The analgesic effect of very low-dose naltrexone (VLDN) was not enhanced by repetitive transcranial magnetic stimulation (rTMS) in rats with temporomandibular joint arthritis.

Abstract

Temporomandibular disorders (TMD) are the most common cause of non-odontogenic orofacial pain (OFP) and involve a wide variety of signs and symptoms, with the potential to impair quality of life and functionality of patients. In this context, it is imperative to investigate new approaches to treat this condition. Thus, the aim of this study was to assess whether the combination of repetitive transcranial magnetic stimulation (rTMS) and very low-dosage naltrexone (VLDN) enhances the effects on the nociceptive response and biomarkers in rats with temporomandibular joint arthritis (TMJA). Forty adult male Wistar rats were used. The TMJA model was established by injecting 50 µL of CFA into the right temporomandibular joint (TMJ). Rats were divided into five groups: sham-CFA (Sh-CFA), TMJA model (CFA), TMJA model plus VLDN (CFA-VLDN), TMJA model plus rTMS (CFA-TMS), and TMJA model plus VLDN plus rTMS (CFA-VLDN-TMS). The nociceptive response was evaluated by facial von Frey and hot-plate tests; behavioral parameters were assessed by the open-field and splash tests. Following the TMJA model establishment, treatment started and consisted of daily sessions of rTMS (5') and/or oral gavage of VLDN (0.5 mg/kg) from the 11th to the 20th day. Rats were euthanized on day 21 to collect prefrontal cortex, serum, and right and left trigeminal ganglion. Biomarkers analyzed were BDNF, TNF-α and IL-4. Ten days after the intra-TMJ injections, rats receiving CFA presented facial mechanical allodynia, but not paw thermal hyperalgesia. Treatment with VLDN reversed it partially, with no effects from rTMS. None of the central and peripheral biomarkers analyzed (BDNF, TNF-α, and IL-4) were linked to the TMJA model, nor to the treatments (VLDN or rTMS). Increased grooming behavior was observed as a result of rTMS. VLDN might be useful as an adjunctive pharmacological therapy for relieving hypernociception resulting from inflammatory facial pain. Further investigations may contribute to the understanding of the action mechanisms of naltrexone.