Intrathecal administration of botulinum toxin type a antagonizes neuropathic pain by countering increased vesicular nucleotide transporter expression in the spinal cord of chronic constriction injury of the sciatic nerve rats

• Published in: Neuropeptides (Edinburgh) 2023-08, Vol.100, p.102346-102346, Article 102346
• Main Authors: Shi, Yongqiang, Gong, Chaoyang, Nan, Wei, Zhou, Wenming, Lei, Zeyuan, Zhou, Kaisheng, Wang, Linna, Zhao, Guanghai, Zhang, Haihong
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Botulinum toxin type a; Botulinum Toxins, Type A - metabolism; Botulinum Toxins, Type A - pharmacology; Botulinum Toxins, Type A - therapeutic use; Constriction; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Neuralgia - drug therapy; Neuralgia - metabolism; Neuropathic pain; Nucleotides - metabolism; Nucleotides - pharmacology; Rats; Sciatic Nerve; SNAP-25; Spinal Cord - metabolism; VNUT
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2023.102346

Botulinum toxin type A (BoNT/A) induces direct analgesic effects in neuropathic pain by inhibiting the release of substance P, calcitonin gene-related peptide (CGRP) and glutamate. Vesicular nucleotide transporter (VNUT) was responsible for the storage and release of ATP in vivo, and one of the mechanisms underlying neuropathic pain is VNUT-dependent release of extracellular ATP from dorsal horn neurons. However, the analgesic effect of BoNT/A by affecting the expression of VNUT remained largely unknown. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of BoNT/A in chronic constriction injury of the sciatic nerve (CCI) induced neuropathic pain. Our results showed that a single intrathecal injection of 0.1 U BoNT/A seven days after CCI surgery produced significant analgesic activity and decreased the expression of VNUT in the spinal cord of CCI rats. Similarly, BoNT/A inhibited the CCI-induced increase in ATP content in the rat spinal cord. Overexpression of VNUT in the spinal cord of CCI-induced rats markedly reversed the antinociceptive effect of BoNT/A. Furthermore, 33 U/mL BoNT/A dramatically reduced the expression of VNUT in pheochromocytoma (PC12) cells but overexpressing SNAP-25 increased VNUT expression in PC12 cells. Our current study is the first to demonstrate that BoNT/A is involved in neuropathic pain by regulating the expression of VNUT in the spinal cord in rats.