TY - JOUR T1 - Microneedles coated with tramadol exhibit anti-nociceptive effect in a rat model of temporomandibular hypernociception JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.256750 SP - jpet.119.256750 AU - Henrique Ballassini Abdalla AU - Amit K Jain AU - Marcelo Henrique Napimoga AU - Juliana Trindade Clemente-Napimoga AU - Harvinder Singh Gill Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/early/2019/03/14/jpet.119.256750.abstract N2 - Coated microneedles have emerged as a promising drug delivery system for inflammatory pain treatment. We have previously shown that tramadol injection in to the rat temporomandibular joint (TMJ) induces an antinociceptive and an anti-inflammatory effect. In this study, microneedles coated with tramadol were investigated as a painless platform to treat TMJ pain. Male Wistar rats were administered tramadol using an intra TMJ injection or with microneedles coated with tramadol, followed by 1.5% formalin nociceptive challenge administered 15 minutes later. The nociceptive behavior of rats was evaluated, and their periarticular tissues were removed after euthanasia for analysis. The duration of antinociceptive effect was determined by performing the formalin challenge at different time points extending up to six days post tramadol administration. Microneedles coated with tramadol produced an antinociceptive effect similar to injection of tramadol in to the rat TMJ. Surprisingly, tramadol delivery using coated microneedles produced a more durable antinociceptive effect lasting as much as two days post tramadol delivery as compared to an antinociceptive effect lasting under two hours from intra TMJ injection of tramadol. The pro-inflammatory cytokines TNF-α and IL-1β were found to be reduced while the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups. In conclusion, microneedles coated with tramadol can offer a painless and an easy-to-use therapeutic option for pain-control of inflammatory disorders in the TMJ. ER -