title: The coding of noxious mechanical and thermal stimuli of deep dorsal horn neurones is attenuated in NK1 knockout mice.
abstract: Previous behavioural evidence has shown that NK1 receptor gene knockout (NK1 -/-) mice display altered nociceptive responses following tissue or peripheral nerve injury. A single electrophysiological study reported an attenuation of wind-up and responses to mustard oil application. Although the behavioural results implicate SP and its receptor (NK1-R) in the transmission of noxious high intensity pain, little is known regarding the spinal neuronal substrates and the modalities involved. We have addressed this using in vivo electrophysiology and recordings of deep dorsal horn neurones in urethane-anaesthetised C57B6 x 129/sv mice to reveal a marked deficit in mechanical and thermal coding, selectively encompassing the suprathreshold range of noxious stimuli. The frequency-dependent increase in neuronal activity following repetitive C-fibre stimulation (wind-up) was also abolished in spinal neurones of NK1-R knockout mice. Quantification of the receptive field size of spinal neurones, mapped with low- and high-intensity mechanical punctate stimuli, revealed no differences between NK1 -/- and wildtype mice. We conclude that NK1-Rs are important in the high intensity noxious signalling of acute peripheral (mechanical/thermal) stimuli and this may result from the lack of wind-up and/or the disruption of spinal-bulbo-spinal loops.
authors: Department of Pharmacology, Medical Sciences Building, University College London, Gower Street, London WC1E 6BT, UK. ucklrsu@ucl.ac.uk
authors: Rie
authors: R
authors: Suzuki
authors: Stephen P
authors: SP
authors: Hunt
authors: Anthony H
authors: AH
authors: Dickenson
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006358:Hot Temperature; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010812:Physical Stimulation / Q000379:methods; D020671:Posterior Horn Cells / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000172:deficiency* / Q000235:genetics
chemical_list: D018040:Receptors, Neurokinin-1