Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Author(s)

Abdalla, Henrique Ballassini ; Jain, Amit K. ; Napimoga, Marcelo Henrique ; Clemente-Napimoga, Juliana Trindade ; Gill, Harvinder Singh

• Document type: Journal article
• Source: Journal of Pharmacology and Experimental Therapeutics; v. 370, n. 3, p. 9-pg., 2019-09-01.

Abstract

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-alpha and interleukin-1 beta (IL-1 beta) 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. (AU)

• FAPESP's process: 17/22334-9 - Use of drug delivery systems for the development and application of anti-inflammatory agents with potential immunomodulatory and neuroprotective effects
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Research Projects - Thematic Grants