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Effects of neuropeptide FF analogs on morphine analgesia in the nucleus raphe dorsalis
1Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, Toulouse, France.
Abstract:
The effect of microinfusion into the nucleus raphe dorsalis (DR) of neuropeptide FF (NPFF) analogs on the antinociceptive effects of morphine was evaluated in rats, using the tail-immersion test. infusion of morphine into the DR induced a dose-dependent analgesia significantly reversed by co-infusion of 2.5 nmol opioid antagonist, naloxone. Similarly, 2.5 nmol NPFF and (1DMe)Y8Fa(D-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2) or (3D)Y8Fa(D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2), two neuropeptide FF analogs, inhibited morphine analgesia, although these peptides had no effect on nociceptive thresholds. This anti-opioid effect is indirect since NPFF analogs displayed no significant affinity towards mu and delta opioid binding sites in the DR. After intracerebroventricular infusion, morphine produced the same degree of analgesia as that measured after infusion into the nucleus raphe dorsalis and both NPFF analogs reversed morphine antinociception. This result is the first direct evidence that neuropeptide FF may act on opioid system at the DR and that several nuclei are involved in the suppression of morphine-induced antinociception.
Insights
Neuropeptide FF (NPFF) analogs were found to inhibit morphine
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid analgesics like morphine are crucial for pain management.
- The nucleus raphe dorsalis (DR) is implicated in opioid-mediated pain relief.
- Neuropeptide FF (NPFF) systems are known to modulate pain perception.
Purpose of the Study:
- To investigate the effect of NPFF analogs on morphine-induced analgesia in rats.
- To determine if NPFF analogs interact with opioid receptors in the DR.
- To explore the role of NPFF in the central nervous system's control of pain.
Main Methods:
- Microinfusion of morphine and NPFF analogs into the rat nucleus raphe dorsalis (DR).
- Evaluation of antinociception using the tail-immersion test.
- Assessment of NPFF analog affinity for mu and delta opioid binding sites.
- Intracerebroventricular (ICV) infusion of morphine and NPFF analogs.
Main Results:
- Morphine infusion into the DR produced dose-dependent analgesia, blocked by naloxone.
- NPFF analogs inhibited morphine analgesia in the DR without affecting nociceptive thresholds.
- NPFF analogs did not bind to mu or delta opioid receptors in the DR.
- Both NPFF analogs reversed morphine antinociception after ICV infusion.
Conclusions:
- Neuropeptide FF (NPFF) analogs can suppress morphine-induced analgesia.
- NPFF may act indirectly on the opioid system within the nucleus raphe dorsalis (DR).
- Multiple brain nuclei are involved in modulating morphine's pain-relieving effects.