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

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 $50{\mu}L$ 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.

이상의 실험 결과들을 요약하면, 포르말린을 측두하악관절 내로 주입하여 발생한 염증성 통증 행위반응은 QX-314의 투여로 감소할 수 있었다. 저농도의 QX-314의 진통작용은 TRPV1 통로를 이용하여 세포막 내로 이동하여 작용이 나타났으며 고농도의 QX-314는 TRPV1 통로와 무관하게 진통작용을 나타내었다. 이와 같은 결과는 측두하악관절 장애로 인해 발생되는 염증성 통증에 QX-314가 효과적인 치료제로 사용할 수 있다는 것을 말해주며, 특히 고농도의 QX-314가 세포막을 이동하는 경로에 대한 연구가 더 진행된다면 임상에서 QX-314가 진통제로서 사용할 수 있는 계기가 될 것으로 판단된다.