Study On Spread Of Intramuscular Injection Of Botulinum Toxin Type A

Backgroud:Botulinum neurotoxins have been classified into7serotypes (A-G), according to their immunological characteristics. They Specifically cleave synaptosomal-associated protein of25kDa (SNAP-25), which belongs to SNARE and resides in presynaptic membrane, turn SNAP-25into cleaved SNAP-25(c1.SNAP-25) and mainly exerted as an inhibitor of evoked acetylcholine release from cholinergic nerve endings, and resulting in paralysis. BTX-A is widely used to treat a variety of clinical conditions characterized by muscle hyperactivity, such as dystonia and spasticity. BTX-A is locally applied, with little or absent diffusion, and its paralyzing action remains confined to the nerve muscle junction, close to the injection site. This assumption constituted a "dogma" for many years in the use of these neurotoxins in human therapy. However, more and more recent studies suggest that BTX-A also has central effects and some investigators demonstrated that BTX-A enter central nervous system after local intramuscular administration via retrograde transport, although the evidences were relative insufficient.Objective:In this study, we will investigate the retrograde axonal transport of BTX-A into the central nervous system after peripheral injection, via the detection of cleaved SNAP-25as an assay of BTX-A trafficking, and remote muscle also have been taken into consideration. Then we discuss the possible meachnisms underlie these central effects. In the end, this research will provide essential information for clinical treatment.Methods:1) Unilaterally administrate three different dosage of BTX-A into gastrocnemius, and detect c1.SNAP-25in contralateral muscle after three different time point.2) C1.SNAP-25also been detected in sciatic nerve and spinal cord to confirm that whether BTX-A can spread to central nerve system via retrograde transport or not.Results:1) No matter which dose of BTX-A can cleave the SNAP-25located in contralateral neuromuscular junction.2) C1.SNAP-25can not be detected, even under influence of maximum tolerated safe dose of BTX-A in sciatic nerve or spinal cord.3) The compensation of SNAP-25in neuromuscular junction and sciatic nerve can been detected after injection of three different dosage of BTX-A.Conclusions:1) Even very low dose of BTX-A can also cleave the SNAP-25located in contralateral neuromuscular junction via blood circulation.2) Even maximum tolerated safe dose of BTX-A can not induce retrograde transport to sciatic nerve or spinal cord.3) Central nerve system compensate SNAP-25cleaved by BTX-A.