Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury.

Hiroharu Maegawa,Nayuka Usami,Hitoshi Niwa,Hiroshi Hanamoto,Chiho Kudo

doi:10.3390/ijms21061945

Hiroharu Maegawa, Nayuka Usami + Show 3 more

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https://doi.org/10.3390/ijms21061945

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Abstract

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.

Highlights

The modulation of nociceptive inputs from descending noradrenergic and serotonergic control systems is well documented [1,2,3,4]
We found that the systemic administration of a dopamine D2 receptor agonist attenuated the mechanical hypersensitivity induced by ION-CCI and decreased the number of phosphorylated extracellular signal-regulated kinase (pERK)-IR cells in the superficial layers of the Vc in rats with ION-CCI
Our findings indicate that systemic administration of a dopamine D2 receptor agonist suppresses mechanical hypersensitivity induced by ION-CCI

Summary

Introduction

The modulation of nociceptive inputs from descending noradrenergic and serotonergic control systems is well documented [1,2,3,4]. It is likely that the dopaminergic descending control system is involved in the processing of nociceptive stimuli [5,6]. Several studies showed that the dopaminergic system was related to antinociception [7,8,9]. Dopamine receptors are classified into two families: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors. The D2-like receptors mediate antinociception [6,10,11] and are the most prominent dopamine receptor subtype in the spinal dorsal horn (SDH) and medullary dorsal horn (MDH) [12,13,14]

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