Abstract | BACKGROUND: METHODS: After L5 spinal nerve ligation injury, male Sprague-Dawley rats were subjected to behavioral testing, in vivo microdialysis of the spinal dorsal horn to determine serotonin ( 5-hydroxytryptamine [5-HT]) and noradrenaline release, and immunohistochemistry (n = 6 in each group). RESULTS: Intraperitoneal administration of morphine (1, 3, or 10 mg/kg) produced analgesic effects in normal and spinal nerve ligation rats, but the effects were greater in normal rats (P < 0.001). Morphine increased 5-HT release (450 to 500% of the baseline), but not noradrenaline release, in the spinal dorsal horn via activation of serotonergic neurons in the rostral ventromedial medulla. Intrathecal pretreatment with ondansetron (3 μg), a 5-HT3 receptor antagonist, or 5,7-dihydroxytryptamine creatinine sulfate (100 μg), a selective neurotoxin for serotonergic terminals, attenuated the analgesic effect of morphine (10 mg/kg) in normal rats but increased the analgesic effect of morphine in spinal nerve ligation rats (both P < 0.05). CONCLUSIONS: Systemic administration of morphine increases 5-HT levels in the spinal cord, and the increase in 5-HT contributes to morphine-induced analgesia in the normal state but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The plasticity of the descending serotonergic system may contribute to the reduced efficacy of systemic morphine in neuropathic pain.
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Authors | Masafumi Kimura, Hideaki Obata, Shigeru Saito |
Journal | Anesthesiology
(Anesthesiology)
Vol. 121
Issue 2
Pg. 362-71
(Aug 2014)
ISSN: 1528-1175 [Electronic] United States |
PMID | 24887968
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Opioid
- Receptors, Serotonin, 5-HT3
- Serotonin Antagonists
- Serotonin
- Ondansetron
- Morphine
- Norepinephrine
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Topics |
- Analgesics, Opioid
(pharmacology)
- Animals
- Behavior, Animal
(drug effects)
- Immunohistochemistry
- Injections, Intraperitoneal
- Injections, Spinal
- Male
- Microdialysis
- Morphine
(pharmacology)
- Norepinephrine
(metabolism)
- Ondansetron
(administration & dosage, pharmacology)
- Pain Measurement
(drug effects)
- Pain Threshold
(drug effects)
- Peripheral Nerve Injuries
(physiopathology)
- Posterior Horn Cells
(drug effects, metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Serotonin, 5-HT3
(drug effects)
- Serotonin
(metabolism)
- Serotonin Antagonists
(administration & dosage, pharmacology)
- Spinal Cord
(drug effects, metabolism, physiopathology)
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