1. Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain.
- Author
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Donovan-Rodriguez T, Urch CE, and Dickenson AH
- Subjects
- Animals, Behavior, Animal, Cell Line, Tumor, Dose-Response Relationship, Drug, Evoked Potentials drug effects, Evoked Potentials physiology, Evoked Potentials radiation effects, Functional Laterality, Male, Motor Activity physiology, Neoplasms complications, Neoplasms etiology, Ondansetron administration & dosage, Pain etiology, Pain Measurement methods, Physical Stimulation methods, Posterior Horn Cells drug effects, Posterior Horn Cells physiopathology, Posterior Horn Cells radiation effects, Rats, Rats, Sprague-Dawley, Reaction Time physiology, Rotarod Performance Test methods, Serotonin Antagonists administration & dosage, Temperature, Time Factors, Bone Diseases physiopathology, Disease Models, Animal, Neoplasms physiopathology, Pain physiopathology, Serotonin metabolism
- Abstract
Descending modulation of spinal processing plays an important role in chronic pain states. Monoamine pathways comprise a major component of descending controls from the brainstem to the spinal cord. Recent emphasis has been on facilitatory actions mediated by the 5-HT3 receptor. We investigated the effects of spinally administered ondansetron, a selective 5-HT3 receptor antagonist, on electrical- and natural-evoked dorsal horn (DH) neuronal responses in a rat model of cancer-induced bone pain (CIBP). Injection of MRMT-1 cells into the tibiae of Sprague-Dawley rats was used to model CIBP, whilst sham-operated rats were injected with the cell medium alone. Behavioural testing at regular intervals monitored the development of mechanical allodynia, cold allodynia, and ambulatory-evoked pain. In vivo electrophysiology experiments were carried out 15-17 days after surgery, when there were significant behavioural and neuronal alterations in the cancer animals. Spinally administered ondansetron (10, 50, and 100 microg) had no effect on electrical-evoked neuronal responses, but significantly reduced mechanical- and thermal-evoked responses in both the groups of animals. Furthermore, the effects of ondansetron were significantly greater in cancer animals compared to shams. These results therefore suggest a role for descending serotonergic facilitation in CIBP.
- Published
- 2006
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