Botulinum toxin injection can reduce arthritis pain by inhibiting the expression of calcitonin gene-related peptide in the dorsal root ganglia
10.3760/cma.j.issn.0254-1424.2016.09.003
- VernacularTitle:A型肉毒毒素关节腔注射对佐剂性关节炎疼痛大鼠背根神经节中降钙素基因相关肽表达的影响
- Author:
Chenglei FAN
;
Xiao CHU
;
Kaile WANG
;
Lin WANG
;
Zhenyuan NIU
;
Tieshan LI
- Publication Type:Journal Article
- Keywords:
Botulinum toxin type A;
Arthritis;
Pain;
Calcitonin gene-related peptide;
Dorsal root ganglia;
Retrograde axonal transport
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2016;38(9):652-658
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the analgesic effect of intra-articular botulinum neurotoxin type A (BoNTA) injection in rats with adjuvant-arthritis pain,to quantify the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) associated with arthritis pain,and to investigate the retrograde axonal transport of BoNT-A into the DRG after peripheral injection.Methods Ninety Sprague-Dawley rats were randomly divided into groups A,B,C,D and E,each of 18.A murine model of adjuvant-arthritis pain was established by injecting 50 μL of complete Freund's adjuvant into the left ankle in all the mice except those in group A.The control group A was treated with intra-articular injection of 50 μL of saline solution.Three weeks later,groups A and B were treated with a 20 μL intra-articular saline injection,while groups C,D and E received an intra-articular injection of BoNT-A at 1 U/20 μL,3 U/20 μL or 10 U/20 μL respectively.Pain threshold and muscle strength were graded before and 1,5,15 and 21 days after the modelling,as well as at 1,3,5 and 14 days after the BoNT-A treatments.Protein expression and the CGRP-positive cell number were observed,as well as any BoNT-A-cleaved synaptosomal-associated 25 kDa protein (cl-SNAP-25) in the DRG using Western blotting and immunofluorescence.Results Compared with group A,there was a significant decrease in the average mechanical withdrawal threshold and muscle strength and a significant increase in the protein expression and the CGRP-positive cell number in the other 4 groups.Compared with group B,the mechanical withdrawal threshold had increased significantly more in groups D and E at 5 days after the BoNT-A injection and in group C at 14 days after the treatment.Compared with group B,the protein expression and the number of CGRP-positive cells were significantly lower in groups D and E at 3 days after the BoNT-A injection.The decrease in group C was significant after 14 days.No significant differences were found between groups D and E in any measurement at any time point.There was no significant difference among groups B,C and D in terms of muscle strength.Five days after the BoNT-A injection,significantly decreased muscle strength was observed in group E.In addition,BoNT-A cleaved-SNAP-25 was detected in the DRG.Conclusion BoNT-A can reduce arthritis pain through inhibiting the expression of CGRP in the DRG.Its analgesic effect has a dose response.A peripheral injection of BoNT-A can arrive at the DRG through retrograde axonal transport.
