| [Background and aims] Botulinum toxin type A (BTX-A) is a potent inhibitor of acetylcholine release in the neuromuscular junction and has been used to treat many disorders related to excessive muscle contraction. However, BTX-A has recently been used in pain therapy to treat not only neuromuscular disorders but also various types of headaches, myofascial pain syndrome, chronic low back pain, plantar fasciitis, chronic prostatic pain and, interstitial cystitis. BTX-A was initially thought to provide pain relief by reducing muscular activity. But many researches suggest that BTX-A may have a more complex mechanism of action on the pain system. BTX-A-mediated antinociceptive effects have been investigated using animal models such as visceral pain and somatic pain. In these studies BTX-A have been shown to reduce peripheral sensitization by inhibiting the release of several neuromodulators including glutamate, substance P and calcitonin gene-related peptide, and reducing c-fos gene expression. The purpose of this study is to investigate the antinociceptive effect of BTX-A and its underlying mechanism in an acetic acid-induced visceral pain model in rats. [Methods] Male Wistar rats of postnatal eight weeks were divided into four groups: BTX-A (2U, 4U, and 6U ) or vehicle (2ml) was injected intraperitoneally of B,C,D and A group rats. Four weeks later, 6 rats of every group were performed with colorectal balloon distention to evaluate colorectal pain threshold . Rats were challenged with acetic acid (2% , 3 ml/ kg) intraperitoneal injection 1 week, 4 weeks and 8 weeks post-BTX-A injection. Abdominal writhing behaviors were monitored in 45 minutes as indicators of pain. The serumal TNF and IL-6 were tested by radioimmunology. The samples of small and large intestine were stained by Haematoxylin-eosin for the routine pathologic examination, and immunohistochemistry for AChE, SP, CGRP. The expression of AChE, SP andCGRP were analyzed by computing image analysis system of image-pro plus 5.0 semi-qualitively. Data were packed up by SPSS 11.5 statistical software with p <0.05 considered significant.[Results] The colorectal pain thresholds in BTX-A pretreated groups were not different significantly from those in the saline group at week 4. At the end of one week, total writhing test scores in 45 minutes of group C and group D were decreased significantly compared with group A (P<0.05); Only the serumal TNF levels of group D were lower than group A; The expression of AChE, SP, CGRP in intestinal walls of BTX-A pretreated groups showed a significant decrease except the positive area of SP in intestinal muscular layer and CGRP in intestinal wall in group B. At week 4,the writhing sores, serumal TNF levels and the expression of AChE, SP, CGRP in BTX-A pretreated groups all showed significant difference compared with those of group A (P<0.05) ,except the levels of serumal TNF in group B and IL-6 in group B and C. After 8 weeks injection, all the effects were not detected in BTX-A treated groups except that the expression of AChE in intestinal wall was still lower than that of group A(P<0.05) .[Conclusions] Injection of BTX-A intraperitoneally significantly reduces acetic acid-induced nociceptive behaviors after 1 week and 4weeks, decreases the level of serumal TNF and IL-6 and inhibits the expression of AchE, SP and CGRP in intestinal wall. All these results were not observed at the end of 8 weeks except reducing AChE expression. Such an antinociceptive effect of BTX-A is postulated with the inhibition of acid-induced release of SP (and/or neuropeptides) from primary afferent terminals and inflammatory factors in serum. However, the effect of BTX-A in other different visceral pain models and the mechanisms still need to be further investigated. These results may support new clinical application of BTX-A for the treatment of visceral pain.
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