scholarly journals Inhibition of the Nav1.7 Channel in the Trigeminal Ganglion Relieves Pulpitis Inflammatory Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjee Kwon ◽  
Il Young Jung ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee

Pulpitis causes significant changes in the peripheral nervous system, which induce hyperalgesia. However, the relationship between neuronal activity and Nav1.7 expression following pulpal noxious pain has not yet been investigated in the trigeminal ganglion (TG). The aim of our study was to verify whether experimentally induced pulpitis activates the expression of Nav1.7 peripherally and the neuronal activities of the TGs can be affected by Nav1.7 channel inhibition. Acute pulpitis was induced through allyl isothiocyanate (AITC) application to the rat maxillary molar tooth pulp. Three days after AITC application, abnormal pain behaviors were recorded, and the rats were euthanized to allow for immunohistochemical, optical imaging, and western blot analyses of the Nav1.7 expression in the TG. A significant increase in AITC-induced pain-like behaviors and histological evidence of pulpitis were observed. In addition, histological and western blot data showed that Nav1.7 expressions in the TGs were significantly higher in the AITC group than in the naive and saline group rats. Optical imaging showed that the AITC group showed higher neuronal activity after electrical stimulation of the TGs. Additionally, treatment of ProTxII, selective Nav1.7 blocker, on to the TGs in the AITC group effectively suppressed the hyperpolarized activity after electrical stimulation. These findings indicate that the inhibition of the Nav1.7 channel could modulate nociceptive signal processing in the TG following pulp inflammation.

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Kohei Kanno ◽  
Kohei Shimizu ◽  
Masamichi Shinoda ◽  
Makoto Hayashi ◽  
Osamu Takeichi ◽  
...  

Abstract Background The existence of referred pain and ectopic paresthesia caused by tooth pulp inflammation may make definitive diagnosis difficult and cause misdiagnosis or mistreatment; thus, elucidation of that molecular mechanism is urgent. In the present study, we investigated the mechanisms underlying ectopic pain, especially tongue hyperalgesia, after tooth pulp inflammation. Methods A rat model with mandibular first molar tooth pulp exposure was employed. Tooth pulp exposure-induced heat and mechanical-evoked tongue hypersensitivity was measured, and immunohistochemical staining for Iba1, a marker of active macrophages, IL-1β, IL-1 type I receptor (IL-1RΙ), and toll-like receptor 4 in the trigeminal ganglion was performed. In addition, we investigated the effects of injections of liposomal clodronate Clophosome-A (LCCA), a selective macrophage depletion agent, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS, a toll-like receptor 4 antagonist), IL-1β, or heat shock protein 70 (Hsp70, a selective agonist of toll-like receptor 4), to examine changes in tongue hypersensitivity and in the regulation of IL-1RΙ, toll-like receptor 4, and transient receptor potential vanilloid 1 (TRPV1) biosynthesis. Results At day 1 after tooth pulp exposure, obvious tooth pulp inflammation was observed. Tooth pulp exposure-induced heat and mechanical tongue hypersensitivity was observed from days 1 to 3 after tooth pulp exposure. The production of IL-1β in activated macrophages and toll-like receptor 4 and IL-1RΙ expression were significantly increased in trigeminal ganglion neurons innervating the tongue following tooth pulp exposure. Intra-trigeminal ganglion injection of LCCA significantly suppressed tongue hypersensitivity; however, toll-like receptor 4 and IL-1RΙ expression in trigeminal ganglion neurons innervating the tongue was not significantly altered. Intra-trigeminal ganglion injection of LPS-RS significantly suppressed tongue hypersensitivity and reduced IL-1RΙ expression in the trigeminal ganglion neurons innervating the tongue following tooth pulp exposure. Intra-trigeminal ganglion injection of recombinant Hsp70 significantly promoted tongue hypersensitivity and increased IL-1RI expression in trigeminal ganglion neurons innervating the tongue in naive rats. Furthermore, intra-trigeminal ganglion injection of recombinant IL-1β led to tongue hypersensitivity and enhanced TRPV1 expression in trigeminal ganglion neurons innervating the tongue in naive rats. Conclusions The present findings suggest that the neuron-macrophage interaction mediated by toll-like receptor 4 and IL-1RI activation in trigeminal ganglion neurons affects the pathogenesis of abnormal tongue pain following tooth pulp inflammation via IL-1RI and TRPV1 signaling in the trigeminal ganglion. Further research may contribute to the establishment of new therapeutic and diagnostic methods.


2016 ◽  
Vol 633 ◽  
pp. 240-245 ◽  
Author(s):  
Qin Liu ◽  
Zhixiong Gao ◽  
Xiao Zhu ◽  
Zhi Wu ◽  
Dongpei Li ◽  
...  

1993 ◽  
Vol 18 ◽  
pp. S199
Author(s):  
Michio Sugitani ◽  
Tokio Sugai ◽  
Manabu Tanifuji ◽  
Kazuyuki Murase ◽  
Norihiko Onoda

Author(s):  
Sébastien Ballesta ◽  
Weikang Shi ◽  
Katherine E. Conen ◽  
Camillo Padoa-Schioppa

AbstractIt has long been hypothesized that economic choices rely on the assignment and comparison of subjective values. Indeed, when agents make decisions, neurons in orbitofrontal cortex encode the values of offered and chosen goods. Moreover, neuronal activity in this area suggests the formation of a decision. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking economic choices to value signals in the brain remains correlational. We address this fundamental issue using electrical stimulation in rhesus monkeys. We show that suitable currents bias choices by increasing the value of individual offers. Furthermore, high-current stimulation disrupts both the computation and the comparison of subjective values. These results demonstrate that values encoded in orbitofrontal cortex are causal to economic choices.


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