Highlights
- •Antihyperalgesic effect of resolvin D5 (RvD5) on trigeminal neuropathic pain in females and males.
- •RvD5 decreased IL-6 levels only in male rats.
- •RvD5 reduced acute nociceptive and inflammatory pain only in male rats.
Abstract
Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory
and analgesic properties. Orofacial pain conditions, especially those that are chronic,
present clinical challenges in terms of pharmacological management. Thus, new therapeutic
options are clearly warranted. Herein, we investigated the antinociceptive effect
of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model
and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5
at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced
by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects.
In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal
nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated
treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect
of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females.
Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced
facial grooming, in phases I and II of the test, but only in male rats. This study
demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models,
and corroborated previous evidence of sex dichotomy, with a greater effect in males.
This article presents a translational potential of RvD5 for targeted therapies aiming
at the control of acute and chronic trigeminal pain, but further studies are needed
to elucidate its sex-related mechanisms.
Perspective
This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic
pain treatment in male and female rats, but its effect on inflammatory orofacial pain
seems to be restricted only to males. Also, it provided the evidence for sex dichotomy
in the mechanisms related to the antinociceptive effect of RvD5.
Graphical Abstract
Graphical Abstract
Key words
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Article info
Publication history
Published online: December 27, 2022
Accepted:
December 22,
2022
Received in revised form:
December 6,
2022
Received:
July 5,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Research Funding: This work was supported by grants from the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil, finance code 001); Programa de Apoio a Grupos de Excelencia (PRONEX) grant supported by SETI/Araucaria Foundation and MCTI/CNPq; and Paraná State Government (agreement 014/2017, protocol 46.843). JGC is the recipient of a CNPq Productivity fellowship and RVL and DFB are recipients of PhD and MS respectively, scholarships from CAPES. E.I.A. is recipient of the International Headache Society (IHS) fellowship.
Conflict of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the results reported in this article.
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© 2022 by United States Association for the Study of Pain, Inc.
