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

Xavier Mas-Orea1, Lilian Basso1,2, Catherine Blanpied1

  • 1Digestive Health Research Institute (IRSD), Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan BP 3028, 31024, Toulouse Cedex 3, France.

Journal of Neuroinflammation
|January 7, 2022
PubMed
Abstract

Insights

Delta opioid receptors (DOR) on sensory nerves are crucial for controlling inflammatory visceral pain in mice. Targeting DOR offers a promising therapeutic strategy for intestinal pain with fewer side effects.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Inflammatory visceral pain is modulated by enkephalins released from mucosal CD4+ T lymphocytes in mice.
  • The study investigates the specific opioid receptors involved in peripheral opioid-mediated analgesia.

Purpose of the Study:

  • To identify the opioid receptor(s) on nociceptive sensory nerves mediating peripheral analgesia.
  • To elucidate the role of mu (MOR) and delta (DOR) opioid receptors in T cell-mediated pain relief.

Main Methods:

  • Utilized conditional knockout mice lacking DOR or MOR in Na_v1.8-expressing sensory neurons.
  • Assessed peripheral analgesia in the dextran sulfate sodium (DSS)-induced colitis model.
  • Evaluated colitis severity and T lymphocyte infiltration rates.

Main Results:

  • Conditional knockout of DOR, but not MOR, abolished endogenous analgesia in later stages of DSS colitis.
  • Absence of DOR or MOR on sensory nerves did not affect colitis severity or T cell infiltration.
  • Peripheral analgesia relies on DOR expressed on sensory nerves.

Conclusions:

  • Delta opioid receptors (DOR) on primary afferent nerves play a key role in resolving intestinal inflammatory pain.
  • Peripherally restricted DOR agonists represent a potential therapeutic avenue for intestinal pain.
  • This approach may avoid side effects associated with centrally acting MOR agonists.
Keywords:
Intestinal inflammationNociceptorsOpioid receptorsOpioidsT lymphocytesVisceral pain

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