RT Journal Article
SR Electronic
T1 The NK1 Receptor Is Essential for the Full Expression of Noxious Inhibitory Controls in the Mouse
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1039
OP 1046
DO 10.1523/JNEUROSCI.21-03-01039.2001
VO 21
IS 3
A1 Hervé Bester
A1 Carmen De Felipe
A1 Stephen P. Hunt
YR 2001
UL http://www.jneurosci.org/content/21/3/1039.abstract
AB 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, naı̈ve 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.