Electroacupuncture inhibits visceral pain via adenosine receptors in mice with inflammatory bowel disease

Abstract

To investigate the involvement of peripheral adenosine receptors in the effect of electroacupuncture (EA) on visceral pain in mice with inflammatory bowel disease (IBD). 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was used to induce the visceral pain model. EA (1 mA, 2 Hz, 30 min) treatment was applied to bilateral acupoints BDachangshu^(BL25) 1 day after TNBS injection once daily for 7 consecutive days. Von Frey filaments were used to measure the mechanical pain threshold. Western blot was used to detect the protein expression levels of adenosine 1 receptor (A1R), adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), adenosine 3 receptor (A3R), substance P (SP), and interleukin 1 beta (IL-1β) in colon tissue. EA significantly ameliorated the disease-related indices and reduced the expression of SP and IL-1β in the colon tissues of mice with IBD. EA increased the expression of A1R, A2aR, and A3R and decreased the expression of A2bR in the colon tissue. Furthermore, the administration of adenosine receptor antagonists influenced the effect of EA. EA can inhibit the expression of the inflammatory factors SP and IL-1β by regulating peripheral A1, A2a, A2b, and A3 receptors, thus inhibiting visceral pain in IBD mice.

Inflammatory Bowel Diseases: It's Time for the Adenosine System

“…In particular, the engagement of A 2A or A 3 receptors by selective agonists appear to be an interesting method of management for IBD patients displaying an increased gut motility and diarrhea (77,79). A number of encouraging data are emerging about the modulatory role of adenosine receptors on visceral sensitivity (71,72). The A 3 receptor agonists highlighted a pain-relieving mediated through N-type Ca 2+ channel block and action potential inhibition, suggesting the A 3 receptor agonists as an innovative approach to manage the visceral pain (59).…”

“…Sohn et al reported that the intrathecal administration of the A 1 receptor agonist R-PIA, but not the A 2A receptor agonist CGS-21680 hydrochloride, decreased the visceromotor responses (70). Currently, some authors paid greater attention to the potential anti-nociceptive effects of A 3 agonists (71,72). For instance, Hou et al demonstrated the analgesic effects of A 3 receptor agonists in a mouse model of visceral pain following experimental colitis (71).…”

“…Currently, some authors paid greater attention to the potential anti-nociceptive effects of A 3 agonists (71,72). For instance, Hou et al demonstrated the analgesic effects of A 3 receptor agonists in a mouse model of visceral pain following experimental colitis (71). At present, no data are available about the putative analgesic effect of A 2A ligands on abdominal pain associated with experimental colitis.…”

Control of Gut Inflammation by Modulation of Purinergic Signaling

“…The antalgic effect was mediated by inhibition of release of the pro-inflammatory factors substance P (SP) and IL-1β. This salutary effect was partially abrogated in the presence of adenosine receptors antagonists (47).…”

The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A3 Receptor Agonist, in a Rat Model of Colitis

“…Several authors have highlighted the potential anti-nociceptive effects of A 3 AR activation [ 13 , 14 ]. For instance, Hou et al [ 13 ] described the involvement of A 3 ARs in the beneficial effects exerted by electroacupuncture on the hypersensitivity induced by colitis in mice [ 13 ].…”