Neuropeptide Y Inhibits Capsaicin-sensitive Nociceptors Via a Y1-receptor-mediated Mechanism

Overview

Journal Neuroscience

Specialty Neurology

Date 2004 Apr 22

PMID 15099684

Citations 17

Authors

J Gibbs

C M Flores

K M Hargreaves

Affiliations

Soon will be listed here.

Abstract

Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu(31)Pro(34)]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC(50) value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors.

Citing Articles

Blockade of mesenteric and omental adipose tissue sensory neurons improves cardiac remodeling through sympathetic pathway.

Huang J, Liu X, Qiu Q, Tan W, Li R, Xi H iScience. 2024; 27(7):110245.

PMID: 39055939 PMC: 11269788. DOI: 10.1016/j.isci.2024.110245.

Mechanical and chemical itch regulated by neuropeptide Y-Y signaling.

Chen S, Chen J, Tang D, Yin W, Xu S, Gao P Mol Pain. 2024; 20:17448069241242982.

PMID: 38485252 PMC: 10981256. DOI: 10.1177/17448069241242982.

Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.

Morris A, Parker R, Nazzal M, Natoli R, Fehrenbacher J, Kacena M Curr Osteoporos Rep. 2024; 22(1):193-204.

PMID: 38236511 PMC: 10912155. DOI: 10.1007/s11914-023-00846-y.

Transcription factor mesenchyme homeobox protein 2 (MEOX2) modulates nociceptor function.

Kokotovic T, Lenartowicz E, Langeslag M, Ciotu C, Fell C, Scaramuzza A FEBS J. 2022; 289(12):3457-3476.

PMID: 35029322 PMC: 9306780. DOI: 10.1111/febs.16347.

Targeting spinal neuropeptide Y1 receptor-expressing interneurons to alleviate chronic pain and itch.

Nelson T, Taylor B Prog Neurobiol. 2020; 196:101894.

PMID: 32777329 PMC: 8088728. DOI: 10.1016/j.pneurobio.2020.101894.

References

Xu I, Hao J, Xu X, Hokfelt T, Wiesenfeld-Hallin Z . The effect of intrathecal selective agonists of Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal and axotomized rats. Brain Res. 1999; 833(2):251-7. DOI: 10.1016/s0006-8993(99)01551-6. View

Naveilhan P, Hassani H, Lucas G, Blakeman K, Hao J, Xu X . Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature. 2001; 409(6819):513-7. DOI: 10.1038/35054063. View

Nouel D, Dumont Y, Beaudet A, Quirion R . Association of neuropeptide Y Y1 receptors with glutamate-positive and NPY-positive neurons in rat hippocampal cultures. Eur J Neurosci. 2000; 12(4):1319-30. DOI: 10.1046/j.1460-9568.2000.00024.x. View

Ossipov M, Zhang E, Carvajal C, Gardell L, Quirion R, Dumont Y . Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. J Neurosci. 2002; 22(22):9858-67. PMC: 6757820. View

Balasubramaniam A . Neuropeptide Y family of hormones: receptor subtypes and antagonists. Peptides. 1997; 18(3):445-57. DOI: 10.1016/s0196-9781(96)00347-6. View

van Rossum D, Hanisch U, Quirion R . Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev. 1997; 21(5):649-78. DOI: 10.1016/s0149-7634(96)00023-1. View

Mark M, Jarrott B, Colvin L, MacMillan S, Duggan A . The release of immunoreactive neuropeptide Y in the spinal cord of the anaesthetized rat and cat. Brain Res. 1997; 754(1-2):195-203. DOI: 10.1016/s0006-8993(97)00061-9. View

Pohl M, Benoliel J, Bourgoin S, Lombard M, Mauborgne A, Taquet H . Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal.... J Neurochem. 1990; 55(4):1122-30. DOI: 10.1111/j.1471-4159.1990.tb03114.x. View

Mantyh P, Allen C, Rogers S, DeMaster E, Ghilardi J, Mosconi T . Some sensory neurons express neuropeptide Y receptors: potential paracrine inhibition of primary afferent nociceptors following peripheral nerve injury. J Neurosci. 1994; 14(6):3958-68. PMC: 6576933. View

10.

Zhang X, Shi T, Holmberg K, Landry M, Huang W, Xiao H . Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia. Proc Natl Acad Sci U S A. 1997; 94(2):729-34. PMC: 19582. DOI: 10.1073/pnas.94.2.729. View

11.

Ji R, Zhang X, Wiesenfeld-Hallin Z, Hokfelt T . Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation. J Neurosci. 1994; 14(11 Pt 1):6423-34. PMC: 6577270. View

12.

Van Liefde , Vanderheyden P, De Backer J, Ebinger G, Vauquelin G . Effects of BIBP3226 and BIBP3435 on cytosolic calcium in neuropeptide Y Y1 receptor-transfected Chinese hamster ovary cells and wild type CHO-K1 cells. J Recept Signal Transduct Res. 2001; 21(1):11-23. DOI: 10.1081/rrs-100107139. View

13.

Marchand J, Cepeda M, Carr D, Wurm W, Kream R . Alterations in neuropeptide Y, tyrosine hydroxylase, and Y-receptor subtype distribution following spinal nerve injury to rats. Pain. 1999; 79(2-3):187-200. DOI: 10.1016/s0304-3959(98)00165-1. View

14.

Morton C, Hutchison W . Release of sensory neuropeptides in the spinal cord: studies with calcitonin gene-related peptide and galanin. Neuroscience. 1989; 31(3):807-15. DOI: 10.1016/0306-4522(89)90443-0. View

15.

Wakisaka S, Kajander K, Bennett G . Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett. 1991; 124(2):200-3. DOI: 10.1016/0304-3940(91)90093-9. View

16.

Mollereau C, Gouarderes C, Dumont Y, Kotani M, Detheux M, Doods H . Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226. Br J Pharmacol. 2001; 133(1):1-4. PMC: 1572765. DOI: 10.1038/sj.bjp.0704049. View

17.

Zhang X, Bao L, Xu Z, Kopp J, Arvidsson U, Elde R . Localization of neuropeptide Y Y1 receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons. Proc Natl Acad Sci U S A. 1994; 91(24):11738-42. PMC: 45307. DOI: 10.1073/pnas.91.24.11738. View

18.

Kar S, Quirion R . Quantitative autoradiographic localization of [125I]neuropeptide Y receptor binding sites in rat spinal cord and the effects of neonatal capsaicin, dorsal rhizotomy and peripheral axotomy. Brain Res. 1992; 574(1-2):333-7. DOI: 10.1016/0006-8993(92)90836-x. View

19.

Garry M, Richardson J, Hargreaves K . Sodium nitroprusside evokes the release of immunoreactive calcitonin gene-related peptide and substance P from dorsal horn slices via nitric oxide-dependent and nitric oxide-independent mechanisms. J Neurosci. 1994; 14(7):4329-37. PMC: 6577028. View

20.

Trivedi P, Yu H, Trumbauer M, Chen H, Van der Ploeg L, Guan X . Differential regulation of neuropeptide Y receptors in the brains of NPY knock-out mice. Peptides. 2001; 22(3):395-403. DOI: 10.1016/s0196-9781(01)00349-7. View