Zerumbone Modulates α2A-Adrenergic, TRPV1, and NMDA NR2B Receptors Plasticity in CCI-Induced Neuropathic Pain In Vivo and LPS-Induced SH-SY5Y Neuroblastoma In Vitro Models

Abstract

the anti-allodynic and anti-hyperalgesic effects of zerumbone. b 1 -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 a 2Aadrenoceptor, while an up-regulation was observed of NMDA NR2B receptors. Expression of TRPV1 receptors however did not significantly change. The in vitro study, representing a peripheral model, demonstrated the reduction of both NMDA NR2B and TRPV1 receptors while significantly increasing a 2A -adrenoceptor expression in contrast to the brain samples. Our current findings suggest that the a 1 -, a 2 -, b 1 -and b 2 -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. Keywords: zerumbone, neuropathic pain, a 2A -adrenoceptor, TRPV1, NMDA NR2B, allodynia and hyperalgesia Chia et al. Zerumbone; a 2A -adrenergic, TRPV1 and NMDA NR2B Frontiers in Pharmacology | www.frontiersin.org March 2020 | Volume 11 | Article 92 Chia et al. Zerumbone; a 2A -adrenergic, TRPV1 and NMDA NR2B Frontiers in Pharmacology | www.frontiersin.org March 2020 | Volume 11 | Article 92 3

The Anti-Inflammatory and Antioxidant Effects of Sodium Propionate

“…Changes in paw volume were measured as previously described [31]. noxious stimulus produced by formalin injection, the rats were lightly anesthetized and 50 µL of 5% formalin solution was injected subcutaneously (s.c.) into the dorsal surface of the right hind paw with a 30-g needle.…”

“…MPO activity, an index of polymorphonuclear cell accumulation, was determined as previously described in the hind paw tissues of all experimental groups [31]. The rate of change in absorbance was measured spectrophotometrically at 650 nm.…”

“…Biopsies of hind paws were taken 6 h following CAR injection. Histology was performed as previously described [31]. The degree of paw damage was evaluated according on a six-point score: 0 = no inflammation, 1 = mild inflammation, 2 = mild/moderate inflammation, 3 = moderate inflammation, 4 = moderate/severe inflammation and 5 = severe inflammation.…”

Zerumbone-Induced Analgesia Modulated via Potassium Channels and Opioid Receptors in Chronic Constriction Injury-Induced Neuropathic Pain

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The Analgesic and Anxiolytic Activity of Resveratrol Mediated by Different Sub-Types of α-Adrenoceptors of Anterior Cingulate Cortex Following Neuropathic Pain in Male Rats

“…Additionally, Liang et al (2017) revealed that the intrathecal administration of dexmedetomidine attenuated mechanical allodynia and thermal hyperalgesia in the CCI model of the sciatic nerve in Sprague-Dawley rats (11). Similarly, Chia et al (2020) revealed that the administration of zerumbone (the main bioactive compound, a wild ginger plant species) have anti-allodynia and anti-hyperalgesia effects via activation of α-and β-adrenoceptors in the CCI-induced neuropathic pain mouse model (12). Therefore, it is suggested that α-adrenoceptors have an important role in the processing of pain information in the central nervous system.…”