, 2010) needs to be explained. In the end, these are some of the issues that need to be urgently resolved. BoNTs are a group of homologous di-chain proteins (serotypes A-G) with distinct characteristics (Fig. 1). It originates from Clostridium botulinum whose active form consists of a Zn2+-dependent proteolytic light chain (LC, 50 kDa) linked to a heavy chain (HC, 100 kDa) via a disulphide and non-covalent bonds (Dolly and Talazoparib O’Connell, 2012). When BoNTs are injected into a target tissue, its heavy chain binds to glycoprotein structures

specifically found on cholinergic nerve terminals; which can explain its high selectivity for cholinergic synapses. After internalization, the light chain binds to the SNARE protein complex with a high specificity. The target proteins vary amongst the BoNT serotypes (Dressler et al., 2005). What we have focused on in this study is the BoNT/A that cleaves the synaptosomal-associated proteins of 25 kDa (SNAP-25). In 2010, Montal M provided selleck compound an outline of BoNT protein design and function. The HC, HN and LC regions are responsible for binding, translocation and protease activity; respectively (Montal, 2010). In this study, we have tried to combine the information provided to us through literature with the evidence we have found in the animal

models in order to reasonably explain the molecular mechanism of BoNT action. Never the less, further details need to be gathered by more extensive studies. The formalin

model is a preclinical model used to investigate the analgesic effect of some drugs. It always ROS1 elicits pain-related behavior, such as licking, biting and shaking. Injection of formalin into the plantar surface of the hind paw produced a biphasic response of neuronal excitation (Lee et al., 2011). Cui et al. (Aoki, 2005) showed that subcutaneous injection of BoNT/A into the rat paw significantly reduced formalin pain during phase two, inhibited the glutamate release in the hind paw, reduced the number of formalin-induced Fos-like immunoreactive cells in the dorsal horn of the spinal cord and significantly inhibited the excitation of wide dynamic range neurons of the dorsal horn in phase two. All of these findings demonstrated that the BoNT/A does not exert a local analgesic effect but reduces central sensitization (Aoki and Francis, 2011). The capsaicin model of inflammatory pain is to excite the sensory neurons with capsaicin; which is an irritant derivative from chilli peppers. It binds to the cation channel of the transient receptor potential vanilloid type 1 (TRPV1); which is located on C-fibers (Lomas et al., 2008). This model can cause intense pain due to the release of neuropeptides such as substance P and CGRP (Bach-Rojecky and Lackovic, 2005). Bach-Rojecky et al.