The central effects of buspirone on abdominal pain in rats

Abstract

Buspirone, a partial agonist of the 5-HT1a receptor (5-HT1a R), owing to potential antinociceptive properties may be useful in treatment of abdominal pain in IBS patients. The pain-related effects of buspirone are mediated via the 5-HT1a Rs, specifically located within the ventrolateral medulla (VLM). The most animal studies of the 5-HT1a R involvement in pain control have been carried out with somatic behavioral tests. The 5-HT1a R contribution in visceral pain transmission within the VLM is unclear. The objective of our study was to evaluate the 5-HT1a R contribution in abdominal pain transmission within the VLM. Using animal model of abdominal pain (urethane-anaesthetized rats), based on the noxious colorectal distension (CRD) as pain stimulus we studied effects of buspirone (1.0-4.0mgkg-1 , iv) on the CRD-induced VLM neuron and blood pressure responses as markers of abdominal pain before and after the 5-HT1a R blockade by antagonist, WAY 100,635. The CRD induced a significant increase in VLM neuron activity up to 201.5±18.0% and depressor reactions up to 68±1.8% of baseline. Buspirone (1.0-4.0mgkg-1 , iv) resulted in an inhibition of the CRD-induced neuron responses which were changed inversely with dose increase and decreased depressor reactions directly with dose increase. These effects were antagonized by intracerebroventricular WAY 100,635. Buspirone exerts complex biphasic action on the pain-related VLM neuron activity inversely depending on dose. The final effect of buspirone depends on the functional balance between of activation the pre- and postsynaptic 5-HT1a Rs in mediating pain control networks.