A dual effect of 5-HT1B receptor stimulation on nociceptive dorsal horn neurones in rats.
In this study the modulatory effects of 5-HT1B receptor activation on wide dynamic range neurones in the spinal cord were studied. Extracellular single unit recordings of dorsal horn neurones were performed in intact urethane-anaesthetized female Sprague-Dawley rats, and the receptive field distally on one hind paw was electrically stimulated with needle electrodes applied to the skin. The 5-HT1B receptor agonist, CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one), the 5-HT1A/B receptor antagonist cyanopindolol, and the 5-HT1A receptor antagonist WAY100635 (N-[2-[4-(2-methoxypheny])-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), were applied directly onto the spinal cord, and single unit responses were counted separately for A beta-, A delta-, C-fibre responses and post-discharge according to the latencies. A dual effect of CP-93,129 was observed: 50 nmol CP-93,129 caused a clear inhibition of the A delta-fibre responses, whereas 50 and 150 nmol CP-93,129 produced a dose-dependent increase in post-discharge without affecting A beta- and C-fibre responses. Application of 50 nmol cyanopindolol or 50 nmol WAY 100635 alone did not affect neither the neuronal A-fibre nor the C-fibre responses, but when 50 nmol cyanopindolol was coadministered with 50 nmol CP-93,129 the effect of CP-93,129 alone was blocked: the A delta-fibre response was not inhibited and the post-discharge was not increased. In contrast, 50 nmol WAY100635 did not block the effect of 50 nmol CP-93,129 when the two drugs were coadministered. These results suggest that stimulation of the 5-HT1B receptors may have both pro- and antinociceptive effects on wide dynamic range neurones in the dorsal horn after repeated electrical stimulation.
Gjerstad
J
J
Department of Physiology, University of Bergen, Norway. johannes.gjerstad@pki.uib.no
Tjølsen
A
A
Hole
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C047975:cyanopindolol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D010869:Pindolol