The Journal of Neuroscience, February 1, 2001, 21(3):1039-1046
The NK1 Receptor Is Essential for the Full Expression of Noxious
Inhibitory Controls in the Mouse
Hervé
Bester1,
Carmen
De Felipe2, and
Stephen P.
Hunt1
1 Department of Anatomy and Developmental Biology,
University College London, London WC1E 6BT, United Kingdom, and
2 Instituto de Neurociencias, Universidad Miguel
Hernández, 03550 San Juan, Alicante, Spain
Behavioral analysis of the NK1 receptor gene knock-out (NK1
/)
mouse indicated that substance P was closely involved in orchestrating the physiological and behavioral response of the animal to major environmental stressors. In particular, endogenous pain control mechanisms, such as stress-induced analgesia were substantially impaired in mutant mice, suggesting a reduction in descending inhibitory controls to the spinal cord from the brainstem. To directly
test the integrity of descending controls in NK1/ mice, we have
analyzed c-Fos expression in laminae I-II of the lumbar and cervical
cord and in the rostral ventromedial medulla in an experimental
paradigm known to require recruitment of descending inhibitory
controls. Anesthetized mice were stimulated with water at 50°C either
on their forepaw, hindpaw, or on both the hindpaw plus forepaw
concurrently. Wild-type mice, naïve or treated with an NK1
antagonist (RP67580) or its inactive isomer (RP68651), were compared
with NK1/ mice. C-Fos expression at the lumbar laminae I-II level
was significantly reduced, whereas it was significantly greater in the
raphe magnus and pallidus nuclei in the double stimulation situation in
wild-type compared with NK1/ mice. Blocking the NK1 receptor
pharmacologically reproduced, in an enantiomere-selective manner, the
data from NK1/ mice, with no evidence for recruitment of descending
inhibition at the lumbar cord level after forepaw stimulation. The
present study demonstrates that the NK1 receptor is essential for the
full development of noxiously evoked descending inhibition.
Key words:
NK1 receptor; DNIC; laminae I-II; c-Fos; nociception; knock-out
Copyright © 2001 Society for Neuroscience 0270-6474/01/2131039-08$05.00/0
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