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-HT 3 receptor. We investigated the effects of spinally administered ondansetron, a selective 5-HT 3 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 μg) 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.