Brief research report: Repurposing pentoxifylline to treat intense acute swimming-Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms

Sergio M Borghi; Tiago H Zaninelli; Telma Saraiva-Santos; Mariana M Bertozzi; Renato D R Cardoso; Thacyana T Carvalho; Camila R Ferraz; Doumit Camilios-Neto; Fernando Q Cunha; Thiago M Cunha; Felipe A Pinho-Ribeiro; Rubia Casagrande; Waldiceu A Verri Jr

doi:10.3389/fphar.2022.950314

Brief research report: Repurposing pentoxifylline to treat intense acute swimming-Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms

Front Pharmacol. 2023 Jan 10:13:950314. doi: 10.3389/fphar.2022.950314. eCollection 2022.

Affiliations

¹ Department of Pathology, Center of Biological Sciences, State University of Londrina, Londrina, Brazil.
² Center for Research in Health Science, University of Northern Paraná, Londrina, Brazil.
³ Department of Biochemistry and Biotechnology, Exact Sciences Center, State University of Londrina, Londrina, Brazil.
⁴ Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
⁵ Department of Pharmaceutical Sciences, Center of Health Sciences, State University of Londrina, Londrina, Brazil.

Abstract

In this study, we pursue determining the effect of pentoxifylline (Ptx) in delayed-onset muscle soreness (DOMS) triggered by exposing untrained mice to intense acute swimming exercise (120 min), which, to our knowledge, has not been investigated. Ptx treatment (1.5, 4.5, and 13.5 mg/kg; i.p., 30 min before and 12 h after the session) reduced intense acute swimming-induced mechanical hyperalgesia in a dose-dependent manner. The selected dose of Ptx (4.5 mg/kg) inhibited recruitment of neutrophils to the muscle tissue, oxidative stress, and both pro- and anti-inflammatory cytokine production in the soleus muscle and spinal cord. Furthermore, Ptx treatment also reduced spinal cord glial cell activation. In conclusion, Ptx reduces pain by targeting peripheral and spinal cord mechanisms of DOMS.

Keywords: cytokine; glial cells; muscle mechanical hyperalgesia; oxidative stress; pentoxifylline.

Grants and funding

This work was supported under Brazilian grants from CAPES (finance code 001), CNPq (#309633/2021-4; #307852/2019-9; #405027/2021-4; #427946/2018-2; #307689/2022-0), FAPESP (#2013/08216-2; Center for Research in Inflammatory Disease), PRONEX grant supported by Araucária Foundation, SETI, MCTI, CNPq, and Paraná State Government (#014/2017).