Effects of spinally administered P2X receptor agonists and antagonists on the responses of dorsal horn neurones recorded in normal, carrageenan-inflamed and neuropathic rats.
1. The function and role of P2X receptors in the spinal transmission of nociception was investigated using the selective P2X receptor agonists, alpha,beta-methylene ATP (alpha,beta-me ATP) and beta, gamma-methylene-L-ATP (beta,gamma-me-L-ATP) and the P2X receptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and suramin. 2. Intrathecal administration of 5 and 50 microg of beta,gamma-me-L-ATP produced a significant facilitation of the C-fibre evoked response and a tendency towards increased excitability of the post-discharge, but not Abeta-fibre evoked response of dorsal horn neurones recorded in normal animals. Administration of similar doses of alpha,beta-me ATP did not produce an overall change in the response of the neuronal population. 3. Peripheral administration of 20 microg of these agonists into the paw of the rat evoked firing in the dorsal horn neurones. 4. Intrathecal administration of the antagonists, suramin (50 and 500 microg) and PPADS (5, 50 and 500 microg), to normal animals and to animals with a model of neuropathy induced by spinal nerve ligation did not alter the evoked neuronal responses. In contrast, intrathecal administration of 500 microg of suramin to animals 3 h after the induction of carrageenan inflammation produced a significant inhibition of the C-fibre evoked response of the neurones. Similar inhibitions were also seen following high doses of intrathecal PPADS, although this did not reach significance. 5. These results suggest that spinal P2X receptors may play a role in the modulation of spinal nociceptive transmission following the development of inflammation, but that these receptors play at most a minor role in spinal nociceptive processing in normal and neuropathic animals.
Stanfa
L C
LC
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT. l.stanfa@ucl.ac.uk
Kontinen
V K
VK
Dickenson
A H
AH
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D002351:Carrageenan; D004594:Electrophysiology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000473:pathology; D013498:Suramin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D002351:Carrageenan; C002630:alpha,beta-methyleneadenosine 5'-triphosphate