Avaliação do potencial terapêutico de diferentes marcas de neurotoxina botulínica em modelo murino de disfunção da articulação temporomandibular

Abstract

Orofacial pain is a painful condition associated with soft and hard tissues of the head, face, and neck. Among chronic orofacial pains is Temporomandibular Dysfunction (TMD), a disease affecting the temporomandibular joint (TMJ), facial/head muscles, and neck. Managing this condition is challenging because many affected individuals report not experiencing pain relief with traditional therapeutic approaches. For this reason, botulinum neurotoxin type A (NTBos-A) has emerged as a therapeutic option to treat these conditions. NTBos-A, known worldwide by the brand name Botox®, is a compound with various therapeutic uses, but only the Botox® brand has Food and Drug Administration (FDA) approval for the treatment of migraine. Despite the lack of formal approval, NTBos-A is used off-label to treat other orofacial pains, including TMD. In the market, we find different brands of NTBos-A: such as Botox®, Dysport®, and Xeomin®, used as if they were the same product, with dosages based on aesthetic applications. Given the importance of treating chronic orofacial pain and the therapeutic potential of NTBos-A, this research evaluated the analgesic effect of different NTBos-A formulations in an animal model of TMD. The animal model used was that of temporomandibular dysfunction induced by Freund's Complete Adjuvant (CFA). Male C57BL/6J mice, approximately 60 days old, were used, divided into 3 groups: Saline (control), CFA (model), CFA + botulinum neurotoxin (experimental). First, on day 0, the animals were anesthetized with 2% Isoflurane with O2 supplementation. A 20 µL injection of saline or CFA at a concentration of 1 µg/ml was administered into the temporomandibular joint. Animals subjected to this model (CFA) were treated on day 14, after the onset of pain, with NTBos-A from the brands Botox® (0.06U), Dysport® (0.02U), and Xeomin® (0.06U). The animals were then observed on days 7, 14, 18, 22, and 28 for the development of mechanical allodynia using Von Frey filaments via the "up and down" method, and spontaneous pain behavior was assessed by visual observation of facial rubbing (the act of scratching the face). In mechanical allodynia, on day 22, the Xeomin® brand promoted the greatest improvement, with a 70.3% increase in the withdrawal threshold compared to the CFA group, followed by Botox® (63.8%) and Dysport® (60.1%). Furthermore, all brands significantly reduced facial friction time on day 22. Xeomin® showed a 58.45% reduction in friction compared to the CFA group, while Botox® and Dysport® showed reductions of 52.95% and 48.02%, respectively. Therefore, the three brands of botulinum neurotoxin type A (BNTs-A) evaluated—Botox®, Dysport®, and Xeomin®—demonstrated analgesic potential in the treatment of chronic orofacial pain in a TMD model.