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[JK-03] Application of botulinum toxin type A in chronic orofacial pain: Animal researches

Dong Kuk Ahn (Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea)

Keywords:Botulinum toxin type A, anti-nociception, neuropathic pain, trigeminal neuralgia, inflammatory pain

Botulinum toxin (BoNT) is a potent neurotoxin produced by the bacterium Clostridium botulinum, which acts by blocking acetylcholine release at the neuromuscular junction. Recent data support the evidences for use of BoNT-A in treatment of several painful states. In the present study, we investigated the anti-nociceptive effects of BoNT-A in a rat model of inflammatory, neuropathic pain, trigeminal neuralgia in the orofacial area. Experiments were carried out in male Sprague-Dawley rats. We used several chronic pain models in the present study. Orofacial formalin responses and CFA-induced thermal hypersensitivity were observed as an inflammatory pain. We also examined mechanical allodynia in rat models of trigeminal neuropathic pain and trigeminal neuralgia. Subcutaneous injection of BoNT-A produced significant suppression of formalin-induced nociceptive behavior and CFA-induced thermal hyperalgesia. Intracisternal injection of BoNT-A also produced significant antinociceptive effects in same animal models. A single injection of 3 U/kg BoNT-A produced prolonged anti-allodynic effects in a rat with inferior alveolar nerve Injury. Double treatments with 1 U/kg BoNT-A produced prolonged anti-allodynic effects compared with single treatments. Besides, treatment with BoNT-A on postoperative day 7 and 12, when pain had already been established, also produced prolonged anti-allodynic effects. Peripheral administration of BoNT-A produced anti-allodynic effects in a rat model with trigeminal neuralgia. The present also deals with underlying mechanism of antinociceptive effects of BoNT-A in the trigeminal neuropathic pain and trigeminal neuralgia. Subcutaneous injection of BoNT-A produced prolonged anti-nociception in chronic orofacial pain diseases. Therefore, BoNT-A is a potential new therapeutic agent for chronic pain control in the orofacial area.

Acknowledgments:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2017R1A5A2015391 and 2022R1A2C2092262) and by Hugel Inc. (Chuncheon, Republic of Korea). We are grateful to Hugel Inc. for providing Botulax®.