Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain.
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.
Donovan-Rodriguez
Tansy
T
Department of Pharmacology, University College, London WC1E 6BT, UK. tdonovan@umh.es
Urch
Catherine E
CE
Dickenson
Anthony H
AH
D000818:Animals; D001522:Behavior, Animal; D001847:Bone Diseases / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007839:Functional Laterality; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009369:Neoplasms / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D017294:Ondansetron / Q000008:administration & dosage; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D013696:Temperature; D013997:Time Factors
D012702:Serotonin Antagonists; D012701:Serotonin; D017294:Ondansetron