Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia.
BACKGROUND
BoNT-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.


METHODS
In 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.


RESULTS
Peripheral 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.


CONCLUSIONS
The 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.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Chuanjie
C
Wu
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Nanchang
N
Xie
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Yajun
Y
Lian
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Hongliang
H
Xu
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Chen
C
Chen
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Yake
Y
Zheng
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Yuan
Y
Chen
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Haifeng
H
Zhang
Botulinum toxin type A; Central antinociceptive activity; Rat; Trigeminal neuralgia