Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation.

TLDR

Localized antinociception in inflamed tissue can be mediated by both exogenous and endogenous opioids, with cold‑water swim‑induced effects arising from non‑pituitary sources. The study aims to demonstrate that immune cells infiltrating inflamed tissue contain elevated opioid peptides. The authors quantified opioid peptide levels in infiltrating immune cells within inflamed tissue. They found that immune‑cell–derived opioid peptides act on opioid receptors on peripheral sensory nerve terminals to mediate cold‑water swim‑induced antinociception, as blockade with antibodies or cyclosporine abolished the effect.

Abstract

Exogenous opioids can produce localized opioid receptor-mediated antinociception in peripheral inflamed tissue. Previous studies show that activation of endogenous opioids by a cold water swim in rats with hind paw inflammation results in a similar local antinociceptive effect but suggest that pituitary-adrenal opioid pools are not directly involved in producing this effect. Here we show increased amounts of opioid peptides in immune cells infiltrating the inflamed tissue. Furthermore, we demonstrate immunoreactive opioid receptors on peripheral terminals of sensory neurons. The local administration of antibodies against opioid peptides or receptors or systemic pretreatment with the immunosuppressant cyclosporine blocks cold water swim-induced antinociception. These findings suggest that antinociception in inflammation can be brought about by endogenous opioids from immune cells interacting with opioid receptors on peripheral sensory nerves.