Antinociceptive Actions of Botulinum Toxin A1 on Immunogenic Hypersensitivity in Temporomandibular Joint of Rats.

Victor Ricardo Manuel Muñoz-Lora,Altair Antoninha Del Bel Cury,Ivica Matak,Mikhail Kalinichev,Ana Dugonjić Okroša,Zdravko Lacković

doi:10.3390/toxins14030161

Victor Ricardo Manuel Muñoz-Lora, Altair Antoninha Del Bel Cury + Show 4 more

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https://doi.org/10.3390/toxins14030161

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Abstract

Botulinum neurotoxin type A1 (BoNT-A) reduces the peripheral peptide and cytokine upregulation in rats with antigen-evoked persistent immunogenic hypersensitivity (PIH) of the temporomandibular joint (TMJ). Herein, we examined the effects of two preparations of BoNT-A, abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox), on spontaneous and evoked nociceptive behaviors, as well as on central neuronal and astroglial activation. The antigen-evoked PIH was induced in rats via repeated systemic and unilateral intra-articular (i.a.) injections of methylated bovine serum albumin (mBSA). Rats were subsequently injected with unilateral i.a. aboBoNT-A (14 U/kg), onaBoNT-A (7 U/kg), or the vehicle (saline). After i.a. treatments, spontaneous and mechanically evoked nocifensive behaviors were assessed before and after the low-dose i.a. formalin (0.5%) challenge. The central effects of BoNT-A were assessed by an immunohistochemical analysis of cleaved synaptosomal-associated protein 25 (cSNAP-25) presence, c-Fos, GFAP, and CGRP expression in the trigeminal nucleus caudalis (TNC). Both BoNT-A preparations similarly reduced the formalin-induced spontaneous pain-related behaviors and mechanical allodynia of the hypernociceptive rats. Likewise, their effects were associated with the central occurrence of cSNAP-25 and reduction of c-Fos and GFAP upregulation in the TNC. BoNT-A antinociceptive activity on the PIH is associated with the toxin axonal transport to trigeminal sensory areas and reduction of neuronal and glial activation in central nociceptive regions.

Highlights

Temporomandibular joint (TMJ) rheumatoid arthritis (RA) is a chronic inflammatory condition involving a range of local and systemic proinflammatory mediators
We extended the measurement of spontaneous nociception by examining facial grimacing related to pain (RGS) and examined if the spontaneous nociceptive responses are present both before and after temporomandibular joint (TMJ) stimulation with low-dose formalin 0.5%)
We further examined the possible Botulinum neurotoxin type A1 (BoNT-A) effects on neuronal and astrocyte activation associated with nociception in the trigeminal nucleus caudalis (TNC), the first-order pain processing sensory nucleus of the cranial area

Summary

Introduction

Temporomandibular joint (TMJ) rheumatoid arthritis (RA) is a chronic inflammatory condition involving a range of local and systemic proinflammatory mediators. TMJ-related symptoms are present in almost 65% of RA patients and are typically bilateral [2,3]. Along with the impairment of normal functions of the jaw joint, the TMJ-RA. Toxins 2022, 14, 161 typically bilateral [2,3]. Along with the impairment of normal functions of the jaw joint, the TMJ-RA is often associated with periods of alternating nonpainful and painful phases isActive often associated withare periods of provoked alternatingbynonpainful andnonpainful painful phases [1]. Painful phases usually an otherwise stimulus painful phases are usually provoked by an otherwise nonpainful stimulus (e.g., mandibular mandibular functional movements: speaking, eating, etc.), with a negative impact on the functional movements: speaking, eating, etc.), with a negative impact on the patient’s patient’s quality of life [4,5].

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