Activation of μ opioid receptors modulates inflammation in acute experimental colitis

Abstract

Background-μ opioid receptors (μORs) are expressed by neurons and inflammatory cells and mediate immune response. We tested whether activation of peripheral μORs ameliorates the acute and delayed phase of colitis.

Anti-Inflammatory Properties of the Enaminone E121 in the Dextran Sulfate Sodium (DSS) Colitis Model

“…The colonic levels of various caspases were shown to be increased post colitis induction. For example, the levels of caspase-3 [81, 82, 86], -7 [81] and -12 [76], and the cleaved form of caspases-1 [87, 88], -12, and -7 [73] were increased in the colonic tissues in various animal models of colitis, which are also in agreement with our findings in regard to caspase-3 and -8 levels (Fig 5). …”

“…Using the TNBS model, mesalamine treatment reduced colitis severity in mice in part through reducing BCL-2 colonic expression levels [80], which is in agreement with our finding using the DSS model where E121 also reduced its expression in the colon homogenate (Fig 5). The colonic levels of BCL-XL was shown to be unchanged [81], reduced [76], or increased [82] in animal models of colitis. Furthermore, its expression was also increased in colon biopsies taken from IBD patients [83].…”

Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells

“…NF- κB, an important nuclear transcriptional factor, its signaling pathway has been involved in numerous physiological processes, including regulation of inflammation response and innate immunity, and therefore may be participation in IBD in multiple ways [36]. The increased expression of NF-κB in the acute phase of colitis had been proved and is consistent with its role in the onset of experimental colitis [37].…”

Analgesia and mouse strain influence neuromuscular plasticity in inflamed intestine

“…However, many analgesic compounds do exert anti‐inflammatory effects. For example, selective μ‐opioid receptor agonists significantly reduced inflammation in TNBS colitis and in CD4+ T cell‐induced colitis . Similarly, our results show that buprenorphine typically caused significant change vs untreated, inflamed mice in both strains, while tramadol did not have significant effects.…”

“…The mechanism underlying these outcomes remains unclear, due to the complexity of the pharmacology of buprenorphine, as a non‐selective, mixed partial agonist and antagonist to the opioid receptors . Indeed, as a partial agonist of the μ‐opioid receptor, buprenorphine might be expected to ameliorate colitis, since activation of this pathway was beneficial in several models of visceral disease including TNBS, DSS, and ischemia/reperfusion injury . Furthermore, TNBS‐colitis was significantly more lethal in μ‐opioid receptor knock‐out mice, although the histological and morphological inflammatory scores were similar to control mice that received TNBS .…”