Peripheral neurobiologic mechanisms of antiallodynic effect of warm water immersion therapy on persistent inflammatory pain

Abstract

Water immersion is widely used in physiotherapy and might relieve pain, probably by activating several distinct somatosensory modalities, including tactile, pressure, and thermal sensations. However, the endogenous mechanisms behind this effect remain poorly understood. This study examined whether warm water immersion therapy (WWIT) produces an antiallodynic effect in a model of localized inflammation and whether peripheral opioid, cannabinoid, and adenosine receptors are involved in this effect. Mice were injected with complete Freund's adjuvant (CFA; intraplantar; i.pl.). The withdrawal frequency to mechanical stimuli (von Frey test) was used to determine 1) the effect of WWIT against CFA-induced allodynia and 2) the effect of i.pl. preadministration of naloxone (a nonselective opioid receptor antagonist; 5 µg/paw), caffeine (a nonselective adenosine receptor antagonist; 150 nmol/paw), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/paw), and AM630 (a selective cannabinoid receptor type 2 antagonist; 4 µg/paw) on the antiallodynic effect of WWIT against CFA-induced allodynia. Moreover, the influence of WWIT on paw inflammatory edema was measured with a digital micrometer. WWIT produced a significant time-dependent reduction of paw inflammatory allodynia but did not influence paw edema induced by CFA. Naloxone, caffeine, DPCPX, and AM630 injected in the right, but not in the left, hind paw significantly reversed the antiallodynic effect of WWIT. This is the first study to demonstrate the involvement of peripheral receptors in the antiallodynic effect of WWIT in a murine model of persistent inflammatory pain.

Adenosine for postoperative analgesia: A systematic review and meta-analysis

“…The present meta-analysis also showed that exogenous ADO relieved postoperative pain by 24h, thereby reducing opioid requirements. These results were in accordance with the studies by Katz et al and Martins et al [26, 27] in that endogenous ADO production was found to improve mechanical hyperalgesia. The first postoperative analgesic requirement was about 25 times longer than in the remifentanil subgroup.…”

High‐intensity swimming exercise reduces inflammatory pain in mice by activation of the endocannabinoid system

“…Mice were injected (intraplantar [i.pl.]) with 20 µL 80% CFA ( Mycobacterium tuberculosis ) as described by Meotti et al 21 and Martins et al 22 CFA produced significant hindpaw swelling and hyperalgesia. To evaluate mechanical hyperalgesia, the animals were tested for response frequency to mechanical stimuli with calibrated von Frey filaments [VFFs] applied to the plantar aspect of the right hindpaw.…”

“…The right hindpaw was stimulated with a constant pressure of 0.4 g with the VFF (Stoelting). The response frequency to 10 applications was used as an indicator of nociceptive behavior, and the results are expressed as the percentage of withdrawal frequency 22 . Mechanical hyperalgesia tests were performed before (baseline) and 24 hours after i.pl.…”

“…Paw edema was measured as the difference between paw thickness (in micrometers) compared to baseline, using a digital micrometer. The difference between the groups indicated the degree of inflammation 22,23 . Tests were performed before (baseline) and 24 hours after i.pl.…”

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

“…Gabapentin is also used to treat restless leg syndrome, which was recently reported to have a MoA involving the A 1 AR [85]. One of the more unusual proposals is a peripheral adenosinergic MoA of warm-water-immersion therapy for treating persistent inflammatory pain, based on the antagonism by locally administered DPCPX (10 nmol/paw) [86].…”