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Inflammation without pain: Immune-derived opioids hold the key
Simona E Carbone1,2, Daniel P Poole1,2
1Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic, Australia.
Neurogastroenterology and Motility
|January 31, 2020
Summary
Chronic inflammatory bowel disease (IBD) may be painless due to an endogenous analgesic system. Immune cells produce opioids that suppress visceral hypersensitivity, offering potential new pain relief strategies.
Area of Science:
- Immunology
- Neurogastroenterology
- Pain Research
Background:
- Visceral pain is common in acute inflammatory bowel disease (IBD), but chronic IBD is often painless despite active inflammation.
- This suggests an endogenous analgesic system may be active in chronic IBD, counteracting altered nociceptive signaling.
Purpose of the Study:
- To investigate the immune-mediated mechanisms underlying visceral pain suppression in chronic IBD.
- To explore the role of endogenous opioids produced by immune cells in managing visceral hypersensitivity.
Main Methods:
- Utilized the IL-10-piroxicam model of chronic colitis, characterized by immune suppression.
- Administered a peripherally restricted opioid receptor antagonist to assess its effect on visceral pain responses during active inflammation.
- Analyzed immune cell populations, specifically colitogenic CD4+ T cells, in the colonic mucosa.
Main Results:
- Mice with active chronic colitis exhibited normal visceral pain responses, similar to healthy controls.
- Treatment with an opioid receptor antagonist induced significant visceral hypersensitivity, indicating opioid-mediated analgesia.
- Endogenous opioids produced by mucosal CD4+ T cells were identified as the source of this analgesic effect.
Conclusions:
- Immune cells, particularly CD4+ T cells, play a crucial role in suppressing visceral hypersensitivity in chronic IBD through opioid production.
- This immune-mediated analgesic system offers potential therapeutic targets for managing chronic IBD pain.
- Pharmacological strategies mimicking this endogenous system could provide sustained relief for IBD-associated pain.
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