Tsuboi Y, Honda K, Bae Y C, Shinoda M, Kondo M, Katagiri A, Echizenya S, Kamakura S, Lee J, Iwata K
Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
Eur J Pain. 2015 Oct;19(9):1258-66. doi: 10.1002/ejp.650. Epub 2014 Dec 19.
It is important to know the mechanisms underlying pain abnormalities associated with inferior alveolar nerve (IAN) regeneration in order to develop the appropriate treatment for orofacial neuropathic pain patients. However, peripheral mechanisms underlying orofacial pain abnormalities following IAN regeneration are not fully understood.
Head withdrawal threshold (HWT), jaw opening reflex (JOR) thresholds, single-fibre recordings of the regenerated mental nerve (MN) fibres, calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), peripherin, neurofilament-200 (NF-200) and transient receptor potential vanilloid 1 (TRPV1) expression in trigeminal ganglion (TG) cells, and electron microscopic (EM) observations of the regenerated MN fibres were studied in MN- and IAN-transected (M-IANX) rats.
HWT to mechanical or heat stimulation of the mental skin was significantly lower in M-IANX rats compared with sham rats. Mean conduction velocity of action potentials recorded from MN fibres (n = 124) was significantly slower in M-IANX rats compared with sham rats. The percentage of Fluoro-Gold (FG)-labelled CGRP-, peripherin- or TRPV1-immunoreactive (IR) cells was significantly larger in M-IANX rats compared with that of sham rats, whereas that of FG-labelled IB4- and NF-200-IR cells was significantly smaller in M-IANX rats compared with sham rats. Large-sized myelinated nerve fibres were rarely observed in M-IANX rats, whereas large-sized unmyelinated nerve fibres were frequently observed and were aggregated in the bundles at the distal portion of regenerated axons.
These findings suggest that the demyelination of MN fibres following regeneration may be involved in peripheral sensitization, resulting in the orofacial neuropathic pain associated with trigeminal nerve injury.
了解与下牙槽神经（IAN）再生相关的疼痛异常背后的机制，对于为口面部神经性疼痛患者制定合适的治疗方案至关重要。然而，IAN再生后口面部疼痛异常的外周机制尚未完全明确。
在切断颏神经（MN）和IAN（M-IANX）的大鼠中，研究了撤头阈值（HWT）、张口反射（JOR）阈值、再生颏神经（MN）纤维的单纤维记录、三叉神经节（TG）细胞中降钙素基因相关肽（CGRP）、异凝集素B4（IB4）、外周蛋白、神经丝200（NF-200）和瞬时受体电位香草酸亚型1（TRPV1）的表达，以及再生MN纤维的电子显微镜（EM）观察。
与假手术大鼠相比，M-IANX大鼠对颏部皮肤机械或热刺激的HWT显著降低。与假手术大鼠相比，M-IANX大鼠中从MN纤维记录的动作电位的平均传导速度显著减慢。与假手术大鼠相比，M-IANX大鼠中荧光金（FG）标记的CGRP、外周蛋白或TRPV1免疫反应性（IR）细胞的百分比显著增加，而M-IANX大鼠中FG标记的IB4和NF-200-IR细胞的百分比显著低于假手术大鼠。在M-IANX大鼠中很少观察到大型有髓神经纤维，而经常观察到大型无髓神经纤维，并且它们在再生轴突远端聚集在束中。
这些发现表明，再生后MN纤维的脱髓鞘可能参与外周敏化，导致与三叉神经损伤相关的口面部神经性疼痛。
