Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice.
BACKGROUND
The neurokinin-1 receptor and its primary ligand, substance P, are widely recognized as contributing to the spinal processing of nociceptive stimuli, yet the specific function of the neurokinin-1 receptor remains unclear.


METHODS
To better clarify these functions, the authors examined the neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In addition, the capacity of knockout and wild-type mice to show wind-up to repeated C-fiber stimuli and to show sensitization after cutaneous mustard oil was assessed.


RESULTS
A total of 68 nociceptive neurons (35 in knockout, 33 in wild type) in laminae III-V were studied. No differences in the acute responses of neurons in knockout and wild-type mice to graded mechanical, thermal, or electrical stimuli or in the acute responses to mustard oil were observed. However, wind-up to repeated electrical stimulation at C-fiber intensity was significantly attenuated in the knockout mice compared with wild type controls. In addition, mustard oil-induced mechanical hypersensitivity was significantly reduced in the knockout mice.


CONCLUSIONS
These results indicate that neurokinin-1 receptors do not play a significant role in the responses of nociceptive neurons in the deep spinal dorsal horn to acute noxious mechanical, thermal, electrical, or chemical stimuli. On the other hand, neurokinin-1 receptors are critical for the central hyperexcitability that is observed in these neurons with repeated C-fiber inputs and to the central sensitization induced by topical mustard oil application.
Weng
H R
HR
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mansikka
H
H
Winchurch
R
R
Raja
S N
SN
Dougherty
P M
PM
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008839:Microelectrodes; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000502:physiology*; D012677:Sensation / Q000502:physiology*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000166:cytology; D013268:Stimulation, Chemical
D018040:Receptors, Neurokinin-1