Delta opioid receptors on nociceptive sensory neurons mediate peripheral endogenous analgesia in colitis

Background Inflammatory visceral pain is endogenously controlled by enkephalins locally released by mucosal CD4+ T lymphocytes in mice. The present study aimed at identifying opioid receptor(s) expressed on nociceptive sensory nerves involved in this peripheral opioid-mediated analgesia. Methods The peripheral analgesia associated with the accumulation of CD4+ T lymphocytes within the inflamed colonic mucosa was assessed in conditional knockout mice specifically deleted for either of the two opioid receptors for enkephalins (i.e., µ (MOR) and δ (DOR) receptors) in Nav1.8-expressing sensory neurons in the dextran sulfate sodium (DSS)-induced colitis model. Results Endogenous analgesia is lost in conditional knockout mice for DOR, but not MOR at the later phase of the DSS-induced colitis. The absence of either of the opioid receptors on sensory nerves had no impact on both the colitis severity and the rate of T lymphocytes infiltrating the inflamed colonic mucosa. Conclusion The key role of DOR on primary afferents in relieving intestinal inflammatory pain opens new therapeutic opportunities for peripherally restricted DOR analgesics to avoid most of the side effects associated with MOR-targeting drugs used in intestinal disorders.

Relationship between Oxytocin and Osteoarthritis: Hope or Despair?

Oxytocin (OT) is involved in breastfeeding and childbirth and appears to play a role in regulating the bone matrix. OT is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and is released in response to numerous stimuli. It also appears to be produced by osteoblasts in the bone marrow, acting as a paracrine–autocrine regulator of bone formation. Osteoarthritis (OA) is a disease of the whole joint. Different tissues involved in OA express OT receptors (OTRs), such as chondrocytes and osteoblasts. This hormone, which levels are reduced in patients with OA, appears to have a stimulatory effect on chondrogenesis. OT involvement in bone biology could occur at both the osteoblast and chondrocyte levels. The relationships between metabolic syndrome, body weight, and OA are well documented, and the possible effects of OT on different parameters of metabolic syndrome, such as diabetes and body weight, are important. In addition, the effects of OT on adipokines and inflammation are also discussed, especially since recent data have shown that low-grade inflammation is also associated with OA. Furthermore, OT also appears to mediate endogenous analgesia in animal and human studies. These observations provide support for the possible interest of OT in OA and its potential therapeutic treatment.

Natural Products with Analgesic Effect from Herbs and Nutraceuticals Used in Traditional Chinese Medicines

Introduction: Pain is one of the most common clinical symptoms . This review aims to describe research on herbs and their active ingredients in treating pain and provide a valuable reference for the development and utilization of analgesic traditional Chinese medicine (TCM). Materials and Methods: The literature search was performed from 1995 to October 2016, covering the relevant studies that concern the treatment of pain with TCM. Active ingredients extracted from TCM with analgesic activity are summarized and classified into six categories, including polysaccharides, saponins, alkaloids, flavonoids, terpenoids, and other constituents. Results: There are two pathways constituting the analgesic mechanisms of TCM: through the central nervous system and the peripheral nervous system. The former pathway includes increasing the content of endogenous analgesic substances like opiate peptide, cutting down the second messenger of neurotransmitter like nitric oxide (NO), reducing the content of prostaglandin E2 (PGE2) in brain tissues, blocking the central calcium channel, reducing excitatory amino acids in brain tissues, inhibiting their receptors and raising the content of the central 5-hydroxytryptamine (5-HT). The latter one usually involves the decrease in the secretion of peripheral algogenic substances, the induction of pain-sensitive substances, the accumulation of a local algogenic substance, the increase in the release of peripheral endogenous analgesia materials and the regulation of c-Fos gene (immediate early gene).