Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2005 Nov 18:1:34.
doi: 10.1186/1744-8069-1-34.

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

Long-Jun Wu  1 , Hui Xu, Shanelle W Ko, Megumu Yoshimura, Min Zhuo
Affiliations
Review

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

Long-Jun Wu et al. Mol Pain. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic diagram of SP-driven feed-forward inhibition in lamina V of the spinal cord dorsal horn. Sensory information starts from dorsal root ganglion (DRG) neurons, is relayed by spinal cord dorsal horn neurons and then is projecting to the brain. The intense painful stimulation of primary afferent, mostly Aδ- and C- fibers, induced the release of SP in lamina I and V. On the one hand, SP directly excites projection neurons in laminar I, thereby inducing pronociceptive response. On the other hand, SP in laminar V excites inhibitory interneurons in lamina V, through NK1 receptor (NK1R) and the following signaling pathway involved pertussis toxin-sensitive Gi/Go protein and possible downstream _targets Ca2+ or K+ channels. The firing of these interneurons releases GABA and/or glycine, activate GABAA receptor (GABAAR) and/or glycine receptor (GlyR), and initiates feed-forward inhibition in the projection neurons ascending to the brain. The inhibitory interneuron is in green and the projection neuron is in red.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Li P, Zhuo M. Substance P and neurokinin A mediate sensory synaptic transmission in young rat dorsal horn neurons. Brain Res Bull. 2001;55:521–531. doi: 10.1016/S0361-9230(01)00553-6. - DOI - PubMed
    1. Yoshimura M, Jessell TM. Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro. J Neurophysiol. 1989;62:96–108. - PubMed
    1. De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, Laird JM, Belmonte C, Cervero F, Hunt SP. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature. 1998;392:394–397. doi: 10.1038/32904. - DOI - PubMed
    1. Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998;392:390–394. doi: 10.1038/32897. - DOI - PubMed
    1. Rupniak NM, Kramer MS. Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists. Trends Pharmacol Sci. 1999;20:485–490. doi: 10.1016/S0165-6147(99)01396-6. - DOI - PubMed
  NODES
INTERN 4
Project 4
twitter 2