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Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees.
Arthritis Rheum. 2008 Jan; 58(1):145-53.AR

Abstract

OBJECTIVE

To determine whether local administration of the cannabinoid 1 (CB(1)) receptor agonist arachidonyl-2-chloroethylamide (ACEA) can modulate joint nociception in control rat knee joints and in experimental osteoarthritis (OA).

METHODS

OA was induced in male Wistar rats by intraarticular injection of 3 mg of sodium mono-iodoacetate, with a recovery period of 14 days. Electrophysiologic recordings were made of knee joint primary afferent nerve fibers in response to normal rotation and noxious hyperrotation of the joint both before and after close intraarterial injection of different doses of ACEA.

RESULTS

Local application of the CB(1) agonist significantly reduced the firing rate of afferent nerve fibers by up to 50% in control knee joints (n=19) and up to 62% in OA knee joints (n=29; P<0.01). Coadministration of the CB(1) receptor antagonist AM251 or the transient receptor potential vanilloid 1 (TRPV-1) ion channel antagonist SB366791 significantly reduced the desensitizing effect of ACEA. The CB(1) receptor antagonist AM251 by itself had no effect in the control joint but significantly increased the firing rate of afferent nerve fibers in the OA joint.

CONCLUSION

These findings indicate that activation of peripheral CB(1) receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB(1) receptor or the TRPV-1 channel significantly reduced the efficacy of ACEA, which suggests that both receptors are involved in cannabinoid-mediated antinociception. The increased nerve activity observed following CB(1) receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB(1) receptors may be important targets in controlling OA pain.

Authors+Show Affiliations

University of Calgary, Calgary, Alberta, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18163511

Citation

Schuelert, Niklas, and Jason J. McDougall. "Cannabinoid-mediated Antinociception Is Enhanced in Rat Osteoarthritic Knees." Arthritis and Rheumatism, vol. 58, no. 1, 2008, pp. 145-53.
Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008;58(1):145-53.
Schuelert, N., & McDougall, J. J. (2008). Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis and Rheumatism, 58(1), 145-53. https://doi.org/10.1002/art.23156
Schuelert N, McDougall JJ. Cannabinoid-mediated Antinociception Is Enhanced in Rat Osteoarthritic Knees. Arthritis Rheum. 2008;58(1):145-53. PubMed PMID: 18163511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. AU - Schuelert,Niklas, AU - McDougall,Jason J, PY - 2008/1/1/pubmed PY - 2008/3/11/medline PY - 2008/1/1/entrez SP - 145 EP - 53 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 58 IS - 1 N2 - OBJECTIVE: To determine whether local administration of the cannabinoid 1 (CB(1)) receptor agonist arachidonyl-2-chloroethylamide (ACEA) can modulate joint nociception in control rat knee joints and in experimental osteoarthritis (OA). METHODS: OA was induced in male Wistar rats by intraarticular injection of 3 mg of sodium mono-iodoacetate, with a recovery period of 14 days. Electrophysiologic recordings were made of knee joint primary afferent nerve fibers in response to normal rotation and noxious hyperrotation of the joint both before and after close intraarterial injection of different doses of ACEA. RESULTS: Local application of the CB(1) agonist significantly reduced the firing rate of afferent nerve fibers by up to 50% in control knee joints (n=19) and up to 62% in OA knee joints (n=29; P<0.01). Coadministration of the CB(1) receptor antagonist AM251 or the transient receptor potential vanilloid 1 (TRPV-1) ion channel antagonist SB366791 significantly reduced the desensitizing effect of ACEA. The CB(1) receptor antagonist AM251 by itself had no effect in the control joint but significantly increased the firing rate of afferent nerve fibers in the OA joint. CONCLUSION: These findings indicate that activation of peripheral CB(1) receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB(1) receptor or the TRPV-1 channel significantly reduced the efficacy of ACEA, which suggests that both receptors are involved in cannabinoid-mediated antinociception. The increased nerve activity observed following CB(1) receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB(1) receptors may be important targets in controlling OA pain. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/18163511/Cannabinoid_mediated_antinociception_is_enhanced_in_rat_osteoarthritic_knees_ L2 - https://doi.org/10.1002/art.23156 DB - PRIME DP - Unbound Medicine ER -