4.4 Article

The central effects of buspirone on abdominal pain in rats

Journal

NEUROGASTROENTEROLOGY AND MOTILITY
Volume 30, Issue 11, Pages -

Publisher

WILEY
DOI: 10.1111/nmo.13431

Keywords

abdominal pain; buspirone; irritable bowel syndrome; neurons; ventrolateral medulla

Funding

  1. Program of Fundamental Scientific Research of State Academies for 2013-2020 [GP-14, 64]
  2. Russian Foundation for Basic Research (RFBR) [11-04-00746]

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Background Buspirone, a partial agonist of the 5-HT1a receptor (5-HT1aR), 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-HT(1a)Rs, specifically located within the ventrolateral medulla (VLM). The most animal studies of the 5-HT1aR involvement in pain control have been carried out with somatic behavioral tests. The 5-HT1aR contribution in visceral pain transmission within the VLM is unclear. The objective of our study was to evaluate the 5-HT1aR contribution in abdominal pain transmission within the VLM. MethodsResultsUsing 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-HT1aR blockade by antagonist, WAY 100,635. The CRD induced a significant increase in VLM neuron activity up to 201.518.0% 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. ConclusionBuspirone 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-HT(1a)Rs in mediating pain control networks.

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