Cannabinoid‐mediated antinociception is enhanced in rat osteoarthritic knees
Tóm tắt
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 CB1agonist 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;
These findings indicate that activation of peripheral CB1receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB1receptor 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 CB1receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB1receptors may be important targets in controlling OA pain.
Từ khóa
Tài liệu tham khảo
Kalbhen DA, 1987, Chemical model of osteoarthritis: a pharmacological evaluation, J Rheumatol, 14
Schaible HG, 1983, Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint, J Neurophysiol, 49, 35, 10.1152/jn.1983.49.1.35
Rice AS, 2001, Cannabinoids and pain, Curr Opin Investig Drugs, 2, 399
Mackie K, 1993, Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells, Mol Pharmacol, 44, 498
Howlett AC, 1988, Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model, Mol Pharmacol, 33, 297
Szallasi A, 1999, Vanilloid (capsaicin) receptors and mechanisms, Pharmacol Rev, 51, 159, 10.1016/S0031-6997(24)01403-0
Hillard CJ, 1999, Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1), J Pharmacol Exp Ther, 289, 1427, 10.1016/S0022-3565(24)38289-8