432-42PAIN

Abstract

Accumulating evidence suggests that cannabinoids can produce antinociception through peripheral mechanisms. In the present study, we determined whether cannabinoids attenuated existing hyperalgesia produced by a mild heat injury to the glabrous hindpaw and whether the antihyperalgesia was receptor-mediated. Anesthetized rats received a mild heat injury (55 degrees C for 30 s) to one hindpaw. Fifteen minutes after injury, animals exhibited hyperalgesia as evidenced by lowered withdrawal latency to radiant heat and increased withdrawal frequency to a von Frey monofilament (200 mN force) delivered to the injured hindpaw. Separate groups of animals were then treated with an intraplantar (i.pl.) injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2 at doses of 1, 10, or 30 microg in 100 microl. WIN 55,212-2 attenuated both heat and mechanical hyperalgesia dose-dependently. The inactive enantiomer WIN 55,212-3 did not alter mechanical or heat hyperalgesia, suggesting the effects of WIN 55,212-2 were receptor-mediated. The CB1 receptor antagonist AM 251 (30 microg) co-injected with WIN 55,212-2 (30 microg) attenuated the antihyperalgesic effects of WIN 55,212-2. The CB2 receptor antagonist AM 630 (30 microg) co-injected with WIN 55,212-2 attenuated only the early antihyperalgesic effects of WIN 55,212-2. I.pl. injection of WIN 55,212-2 into the contralateral paw did not alter the heat-injury induced hyperalgesia, suggesting that the antihyperalgesia occurred through a peripheral mechanism. These data demonstrate that cannabinoids primarily activate peripheral CB1 receptors to attenuate hyperalgesia. Activation of this receptor in the periphery may attenuate pain without causing unwanted side effects mediated by central CB1 receptors.

Authors+Show Affiliations

Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15157704

Citation

Johanek, Lisa M., and Donald A. Simone. "Activation of Peripheral Cannabinoid Receptors Attenuates Cutaneous Hyperalgesia Produced By a Heat Injury." Pain, vol. 109, no. 3, 2004, pp. 432-42.
Johanek LM, Simone DA. Activation of peripheral cannabinoid receptors attenuates cutaneous hyperalgesia produced by a heat injury. Pain. 2004;109(3):432-42.
Johanek, L. M., & Simone, D. A. (2004). Activation of peripheral cannabinoid receptors attenuates cutaneous hyperalgesia produced by a heat injury. Pain, 109(3), pp. 432-42.
Johanek LM, Simone DA. Activation of Peripheral Cannabinoid Receptors Attenuates Cutaneous Hyperalgesia Produced By a Heat Injury. Pain. 2004;109(3):432-42. PubMed PMID: 15157704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of peripheral cannabinoid receptors attenuates cutaneous hyperalgesia produced by a heat injury. AU - Johanek,Lisa M, AU - Simone,Donald A, PY - 2003/09/02/received PY - 2004/02/06/revised PY - 2004/02/23/accepted PY - 2004/5/26/pubmed PY - 2004/10/1/medline PY - 2004/5/26/entrez SP - 432 EP - 42 JF - Pain JO - Pain VL - 109 IS - 3 N2 - Accumulating evidence suggests that cannabinoids can produce antinociception through peripheral mechanisms. In the present study, we determined whether cannabinoids attenuated existing hyperalgesia produced by a mild heat injury to the glabrous hindpaw and whether the antihyperalgesia was receptor-mediated. Anesthetized rats received a mild heat injury (55 degrees C for 30 s) to one hindpaw. Fifteen minutes after injury, animals exhibited hyperalgesia as evidenced by lowered withdrawal latency to radiant heat and increased withdrawal frequency to a von Frey monofilament (200 mN force) delivered to the injured hindpaw. Separate groups of animals were then treated with an intraplantar (i.pl.) injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2 at doses of 1, 10, or 30 microg in 100 microl. WIN 55,212-2 attenuated both heat and mechanical hyperalgesia dose-dependently. The inactive enantiomer WIN 55,212-3 did not alter mechanical or heat hyperalgesia, suggesting the effects of WIN 55,212-2 were receptor-mediated. The CB1 receptor antagonist AM 251 (30 microg) co-injected with WIN 55,212-2 (30 microg) attenuated the antihyperalgesic effects of WIN 55,212-2. The CB2 receptor antagonist AM 630 (30 microg) co-injected with WIN 55,212-2 attenuated only the early antihyperalgesic effects of WIN 55,212-2. I.pl. injection of WIN 55,212-2 into the contralateral paw did not alter the heat-injury induced hyperalgesia, suggesting that the antihyperalgesia occurred through a peripheral mechanism. These data demonstrate that cannabinoids primarily activate peripheral CB1 receptors to attenuate hyperalgesia. Activation of this receptor in the periphery may attenuate pain without causing unwanted side effects mediated by central CB1 receptors. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/15157704/Activation_of_peripheral_cannabinoid_receptors_attenuates_cutaneous_hyperalgesia_produced_by_a_heat_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304395904001009 DB - PRIME DP - Unbound Medicine ER -