PT  - JOURNAL ARTICLE
AU  - Henrique Ballassini Abdalla
AU  - Amit K. Jain
AU  - Marcelo Henrique Napimoga
AU  - Juliana Trindade Clemente-Napimoga
AU  - Harvinder Singh Gill
TI  - Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception
AID  - 10.1124/jpet.119.256750
DP  - 2019 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 834--842
VI  - 370
IP  - 3
4099  - http://jpet.aspetjournals.org/content/370/3/834.short
4100  - http://jpet.aspetjournals.org/content/370/3/834.full
SO  - J Pharmacol Exp Ther2019 Sep 01; 370
AB  - Coated microneedles have emerged as a promising drug delivery system for inflammatory pain treatment. We have previously shown that tramadol injection into the rat temporomandibular joint (TMJ) induces an antinociceptive and anti-inflammatory effect. In this study, microneedles coated with tramadol were investigated as a 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 6 days post tramadol administration. Microneedles coated with tramadol produced an antinociceptive effect similar to injection of tramadol into the rat TMJ. Surprisingly, tramadol delivery using coated microneedles produced a more durable antinociceptive effect lasting as much as 2 days post tramadol delivery as compared with an antinociceptive effect lasting under 2 hours from intra-TMJ injection of tramadol. The proinflammatory cytokines tumor necrosis factor-α and interleukin-1β (IL-1β) were found to be reduced, whereas the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups. In conclusion, microneedles coated with tramadol can offer a therapeutic option for pain control of inflammatory disorders in the TMJ.