Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord.
In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets.
McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA. nakatsuk@cc.saga-u.ac.jp
Terumasa
T
Nakatsuka
Meng
M
Chen
Daisuke
D
Takeda
Christopher
C
King
Jennifer
J
Ling
Hong
H
Xing
Toyofumi
T
Ataka
Charles
C
Vierck
Robert
R
Yezierski
Jianguo G
JG
Gu
D000818:Animals; D001522:Behavior, Animal; D025461:Feedback, Physiological / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism; D008322:Mammals / Q000502:physiology*; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*
D005971:Glutamates; D018040:Receptors, Neurokinin-1; D013373:Substance P