High dose of QX-314 produces anti-nociceptive effect without capsaicin in rats with inflammatory TMJ pain

ABSTRACT

The present study investigated the effects of QX-314 on inflammatory pain of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, the TMJ of each animal was injected with 50 microL of formalin (5%). The number of noxious behavioral responses, including rubbing or scratching of the facial region including the TMJ area, was recorded over 9 sequential 5 min intervals for each animal. Although 2.5% QX-314 did not affect formalin-induced nociceptive behavior, administration of 5% QX-314 with formalin significantly decreased the number of scratches produced by the formalin injection. Co-administration of capsaicin, a TRPV1 agonist, with 2.5% QX-314 produced significant anti-nociceptive effects whereas 2.5% QX-314 alone did not. However, the co-administration of capsaicin did not enhance the anti-nociceptive effects in the 5% QX-314-treated rats. Moreover, the co-administration of capsazepine, a TRPV1 antagonist, did not attenuate anti-nociceptive effects in the 5% QX-314-treated rats. These findings suggest that TRPV1 is effective in the transport of low but not high doses of QX-314. Moreover, a high dose of QX-314, which is not mediated by peripheral TRPV1 activity, may be viable therapeutic strategy for inflammatory pain in the TMJ.