Increased Neuronal Expression of Neurokinin-1 Receptor and Stimulus-evoked Internalization of the Receptor in the Rostral Ventromedial Medulla of the Rat After Peripheral Inflammatory Injury

Overview

Journal J Comp Neurol

Specialty Neurology

Date 2014 Mar 19

PMID 24639151

Citations 4

Authors

Marta V Hamity

Roxanne Y Walder

Donna L Hammond

Affiliations

Soon will be listed here.

Abstract

This study examined possible mechanisms by which Substance P (Sub P) assumes a pronociceptive role in the rostral ventromedial medulla (RVM) under conditions of peripheral inflammatory injury, in this case produced by intraplantar (ipl) injection of complete Freund's adjuvant (CFA). In saline- and CFA-treated rats, neurokinin-1 receptor (NK1R) immunoreactivity was localized to neurons in the RVM. Four days after ipl injection of CFA, the number of NK1R-immunoreactive neurons in the RVM was increased by 30%, and there was a concomitant increase in NK1R-immunoreactive processes in CFA-treated rats. Although NK1R immunoreactivity was increased, tachykinin-1 receptor (Tacr1) mRNA was not increased in the RVM of CFA-treated rats. To assess changes in Sub P release, the number of RVM neurons that exhibited NK1R internalization was examined in saline- and CFA-treated rats following noxious heat stimulation of the hind paws. Only CFA-treated rats that experienced noxious heat stimulation exhibited a significant increase in the number of neurons showing NK1R internalization. These data suggest that tonic Sub P release is not increased as a simple consequence of peripheral inflammation, but that phasic or evoked release of Sub P in the RVM is increased in response to noxious peripheral stimulation in a persistent inflammatory state. These data support the proposal that an upregulation of the NK1R in the RVM, as well as enhanced release of Sub P following noxious stimulation, underlie the pronociceptive role of Sub P under conditions of persistent inflammatory injury.

Citing Articles

Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala.

Khom S, Steinkellner T, Hnasko T, Roberto M Sci Adv. 2020; 6(12):eaaz1050.

PMID: 32206720 PMC: 7080445. DOI: 10.1126/sciadv.aaz1050.

Plasticity in Brainstem Mechanisms of Pain Modulation by Nicotinic Acetylcholine Receptors in the Rat.

Jareczek F, White S, Hammond D eNeuro. 2017; 4(1).

PMID: 28197544 PMC: 5286660. DOI: 10.1523/ENEURO.0364-16.2017.

Changes in the disposition of substance P in the rostral ventromedial medulla after inflammatory injury in the rat.

Maduka U, Hamity M, Walder R, White S, Li Y, Hammond D Neuroscience. 2016; 317:1-11.

PMID: 26762802 PMC: 4738059. DOI: 10.1016/j.neuroscience.2015.12.054.

Validation of four reference genes for quantitative mRNA expression studies in a rat model of inflammatory injury.

Walder R, Wattiez A, White S, Marquez De Prado B, Hamity M, Hammond D Mol Pain. 2014; 10:55.

PMID: 25187167 PMC: 4161874. DOI: 10.1186/1744-8069-10-55.

References

Sandkuhler J, Benrath J, Brechtel C, Ruscheweyh R, Heinke B . Synaptic mechanisms of hyperalgesia. Prog Brain Res. 2000; 129:81-100. DOI: 10.1016/S0079-6123(00)29007-9. View

Ptak K, Burnet H, Blanchi B, Sieweke M, de Felipe C, Hunt S . The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation. Eur J Neurosci. 2002; 16(12):2245-52. DOI: 10.1046/j.1460-9568.2002.02305.x. View

Wei F, Guo W, Zou S, Ren K, Dubner R . Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J Neurosci. 2008; 28(42):10482-95. PMC: 2660868. DOI: 10.1523/JNEUROSCI.3593-08.2008. View

Vogel C, Marcotte E . Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012; 13(4):227-32. PMC: 3654667. DOI: 10.1038/nrg3185. View

Marriott D, Wilkin G . Substance P receptors on O-2A progenitor cells and type-2 astrocytes in vitro. J Neurochem. 1993; 61(3):826-34. DOI: 10.1111/j.1471-4159.1993.tb03593.x. View

