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Updated: Jul 13, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Analgesia induced by morphine microinjected into the nucleus raphe magnus: effects on tonic pain
Christian Dualé1, Fernando Sierralta, Radhouane Dallel
1INSERM, E216, Clermont-Ferrand, F-63000, France. cduale@chu-clermontferrand.fr
Abstract:
One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p <0.0001 compared to control), analgesia on the response to formalin was also observed for both early (p = 0.007) and late responses (p = 0.02). However, the response to formalin was not completely blunted. These results suggest that the Nucleus Raphe Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.
Insights
Morphine in the Nucleus Raphe Magnus provides analgesia for both transient and tonic pain in rats. However, its effect on tonic pain is not complete, suggesting other sites of action for morphine-induced analgesia.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- The Nucleus Raphe Magnus is a potential site for morphine's analgesic effects, demonstrated in transient pain models.
- Investigating morphine's action in the Nucleus Raphe Magnus is crucial for understanding pain management.
Purpose of the Study:
- To determine if morphine administered to the Nucleus Raphe Magnus exhibits analgesic properties in a tonic pain model.
- To compare the analgesic efficacy of morphine in the Nucleus Raphe Magnus for both phasic and tonic pain stimuli.
Main Methods:
- Microinjection of morphine (5 microg) or saline into the Nucleus Raphe Magnus of rats.
- Assessment of analgesic effects using tail-flick test (phasic pain) and formalin injection in the orofacial region (tonic pain).
Main Results:
- Morphine in the Nucleus Raphe Magnus significantly reduced the tail-flick response, indicating strong analgesia in phasic pain.
- Analgesia was observed for both early and late phases of the formalin test (tonic pain), though not completely abolishing the response.
- Statistical significance was noted for tail-flick (p <0.0001), early formalin (p = 0.007), and late formalin responses (p = 0.02).
Conclusions:
- The Nucleus Raphe Magnus plays a role in morphine-induced analgesia for both transient and tonic pain.
- The incomplete blunting of the tonic pain response suggests that the Nucleus Raphe Magnus is not the sole site of action for morphine's clinical analgesic effects.
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