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.
Nakatsuka
Terumasa
T
McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA. nakatsuk@cc.saga-u.ac.jp
Chen
Meng
M
Takeda
Daisuke
D
King
Christopher
C
Ling
Jennifer
J
Xing
Hong
H
Ataka
Toyofumi
T
Vierck
Charles
C
Yezierski
Robert
R
Gu
Jianguo G
JG
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