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Biphasic effects of intracerebroventricular interleukin-1 beta on mechanical nociception in the rat
K Yabuuchi1, A Nishiyori, M Minami
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Insights
Interleukin-1 beta exhibits dose-dependent effects on pain sensitivity in rats, causing hyperalgesia at low doses and analgesia at high doses. These effects are mediated by brain receptors and involve specific signaling pathways.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine implicated in pain modulation.
- The central nervous system's role in mediating cytokine effects on pain is not fully understood.
Purpose of the Study:
- To investigate the dose-dependent effects of central interleukin-1 beta administration on mechanical nociception in rats.
- To elucidate the receptor-mediated pathways involved in IL-1β's actions on pain.
Main Methods:
- Intracerebroventricular (i.c.v.) injections of varying doses of IL-1β in rats.
- Assessment of mechanical nociceptive threshold using the paw-pressure test.
- Administration of IL-1 receptor antagonist, alpha-helical-corticotropin-releasing factor [9-41], and sodium salicylate to investigate mechanisms.
Main Results:
- Low doses (10-100 pg/rat) of i.c.v. IL-1β induced hyperalgesia (increased pain sensitivity).
- High doses (1-10 ng/rat) of i.c.v. IL-1β produced an analgesic effect (pain reduction).
- Both hyperalgesic and analgesic effects were blocked by IL-1 receptor antagonist and alpha-helical-CRF [9-41], suggesting central mediation.
- Sodium salicylate inhibited hyperalgesia but not analgesia, implicating prostaglandins in the hyperalgesic effect.
Conclusions:
- Interleukin-1 beta exerts biphasic effects on mechanical pain thresholds via central IL-1 receptors.
- A corticotropin-releasing factor-mediated pathway is involved in IL-1β's modulation of pain.
- Prostaglandins may mediate the hyperalgesic actions of IL-1 beta.
Abstract:
The effects of interleukin-1 beta on the mechanical nociceptive threshold in rat were examined using the paw-pressure test. An intracerebroventricular (i.c.v.) injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia to mechanical stimuli. Higher doses of interleukin-1 beta (1 and 10 ng/rat) induced an analgesic effect. The coadministration of the interleukin-1 receptor antagonist completely antagonized the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing factor [9-41] 15 min prior to interleukin-1 beta administration completely blocked the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of sodium salicylate 15 min prior to interleukin-1 beta administration inhibited the hyperalgesic effect of interleukin-1 beta, but not the analgesic effect. These results suggest that interleukin-1 beta produces biphasic effects on the mechanical nociceptive threshold through the interleukin-1 receptor in the brain and that a corticotropin-releasing factor-mediated pathway is involved. Furthermore, the hyperalgesic effect of interleukin-1 beta may be mediated by prostaglandins.
