The role of spinal inhibitory neuroreceptors in the antihyperalgesic effect of warm water immersion therapy

Abstract Objective Warm water immersion therapy (WWIT) has been widely used in the treatment of various clinical conditions, with analgesic and anti-inflammatory effects. However, its mechanism of action has not been fully investigated. The present study analyzed the role of spinal inhibitory neuroreceptors in the antihyperalgesic effect of WWIT in an experimental model of inflammatory pain. Methods Mice were injected with complete Freund’s adjuvant (CFA; intraplantar [i.pl.]). Paw withdrawal frequency to mechanical stimuli (von Frey test) was used to determine: (1) the effect of intrathecal (i.t.) preadministration of naloxone (a non-selective opioid receptor antagonist; 5 µg/5 µl), (2); AM281 (a selective cannabinoid receptor type 1 [CB1] antagonist; 2 µg/5 µl), (3); and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/5 µl), on the antihyperalgesic (pain-relieving) effect of WWIT against CFA-induced hyperalgesia. Results Intrathecal naloxone, AM281, and DPCPX significantly prevented the antihyperalgesic effect of WWIT. This study suggests the involvement of spinal (central) receptors in the antihyperalgesic effect of WWIT in a model of inflammatory pain. Conclusions Taken together, these results suggest that opioid, CB1, and A1 spinal receptors might contribute to the pain-relieving effect of WWIT.