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Open Access Open Badges Commentary

Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P

Long-Jun Wu, Hui Xu, Shanelle W Ko, Megumu Yoshimura and Min Zhuo*

Author Affiliations

Department of Physiology, Faculty of Medicine, University of Toronto, University of Toronto Centre for the Study of Pain, Medical Science Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada

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Molecular Pain 2005, 1:34  doi:10.1186/1744-8069-1-34

Published: 18 November 2005


Substance P (SP) is a neuropeptide well known for its contribution to pain transmission in the spinal cord, however, less is known about the possible modulatory effects of SP. A new study by Gu and colleagues, published in Molecular Pain (2005, 1:20), describes its potential role in feed-forward inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition seems to function through a direct excitation of GABAergic interneurons by substance P released from primary afferent fibers and has a distinct temporal phase of action from the well-described glutamate-dependent feed-forward inhibition. It is believed that through this inhibition, substance P can balance nociceptive output from the spinal cord.