Honor P, Menning P, Rogers S, Nichols M, Basbaum A, Besson J . Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states. J Neurosci. 1999; 19(17):7670-8. PMC: 6782496. View

Miki K, Guo W, Guan Y, Terayama R, Dubner R, Ren K . Changes in gene expression and neuronal phenotype in brain stem pain modulatory circuitry after inflammation. J Neurophysiol. 2002; 87(2):750-60. DOI: 10.1152/jn.00534.2001. View

Nakaya Y, Kaneko T, Shigemoto R, Nakanishi S, Mizuno N . Immunohistochemical localization of substance P receptor in the central nervous system of the adult rat. J Comp Neurol. 1994; 347(2):249-74. DOI: 10.1002/cne.903470208. View

Abbadie C, Trafton J, Liu H, Mantyh P, Basbaum A . Inflammation increases the distribution of dorsal horn neurons that internalize the neurokinin-1 receptor in response to noxious and non-noxious stimulation. J Neurosci. 1997; 17(20):8049-60. PMC: 6793895. View

10.

Budai D, Khasabov S, Mantyh P, Simone D . NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla. J Neurophysiol. 2006; 97(2):1388-95. DOI: 10.1152/jn.00450.2006. View

11.

Pacharinsak C, Khasabov S, Beitz A, Simone D . NK-1 receptors in the rostral ventromedial medulla contribute to hyperalgesia produced by intraplantar injection of capsaicin. Pain. 2008; 139(1):34-46. DOI: 10.1016/j.pain.2008.02.032. View

12.

Lagraize S, Guo W, Yang K, Wei F, Ren K, Dubner R . Spinal cord mechanisms mediating behavioral hyperalgesia induced by neurokinin-1 tachykinin receptor activation in the rostral ventromedial medulla. Neuroscience. 2010; 171(4):1341-56. PMC: 3006078. DOI: 10.1016/j.neuroscience.2010.09.040. View

13.

Mullen R, Buck C, Smith A . NeuN, a neuronal specific nuclear protein in vertebrates. Development. 1992; 116(1):201-11. DOI: 10.1242/dev.116.1.201. View

14.

Heng Y, Saunders C, Kunde D, Geraghty D . TRPV1, NK1 receptor and substance P immunoreactivity and gene expression in the rat lumbosacral spinal cord and urinary bladder after systemic, low dose vanilloid administration. Regul Pept. 2011; 167(2-3):250-8. DOI: 10.1016/j.regpep.2011.02.004. View

15.

Pinto M, Sousa M, Lima D, Tavares I . Participation of mu-opioid, GABA(B), and NK1 receptors of major pain control medullary areas in pathways targeting the rat spinal cord: implications for descending modulation of nociceptive transmission. J Comp Neurol. 2008; 510(2):175-87. DOI: 10.1002/cne.21793. View

16.

Coggeshall R, Lekan H . Methods for determining numbers of cells and synapses: a case for more uniform standards of review. J Comp Neurol. 1996; 364(1):6-15. DOI: 10.1002/(SICI)1096-9861(19960101)364:1<6::AID-CNE2>3.0.CO;2-9. View

17.

Ren K, Dubner R . Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008; 21(5):570-9. PMC: 2735048. DOI: 10.1097/ACO.0b013e32830edbdf. View

18.

Guo W, Robbins M, Wei F, Zou S, Dubner R, Ren K . Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci. 2006; 26(1):126-37. PMC: 6674294. DOI: 10.1523/JNEUROSCI.3686-05.2006. View

19.

Almarestani L, Waters S, Krause J, Bennett G, Ribeiro-da-Silva A . De novo expression of the neurokinin 1 receptor in spinal lamina I pyramidal neurons in polyarthritis. J Comp Neurol. 2009; 514(3):284-95. DOI: 10.1002/cne.22024. View

20.

Guo W, Wang H, Watanabe M, Shimizu K, Zou S, Lagraize S . Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci. 2007; 27(22):6006-18. PMC: 2676443. DOI: 10.1523/JNEUROSCI.0176-07.2007. View