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Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain
Open AccessArticle

Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury

Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 1945; https://doi.org/10.3390/ijms21061945
Received: 27 January 2020 / Revised: 9 March 2020 / Accepted: 10 March 2020 / Published: 12 March 2020
(This article belongs to the Special Issue Orofacial Pain: Molecular Mechanisms, Diagnosis and Treatment)
While the descending dopaminergic control system is not fully understood, it is reported that the hypothalamic A11 nucleus is its principle source. To better understand the impact of this system, particularly the A11 nucleus, on neuropathic pain, we created a chronic constriction injury model of the infraorbital nerve (ION-CCI) in rats. ION-CCI rats received intraperitoneal administrations of quinpirole (a dopamine D2 receptor agonist). ION-CCI rats received microinjections of quinpirole, muscimol [a gamma-aminobutyric acid type A (GABAA) receptor agonist], or neurotoxin 6-hydroxydopamine (6-OHDA) into the A11 nucleus. A von Frey filament was used as a mechanical stimulus on the maxillary whisker pad skin; behavioral and immunohistochemical responses to the stimulation were assessed. After intraperitoneal administration of quinpirole and microinjection of quinpirole or muscimol, ION-CCI rats showed an increase in head-withdrawal thresholds and a decrease in the number of phosphorylated extracellular signal-regulated kinase (pERK) immunoreactive (pERK-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Following 6-OHDA microinjection, ION-CCI rats showed a decrease in head-withdrawal thresholds and an increase in the number of pERK-IR cells in the Vc. Our findings suggest the descending dopaminergic control system is involved in the modulation of trigeminal neuropathic pain. View Full-Text
Keywords: chronic constriction injury; infraorbital nerve; A11 nucleus; dopamine receptor; quinpirole; muscimol; 6-hydroxydopamine; phosphorylated extracellular signal-regulated kinase (pERK); trigeminal spinal subnucleus caudalis chronic constriction injury; infraorbital nerve; A11 nucleus; dopamine receptor; quinpirole; muscimol; 6-hydroxydopamine; phosphorylated extracellular signal-regulated kinase (pERK); trigeminal spinal subnucleus caudalis
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Maegawa, H.; Usami, N.; Kudo, C.; Hanamoto, H.; Niwa, H. Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury. Int. J. Mol. Sci. 2020, 21, 1945.

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