Accepted

Irritable bowel syndrome (IBS) can be caused by abnormal bowel movements, altered brain-gut axis, gut microbiota change, and low levels of inflammation or immune activation. The intake of food containing much fiber and lactic acid bacteria (LABs) can alleviate IBS.

The addition of morphine to neuraxial anaesthesia leads to improved postoperative analgesia and lower opioid consumption, but is often accompanied by pruritus. Studies on preventing or treating pruritus show contradictory results. Our objective was to identify effective drugs for the prevention or treatment of pruritus by a scoping review of clinical trials. A systematic literature search was conducted in PubMed, Embase and Web of Science. We identified clinical trials investigating the prevention or treatment of neuraxial morphine-induced pruritus in adults. Systematic reviews and meta-analyses were screened for eligible studies. One-hundred-and-four articles were included covering 13 pharmacological groups. We conclude that dopamine antagonists, µ-opioid agonist/antagonists and neuraxial or orally administered µ-opioid antagonists prevent pruritus caused by neuraxial morphine regardless of the timing of administration. In the reviewed literature, 5HT3-antagonists prevent neuraxial morphine-induced pruritus when administered before morphine administration. For the treatment of neuraxial morphine-induced pruritus, only nalbuphine appears to be consistently effective. More research is needed to find the most effective doses and the optimal timing of the effective medication.

In view of concerns about the harmful effects of long-term use and patient misuse of opioids in chronic non-malignant pain, this study provides insight into patients' perspectives on their experience of living with chronic non-malignant pain (CNMP), prescribed opioid use, and optimisation.

Obesity is a significant health concern as a result of poor-quality diet, for example, high-fat diet (HFD). Although multiple biological and molecular changes have been identified to contribute to HFD-induced pain susceptibility, the mechanisms are not fully understood. Here, we show that mice under 8 weeks of HFD were sensitive to mechanical and thermal stimuli, which was coupled with an accumulation of branched-chain amino acids (BCAAs) in lumbar dorsal root ganglia (DRG) due to local BCAA catabolism deficiency. This HFD-induced hyperalgesic phenotype could be exacerbated by supply of excessive BCAAs or mitigated by promotion of BCAA catabolism BT2 treatment. In addition, our results suggested that HFD-related pain hypersensitivity was associated with a pro-inflammatory status in DRG, which could be regulated by BCAA abundance. Therefore, our study demonstrates that defective BCAA catabolism in DRG facilitates HFD-induced pain hypersensitivity by triggering inflammation. These findings not only reveal metabolic underpinnings for the pathogenesis of HFD-related hyperalgesia but also offer potential targets for developing diet-based therapy of chronic pain.

Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we and others have also demonstrated that non-selective CB agonists attenuate morphine antinociceptive tolerance. Activation of cannabinoid CB2 receptors reverses allodynia and hyperalgesia in models of chronic pain, and co-administration of morphine with CB2 receptor selective agonists has been shown to be synergistic. CB2 receptor activation has also been shown to reduce morphine-induced hyperalgesia in rodents, an effect attributed to CB2 receptor modulation of inflammation. In the present set of experiments, we tested both the acute and chronic interactions between morphine and the CB2 receptor selective agonist O-1966 treatments on antinociception and antinociceptive tolerance in C57Bl6 mice. Co-administration of morphine and O-1966 was tested under three dosing regimens: simultaneous administration, morphine pre-treated with O-1966, and O-1966 pre-treated with morphine. The effects of O-1966 on mu-opioid receptor binding were determined using [3H]DAMGO and [S]GTPγS binding assays, and these interactions were further examined by FRET analysis linked to flow cytometry. Results yielded surprising evidence of interactions between the CB2 receptor selective agonist O-1966 and morphine that were dependent upon the order of administration. When O-1966 was administered prior to or simultaneous with morphine, morphine antinociception was attenuated and antinociceptive tolerance was exacerbated. When O-1966 was administered following morphine, morphine antinociception was not affected and antinociceptive tolerance was attenuated. The [S]GTPγS results suggest that O-1966 interrupts functional activity of morphine at the mu-opioid receptor, leading to decreased potency of morphine to produce acute thermal antinociceptive effects and potentiation of morphine antinociceptive tolerance. However, O-1966 administered after morphine blocked morphine hyperalgesia and led to an attenuation of morphine tolerance, perhaps due to well-documented anti-inflammatory effects of CB2 receptor agonism.