Abstract |
We here studied the involvement of spinally located 5-HT(1A) and opioid receptors, in the paradoxical effects that their activation can produce on nociception. Intrathecal (i.t.) injection of the 5-HT(1A) receptor agonist 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT) (1-10 microg) induced analgesic effects in the formalin model of tonic pain whereas in the paw pressure test, it decreased the vocalization threshold. In this latter test, i.t. 8-OH-DPAT also markedly reduced the analgesic effect of systemic morphine (5-10 mg/kg, s.c.). At 10 microg, 8-OH-DPAT totally abolished the effect of 5 mg/kg of morphine; this inhibitory effect was antagonized by pre-treatment with 0.63 mg/kg of the 5-HT(1A) antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide-trihydrochloride). In contrast, the i.t. injection of WAY-100635 (1-10 microg) dose-dependently potentiated the antinociceptive activity of a dose of morphine (2.5 mg/kg, s.c.). Furthermore, WAY-100635 (10 microg, i.t.) potentiated morphine analgesia in morphine-tolerant rats. These findings demonstrate that 5-HT(1A) receptor agonists can act in the spinal cord to produce both hyper- and hypo-algesic effects and play a major role in the opioid analgesia and tolerance.
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Authors | Laurent Bardin, Francis C Colpaert |
Journal | European journal of pain (London, England)
(Eur J Pain)
Vol. 8
Issue 3
Pg. 253-61
(Jun 2004)
ISSN: 1090-3801 [Print] England |
PMID | 15109976
(Publication Type: Journal Article)
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Chemical References |
- Analgesics, Opioid
- Piperazines
- Pyridines
- Receptors, Opioid
- Serotonin Antagonists
- Receptor, Serotonin, 5-HT1A
- N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
- Morphine
- 8-Hydroxy-2-(di-n-propylamino)tetralin
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Topics |
- 8-Hydroxy-2-(di-n-propylamino)tetralin
(pharmacology)
- Afferent Pathways
(cytology, drug effects, metabolism)
- Analgesics, Opioid
(pharmacology)
- Animals
- Dose-Response Relationship, Drug
- Drug Interactions
(physiology)
- Drug Tolerance
(physiology)
- Injections, Spinal
- Male
- Morphine
(pharmacology)
- Pain
(drug therapy, metabolism, physiopathology)
- Pain Measurement
(drug effects)
- Pain Threshold
(drug effects, physiology)
- Piperazines
(pharmacology)
- Pyridines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT1A
(drug effects, metabolism)
- Receptors, Opioid
(drug effects, metabolism)
- Serotonin Antagonists
(pharmacology)
- Spinal Cord
(drug effects, physiopathology)
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