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Zerumbone Modulates α-Adrenergic, TRPV1, and NMDA NR2B Receptors Plasticity in CCI-Induced Neuropathic Pain and LPS-Induced SH-SY5Y Neuroblastoma Models

Overview
Journal Front Pharmacol
Date 2020 Mar 21
PMID 32194397
Citations 8
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Abstract

Zerumbone has shown great potential in various pathophysiological models of diseases, particularly in neuropathic pain conditions. Further understanding the mechanisms of action is important to develop zerumbone as a potential anti-nociceptive agent. Numerous receptors and pathways function to inhibit and modulate transmission of pain signals. Previously, we demonstrated involvement of the serotonergic system in zerumbone's anti-neuropathic effects. The present study was conducted to determine zerumbone's modulatory potential involving noradrenergic, transient receptor potential vanilloid type 1 (TRPV1) and -methyl-D-aspartate (NMDA) receptors in chronic constriction injury (CCI)-induced and lipopolysaccharide (LPS)-induced SH-SY5Y neuroinflammatory models. von Frey filament and Hargreaves plantar tests were used to assess allodynia and hyperalgesia in the chronic constriction injury-induced neuropathic pain mouse model. Involvement of specific adrenoceptors were investigated using antagonists- prazosin (α-adrenoceptor antagonist), idazoxan (α-adrenoceptor antagonist), metoprolol (β-adrenoceptor antagonist), ICI 118,551 (β-adrenoceptor antagonist), and SR 59230 A (β-adrenoceptor antagonist), co-administered with zerumbone (10 mg/kg). Involvement of excitatory receptors; TRPV and NMDA were conducted using antagonists capsazepine (TRPV1 antagonist) and memantine (NMDA antagonist). Western blot was conducted to investigate the effect of zerumbone on the expression of α-adrenoceptor, TRPV1 and NMDA NR2B receptors in CCI-induced whole brain samples of mice as well as in LPS-induced SH-SY5Y neuroblastoma cells. Pre-treatment with α- and α-adrenoceptor antagonists significantly attenuated both anti-allodynic and anti-hyperalgesic effects of zerumbone. For β-adrenoceptors, only β-adrenoceptor antagonist significantly reversed the anti-allodynic and anti-hyperalgesic effects of zerumbone. β-adrenoceptor antagonist only reversed the anti-allodynic effect of zerumbone. The anti-allodynic and anti-hyperalgesic effects of zerumbone were both absent when TRPV1 and NMDA receptors were antagonized in both nociceptive assays. Zerumbone treatment markedly decreased the expression of α-adrenoceptor, while an up-regulation was observed of NMDA NR2B receptors. Expression of TRPV1 receptors however did not significantly change. The study, representing a peripheral model, demonstrated the reduction of both NMDA NR2B and TRPV1 receptors while significantly increasing α-adrenoceptor expression in contrast to the brain samples. Our current findings suggest that the α-, α-, β- and β-adrenoceptors, TRPV1 and NMDA NR2B are essential for the anti-allodynic and antihyperalgesic effects of zerumbone. Alternatively, we demonstrated the plasticity of these receptors through their response to zerumbone's administration.

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References
1.
Millan M . Descending control of pain. Prog Neurobiol. 2002; 66(6):355-474. DOI: 10.1016/s0301-0082(02)00009-6. View

2.
Rosin D, Zeng D, Stornetta R, Norton F, Riley T, Okusa M . Immunohistochemical localization of alpha 2A-adrenergic receptors in catecholaminergic and other brainstem neurons in the rat. Neuroscience. 1993; 56(1):139-55. DOI: 10.1016/0306-4522(93)90569-2. View

3.
Anand P, Bley K . Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011; 107(4):490-502. PMC: 3169333. DOI: 10.1093/bja/aer260. View

4.
Kimura M, Saito S, Obata H . Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord. Neurosci Lett. 2012; 529(1):70-4. DOI: 10.1016/j.neulet.2012.08.008. View

5.
Howe J, Wang J, Yaksh T . Selective antagonism of the antinociceptive effect of intrathecally applied alpha adrenergic agonists by intrathecal prazosin and intrathecal yohimbine. J Pharmacol Exp Ther. 1983; 224(3):552-8. View