The involvement of metabotropic glutamate receptors and their intracellular signalling pathways in sustained nociceptive transmission in rat dorsal horn neurons.
The excitatory responses of individual dorsal horn neurons to cutaneous brush, repeated application of the C-fibre-selective chemical algogen, mustard oil, or to ionophoretic (1S,3R)-ACPD [a metabotropic glutamate receptor (mGluR) agonist] were monitored by extracellular recording. We have previously shown that the responses of dorsal horn neurons to mustard oil are inhibited by several selective antagonists of mGluRs. Effects of ionophoresis of the mGluR antagonists (R,S)-CHPG and L-AP3 and a range of selective inhibitors of intracellular signalling pathways were examined on evoked responses here. The results suggest that protein kinase C, phospholipase A2 and perhaps Ca2+/calmodulin kinase II play a role in mediating the sustained elevated activity of dorsal horn neurons that is incrementally elicited by repeated application of mustard oil, but probably make little contribution to sustained brush-evoked activity. Concurrence in the sensitivity of mustard oil- and (1S,3R)-ACPD-evoked activity to (R,S)-CHPG, L-AP3 and to inhibitors of intracellular signalling pathways, suggests that mGluRs are an important origin of these intracellular signals required for sustained nociception.
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
M R
MR
Young
S M
SM
Fleetwood-Walker
R
R
Mitchell
T
T
Dickinson
D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D009149:Mustard Plant; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010812:Physical Stimulation; D010936:Plant Extracts; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D010936:Plant Extracts; D010938:Plant Oils; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C027793:mustard oil