Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2016 Jan 16

PMID 26770021

Citations 4

Authors

Jun Ho Jang

Taick Sang Nam

Jaebeom Jun

Se Jung Jung

Dong-Wook Kim

Joong Woo Leem

Affiliations

Soon will be listed here.

Abstract

We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity.

Citing Articles

Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development.

Adil K, Remonde C, Gonzales E, Boo K, Kwon K, Kim D Biomol Ther (Seoul). 2022; 30(4):320-327.

PMID: 35135902 PMC: 9252881. DOI: 10.4062/biomolther.2021.194.

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.

Kocot-Kepska M, Zajaczkowska R, Mika J, Kopsky D, Wordliczek J, Dobrogowski J Pharmaceutics. 2021; 13(4).

PMID: 33810493 PMC: 8067282. DOI: 10.3390/pharmaceutics13040450.

Peripheral Mechanisms of Neuropathic Pain-the Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain.

Kocot-Kepska M, Zajaczkowska R, Mika J, Wordliczek J, Dobrogowski J, Przeklasa-Muszynska A Pharmaceuticals (Basel). 2021; 14(2).

PMID: 33498496 PMC: 7909513. DOI: 10.3390/ph14020077.

Comparative Behavioral Assessment of Lewis and Nude Rats after Peripheral Nerve Injury.

Alawadhi E, Chu T, Midha R Comp Med. 2020; 70(3):233-238.

PMID: 32384941 PMC: 7287384. DOI: 10.30802/AALAS-CM-19-000079.

References

Li D, Ren Y, Xu X, Zou X, Fang L, Lin Q . Sensitization of primary afferent nociceptors induced by intradermal capsaicin involves the peripheral release of calcitonin gene-related Peptide driven by dorsal root reflexes. J Pain. 2008; 9(12):1155-68. PMC: 2642671. DOI: 10.1016/j.jpain.2008.06.011. View

Li Z, Ji G, Neugebauer V . Mitochondrial reactive oxygen species are activated by mGluR5 through IP3 and activate ERK and PKA to increase excitability of amygdala neurons and pain behavior. J Neurosci. 2011; 31(3):1114-27. PMC: 3073477. DOI: 10.1523/JNEUROSCI.5387-10.2011. View

Jin Y, Takemura M, Furuyama A, Yonehara N . Peripheral glutamate receptors are required for hyperalgesia induced by capsaicin. Pain Res Treat. 2011; 2012:915706. PMC: 3199092. DOI: 10.1155/2012/915706. View

Richardson J, Vasko M . Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther. 2002; 302(3):839-45. DOI: 10.1124/jpet.102.032797. View

Wang Z, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E . A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther. 2004; 309(3):869-78. DOI: 10.1124/jpet.103.064154. View

Meyer R, Campbell J, Raja S . Antidromic nerve stimulation in monkey does not sensitize unmyelinated nociceptors to heat. Brain Res. 1988; 441(1-2):168-72. DOI: 10.1016/0006-8993(88)91395-9. View

Carlton S, Hargett G . Colocalization of metabotropic glutamate receptors in rat dorsal root ganglion cells. J Comp Neurol. 2007; 501(5):780-9. DOI: 10.1002/cne.21285. View

Ushida T, Tani T, Kawasaki M, Iwatsu O, Yamamoto H . Peripheral administration of an N-methyl-D-aspartate receptor antagonist (MK-801) changes dorsal horn neuronal responses in rats. Neurosci Lett. 1999; 260(2):89-92. DOI: 10.1016/s0304-3940(98)00968-9. View

DIXON W . Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol. 1980; 20:441-62. DOI: 10.1146/annurev.pa.20.040180.002301. View

10.

Chen H, Qu F, He X, Kang S, Liao D, Lu S . Differential roles of peripheral metabotropic glutamate receptors in bee venom-induced nociception and inflammation in conscious rats. J Pain. 2009; 11(4):321-9. DOI: 10.1016/j.jpain.2009.07.013. View

11.

Shim B, Kim D, Kim B, Nam T, Leem J, Chung J . Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy. Neuroscience. 2005; 132(1):193-201. DOI: 10.1016/j.neuroscience.2004.12.036. View

12.

Jung C, Lee S, Choi H, Lim E, Lee M, Yang G . Participation of peripheral group I and II metabotropic glutamate receptors in the development or maintenance of IL-1beta-induced mechanical allodynia in the orofacial area of conscious rats. Neurosci Lett. 2006; 409(3):173-8. DOI: 10.1016/j.neulet.2006.09.043. View

13.

Keeble J, Bodkin J, Liang L, Wodarski R, Davies M, Fernandes E . Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms. Pain. 2008; 141(1-2):135-42. DOI: 10.1016/j.pain.2008.10.025. View

14.

Chaplan S, Bach F, Pogrel J, Chung J, Yaksh T . Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994; 53(1):55-63. DOI: 10.1016/0165-0270(94)90144-9. View

15.

Petrus M, Peier A, Bandell M, Hwang S, Huynh T, Olney N . A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain. 2007; 3:40. PMC: 2222610. DOI: 10.1186/1744-8069-3-40. View

16.

Mikami N, Matsushita H, Kato T, Kawasaki R, Sawazaki T, Kishimoto T . Calcitonin gene-related peptide is an important regulator of cutaneous immunity: effect on dendritic cell and T cell functions. J Immunol. 2011; 186(12):6886-93. DOI: 10.4049/jimmunol.1100028. View

17.

Bhave G, Karim F, Carlton S, Gereau 4th R . Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci. 2001; 4(4):417-23. DOI: 10.1038/86075. View

18.

Coggeshall R, Carlton S . Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and myelinated axons in the periphery. J Comp Neurol. 1998; 391(1):78-86. DOI: 10.1002/(sici)1096-9861(19980202)391:1<78::aid-cne7>3.3.co;2-8. View

19.

Gabra B, Kessler F, Ritter J, Dewey W, Smith F . Decrease in N-methyl-D-aspartic acid receptor-NR2B subunit levels by intrathecal short-hairpin RNA blocks group I metabotropic glutamate receptor-mediated hyperalgesia. J Pharmacol Exp Ther. 2007; 322(1):186-94. DOI: 10.1124/jpet.107.120071. View

20.

Davidson E, Coggeshall R, Carlton S . Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport. 1997; 8(4):941-6. DOI: 10.1097/00001756-199703030-00025. View