Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees


  • Niklas Schuelert,

    1. University of Calgary, Calgary, Alberta, Canada
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  • Jason J. McDougall

    Corresponding author
    1. University of Calgary, Calgary, Alberta, Canada
    • Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
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    • Dr. McDougall is an Alberta Heritage Foundation for Medical Research Senior Scholar and is recipient of an Arthritis Society of Canada Investigator award.



To determine whether local administration of the cannabinoid 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) can modulate joint nociception in control rat knee joints and in experimental osteoarthritis (OA).


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.


Local application of the CB1 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 CB1 receptor antagonist AM251 or the transient receptor potential vanilloid 1 (TRPV-1) ion channel antagonist SB366791 significantly reduced the desensitizing effect of ACEA. The CB1 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.


These findings indicate that activation of peripheral CB1 receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB1 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 CB1 receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB1 receptors may be important targets in controlling OA pain.