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

Author(s)

Manuel Munoz-Lora, Victor Ricardo ; Okrosa, Ana Dugonjic ; Matak, Ivica ; Del Bel Cury, Altair Antoninha ; Kalinichev, Mikhail ; Lackovic, Zdravko

• Document type: Journal article
• Source: TOXINS; v. 14, n. 3, p. 17-pg., 2022-03-01.

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. (AU)

• FAPESP's process: 18/13575-5 - Involvement of the glial cells in the antinociceptive effect of Botulinum toxin type A
• Grantee: Victor Ricardo Manuel Muñoz Lora
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 17/07741-7 - EFFECTS OF BONT-A PERIPHERAL-APPLICATION ON CENTRAL SENSITIZATION IN TMJ OF RATS
• Grantee: Victor Ricardo Manuel Muñoz Lora
• Support Opportunities: Scholarships in Brazil - Doctorate