Soluble epoxide hydrolase inhibition avoid formalin-induced inflammatory hyperalgesia in the temporomandibular joint

Author(s)

Abdalla, Henrique Ballassini ; Napimoga, Marcelo Henrique ; Teixeira, Juliana Maia ; Trindade-da-Silva, Carlos Antonio ; Pieroni, Victor Luis ; dos Santos Araujo, Fernanda Souto Maior ; Hammock, Bruce D. ; Clemente-Napimoga, Juliana Trindade

• Document type: Journal article
• Source: INFLAMMOPHARMACOLOGY; v. 30, n. 3, p. 10-pg., 2022-03-18.

Abstract

Epoxyeicosatrienoic acids (EETs) are endogenous molecules that exerts effective antinociceptive and resolutive actions. However, because of their rapid metabolism by the soluble epoxide hydrolase (sEH), EETs are unable to remain bioavailable. Therefore, the aim of this study was to investigate whether local sEH inhibition could prevent inflammatory hyperalgesia in the temporomandibular joint (TMJ) of rats. For that, rats were pre-treated with an intra-TMJ injection of TPPU, followed by the noxious stimulus (1.5% of formalin intra-articular) to evaluate nociceptive behavior. Histological analysis was conducted to explore the inflammatory exudate and mast cell degranulation. Periarticular tissue over the TMJ was used to measure inflammatory lipids and cytokines/chemokine by Enzyme-Linked Immunosorbent Assay (ELISA). We demonstrated that peripheral pretreatment with TPPU prevents formalin-induced inflammatory hyperalgesia in the TMJ, and this effect is strictly local. Moreover, TPPU mitigates the leukocyte exudate in the TMJ, as well as inflammatory lipids mediators. Mast cell number and degranulation were abrogated by TPPU, and the inflammatory cytokine levels were decreased by TPPU. On the other hand, TPPU up-regulated the release of interleukin 10 (IL-10), an anti-inflammatory cytokine. We provide evidence that locally sEH by intra-TMJ injection of TPPU produces an antinociceptive and anti-inflammatory effect on rats' TMJ. (AU)

• FAPESP's process: 18/05575-5 - Evaluation of the peripheral antinociceptive effect of the soluble epoxy hydrolase inhibitor, TPPU, on formalin-induced hypernociception in the temporomandibular joint of rats
• Grantee: Victor Luís Pieroni
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• 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