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Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia.
J Neurosci. 2007 Oct 31; 27(44):12067-77.JN

Abstract

The neuropeptide substance P (SP) is expressed in unmyelinated primary sensory neurons and represents the best known "pain" neurotransmitter. It is generally believed that SP regulates pain transmission and sensitization by acting on neurokinin-1 receptor (NK-1), which is expressed in postsynaptic dorsal horn neurons. However, the expression and role of NK-1 in primary sensory neurons are not clearly characterized. Our data showed that NK-1 was expressed in both intact and dissociated dorsal root ganglion (DRG) neurons. In particular, NK-1 was mainly coexpressed with the capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1), a critical receptor for the generation of heat hyperalgesia. NK-1 agonist [Sar(9), Met(O2)(11)]-substance P (Sar-SP) significantly potentiated capsaicin-induced currents and increase of [Ca2+]i in dissociated DRG neurons. NK-1 antagonist blocked not only the potentiation of TRPV1 currents but also heat hyperalgesia induced by intraplantar Sar-SP. NK-1 antagonist also inhibited capsaicin-induced spontaneous pain, and this inhibition was enhanced after inflammation. To analyze intracellular cross talking of NK-1 and TRPV1, we examined downstream signal pathways of G-protein-coupled NK-1 activation. Sar-SP-induced potentiation of TRPV1 was blocked by inhibition of G-protein, PLCbeta (phospholipase C-beta), or PKC but not by inhibition of PKA (protein kinase A). In particular, PKCepsilon inhibitor completely blocked both Sar-SP-induced TRPV1 potentiation and heat hyperalgesia. Sar-SP also induced membrane translocation of PKCepsilon in a portion of small DRG neurons. These results reveal a novel mechanism of NK-1 in primary sensory neurons via a possible autocrine and paracrine action of SP. Activation of NK-1 in these neurons induces heat hyperalgesia via PKCepsilon-mediated potentiation of TRPV1.

Authors+Show Affiliations

Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17978048

Citation

Zhang, Hua, et al. "Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons Via PKCepsilon: a Novel Pathway for Heat Hyperalgesia." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 27, no. 44, 2007, pp. 12067-77.
Zhang H, Cang CL, Kawasaki Y, et al. Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. J Neurosci. 2007;27(44):12067-77.
Zhang, H., Cang, C. L., Kawasaki, Y., Liang, L. L., Zhang, Y. Q., Ji, R. R., & Zhao, Z. Q. (2007). Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 27(44), 12067-77.
Zhang H, et al. Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons Via PKCepsilon: a Novel Pathway for Heat Hyperalgesia. J Neurosci. 2007 Oct 31;27(44):12067-77. PubMed PMID: 17978048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. AU - Zhang,Hua, AU - Cang,Chun-Lei, AU - Kawasaki,Yasuhiko, AU - Liang,Ling-Li, AU - Zhang,Yu-Qiu, AU - Ji,Ru-Rong, AU - Zhao,Zhi-Qi, PY - 2007/11/6/pubmed PY - 2007/12/6/medline PY - 2007/11/6/entrez SP - 12067 EP - 77 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 27 IS - 44 N2 - The neuropeptide substance P (SP) is expressed in unmyelinated primary sensory neurons and represents the best known "pain" neurotransmitter. It is generally believed that SP regulates pain transmission and sensitization by acting on neurokinin-1 receptor (NK-1), which is expressed in postsynaptic dorsal horn neurons. However, the expression and role of NK-1 in primary sensory neurons are not clearly characterized. Our data showed that NK-1 was expressed in both intact and dissociated dorsal root ganglion (DRG) neurons. In particular, NK-1 was mainly coexpressed with the capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1), a critical receptor for the generation of heat hyperalgesia. NK-1 agonist [Sar(9), Met(O2)(11)]-substance P (Sar-SP) significantly potentiated capsaicin-induced currents and increase of [Ca2+]i in dissociated DRG neurons. NK-1 antagonist blocked not only the potentiation of TRPV1 currents but also heat hyperalgesia induced by intraplantar Sar-SP. NK-1 antagonist also inhibited capsaicin-induced spontaneous pain, and this inhibition was enhanced after inflammation. To analyze intracellular cross talking of NK-1 and TRPV1, we examined downstream signal pathways of G-protein-coupled NK-1 activation. Sar-SP-induced potentiation of TRPV1 was blocked by inhibition of G-protein, PLCbeta (phospholipase C-beta), or PKC but not by inhibition of PKA (protein kinase A). In particular, PKCepsilon inhibitor completely blocked both Sar-SP-induced TRPV1 potentiation and heat hyperalgesia. Sar-SP also induced membrane translocation of PKCepsilon in a portion of small DRG neurons. These results reveal a novel mechanism of NK-1 in primary sensory neurons via a possible autocrine and paracrine action of SP. Activation of NK-1 in these neurons induces heat hyperalgesia via PKCepsilon-mediated potentiation of TRPV1. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/17978048/Neurokinin_1_receptor_enhances_TRPV1_activity_in_primary_sensory_neurons_via_PKCepsilon:_a_novel_pathway_for_heat_hyperalgesia_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=17978048 DB - PRIME DP - Unbound Medicine ER -