Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain.

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.

• Authors: Tansy Donovan-Rodriguez, Catherine E Urch, Anthony H Dickenson
• Journal: Neuroscience letters (Neurosci Lett) Vol. 393 Issue 2-3 Pg. 237-42 (Jan 30 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16256273 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serotonin Antagonists
• Serotonin
• Ondansetron

Topics

• Animals
• Behavior, Animal
• Bone Diseases (physiopathology)
• Cell Line, Tumor
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Evoked Potentials (drug effects, physiology, radiation effects)
• Functional Laterality
• Male
• Motor Activity (physiology)
• Neoplasms (complications, etiology, physiopathology)
• Ondansetron (administration & dosage)
• Pain (etiology, physiopathology)
• Pain Measurement (methods)
• Physical Stimulation (methods)
• Posterior Horn Cells (drug effects, physiopathology, radiation effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (physiology)
• Rotarod Performance Test (methods)
• Serotonin (metabolism)
• Serotonin Antagonists (administration & dosage)
• Temperature
• Time Factors