High-intensity swimming exercise reduces neuropathic pain in an animal model of complex regional pain syndrome type I: Evidence for a role of the adenosinergic system

Abstract

This study investigated the involvement of the adenosinergic system in antiallodynia induced by exercise in an animal model of complex regional pain syndrome type I (CRPS-I). Furthermore, we analyzed the role of the opioid receptors on exercise-induced analgesia. Ischemia/reperfusion (IR) mice, nonexercised and exercised, received intraperitoneal injections of caffeine (10mg/kg, a non selective adenosine receptor antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (0.1mg/kg, a selective adenosine A1 receptor antagonist), ZM241385 (3mg/kg, a selective adenosine A2A receptor antagonist), adenosine deaminase inhibitor erythro-9-(2-hydroxy-3nonyl) adenine [(EHNA), 5mg/kg, an adenosine deaminase inhibitor] or naloxone (1mg/kg, a nonselective opioid receptor antagonist). The results showed that high-intensity swimming exercise reduced mechanical allodynia in an animal model of CRPS-I in mice. The antiallodynic effect caused by exercise was reversed by pretreatment with caffeine, naloxone, DPCPX but it was not modified by ZM241385 treatment. In addition, treatment with EHNA, which suppresses the breakdown of adenosine to inosine, enhanced the pain-relieving effects of the high-intensity swimming exercise. This is the first report demonstrating that repeated sessions of high-intensity swimming exercise attenuate mechanical allodynia in an animal model of CRPS-I and that the mechanism involves endogenous adenosine and adenosine A1 receptors. This study supports the use of high-intensity exercise as an adjunct therapy for CRPS-I treatment.