Abstract
BackgroundBoNT-A is often used in the clinical treatment for movement disorders. In recent years, various clinical studies suggest that BoNT-A can effectively alleviate pain caused by trigeminal neuralgia (TN); however, its mechanism remains unclear.MethodsIn this study, we used a lab rat model for TN produced by chronic constriction injury of the infraorbital nerve (ION-CCI). Restrained rats were injected subcutaneously with BoNT-A into the whisker pad tissue (ipsilaterally to the nerve injury) 14 days after the ION-CCI. Allodynia was tested by Von Frey filaments and TRPs and cSNAP-25 were tested by western blot.ResultsPeripheral application of BoNT-A (3, 10 U/kg) significantly increased the pain threshold of ION-CCI rats. Rota-rod test showed that BoNT-A administration at doses tested did not significantly affect rat motor coordination. By probing for a specific marker for BoNT-A, cleaved synaptosomal-associated protein 25 (cSNAP-25), we found that peripheral application of BoNT-A (10 U/kg) affected brainstem Vc, which could be blocked by the axonal transport blocker colchicine. In addition, western blot analysis showed that in the Vc region of ION-CCI rats, the expression levels of TRPA1, TRPV1, TRPV2 and TRPM8 increased, whereas peripheral application of BoNT-A significantly lowered the high expression of TRPA1, TRPV1 and TRPV2, but not TRPM8 at 7 days after BoNT-A injection.ConclusionsThe finding of this study suggest that peripherally applied BoNT-A can produce antinociceptive effects in ION-CCI model. The underlying mechanisms may be BoNT-A acts on the Vc via axonal transport, inhibits the high expression of TRPA1, TRPV1 and TRPV2, and reduces central sensitization.
Highlights
Botulinum toxin type A (BoNT-A) is often used in the clinical treatment for movement disorders
Most studies on the mechanism of the antinociceptive effects of botulinum toxin focus on the formalin-induced pain model, as well as pre-application of BoNT-A to explore its role in pain prevention (Cui et al 2004)
Our results showed that 14 days after ION-CCI, the ipsilateral pain threshold of the IONCCI group was significantly reduced compared to the sham-operated group (P < 0.05)
Summary
BoNT-A is often used in the clinical treatment for movement disorders. Various clinical studies suggest that BoNT-A can effectively alleviate pain caused by trigeminal neuralgia (TN); its mechanism remains unclear. Trigeminal neuralgia (TN) is episodic facial pain that is usually described to feel like a unilateral electric shock. This neuropathic disorder has been shown to be profoundly distressing and to negatively impact the patient’s well-being (Hall et al 2006). Most studies on the mechanism of the antinociceptive effects of botulinum toxin focus on the formalin-induced pain model, as well as pre-application of BoNT-A to explore its role in pain prevention (Cui et al 2004)
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