| BackgroundThoracic outlet syndrome(TOS)is a group of disorders that occurs when the brachial plexus or subclavian artery and vein in the thoracic outlet(a broad anatomical area from the intervertebral foramen to the inferior border of the pectoralis minor muscle)are compressed,which could cause pain,paresthesia,ischemia and weakness in the hand,arm,and shoulder.TOS is one of the most challenging surgical diseases for the difficulties in diagnosis and the controversies in treatment,as its clinical symptoms are highly similar to those of cervical spondylosis and neuropathy.The incidence of TOS is between 3 to 80 cases per 1000 people.Diagnostic scalene muscle block(DSMB)is a recognized and objective method of diagnosing thoracic outlet syndrome.By injecting drugs into the muscles(e.g.,scalene muscle)that cause neurovascular compression,the symptoms are relieved from the muscle block,resulting in muscle relaxation and even paralysis,which confirms the diagnosis of thoracic outlet syndrome.Besides,a positive response to DSMB has been reported to predict surgical outcomes,such as anterior scalene muscle and first rib resection in thoracic outlet syndrome treatment,which can provide assistance in the surgical decision.DSMB is usually performed with lidocaine,which inhibits action potential conduction by blocking Na~+-voltage-gated channels.However,there are also some reports that the performance of lidocaine in DSMB is not satisfactory.Recently,clinical studies have also reported the use of botulinum toxin A(BTX-A)in the treatment of thoracic outlet syndrome.BTX-A is a neurotoxin of high molecular protein produced by clostridium botulinum,which mainly inhibits the release of acetylcholine from nerve endings and causes a characteristic flaccid paralysis of the muscles.However,the clinical application of BTX-A in SMB is still not common,and no consensus is reached on the dosage.Therefore,it would be important to investigate and compare the efficiency of lidocaine and BTX-A in muscle block.This study will contribute to the choice of the drug when performing DSMB in clinical practice.ObjectiveOur research aims to compare the efficacy of lidocaine and BTX-A in blocking skeletal muscle contraction in rats and provide a better choice for TOS diagnosis.MethodsAn optimal drug for DSMB should substantially inhibit muscle contraction by measuring muscle strength.Due to the difficulty in measuring scalene muscle strength either in patients or rats,this study compared the blocking efficiency of lidocaine and BTX-A in the tibialis anterior(TA)muscles of rats,whose strength could be easily and repeatedly measured through ankle dorsiflexion.1.SD rats(265±17 g)were chosen for experiments.After anesthesia,the left tibialis anterior muscle was stimulated using a sequence of tonic contraction stimuli(1m A,400 ms)at 1-min intervals of 20 Hz,40 Hz,50 Hz,60 Hz,80 Hz,100 Hz,and muscle force and integration were recorded.After 2 min of rest,the muscle was stimulated with 3 tetanic(1 m A,400 ms)of 100 Hz at 1-min intervals,obtaining the mean value of the muscle force.Lidocaine at the concentration of 0.5%,1%and 2%were injected into the middle of the left anterior tibial muscle at the maximum volume or half-maximum volume that muscles could hold,respectively.Saline was used as a control.Measurements were performed at 30 min,1 h,1.5 h,2 h,2.5 h,3 h and 6 h after drug administration,respectively.2.To evaluate the efficacy of synergy for lidocaine in DSMB(e.g.with epinephrine,dexamethasone,multi-point injections),the measurement was performed as described earlier in the following groups:(1)2%lidocaine+epinephrine(1:200,000,5μg/m L);(2)epinephrine(1:200,000,5μg/m L);(3)2%lidocaine+dexamethasone(1.28 mg/m L);(4)dexamethasone(1.28 mg/m L);(5)2%lidocaine,drugs were injected into both the middle point and the location 5 mm away from the middle point on the TA muscle.Additionally,the blood flow was observed with a laser scattering blood flow detector.3.For the blocking efficacy of BTX-A,a similar test was performed in the following groups:(1)3 U/kg BTX-A;(2)6 U/kg BTX-A;(3)12 U/kg BTX-A;(4)2%lidocaine;(5)2%lidocaine+epinephrine(1:200000,5μg/m L).Measurements were performed before and from day 1 to day 7 after the drug injection.4.Gait analysis of rats was conducted and analyzed with the Digi Gait system.To assess the biosafety of BTX-A,immunohistochemistry staining of c-SNAP-25 was carried out on the sections of the tibialis anterior muscle,extensor digitorum longus muscle,common peroneal nerve and lumbosacral spinal cord in the BTX-A treated rats.Results1.The maximum injection volume in the tibialis anterior muscle of rats is 40μL.For lidocaine,the blocking efficiency increases with its concentration,and the strongest potency of muscle block is reached with 2%lidocaine in 40μL,resulting in a 61%±14%decrease in the muscle force.2.Lidocaine in combination with epinephrine could significantly prolong the duration of the block,but not the blocking potency(P=0.504).Lidocaine in combination with dexamethasone or multipoint injection,however,did not affect the blocking potency of lidocaine.3.BTX-A largely blocked the contraction of skeletal muscles.The reduction ratio of maximum force was ranging from 82%to 95.5%after BTX-A administration.The blocking effect lasted till the seventh day when the experiment was terminated.4.In the 12 U/kg BTX-A group,a significant reduction of the contact area between the left hind paw of rats and the ground was observed via gait analysis,so did the delay in heel lifting up.Compared with lidocaine,BTX-A caused a decrease in the wet weight of the injected muscle.Though BTX-A was injected into the tibialis anterior muscle,c-SNAP-25 was observed in extensor digitorum longus muscle in the 6 U/kg and 12 U/kg groups,but negative in the 3U/kg group.c-SNAP-25 also existed in the common peroneal nerve in all BTX-A groups.However,c-SNAP-25 was not detectable in the corresponding spinal cord segmental sections.Conclusions1.Lidocaine partly blocks the contraction of the muscle,and its efficiency correlates with concentration.2.Lidocaine combined with epinephrine prolongs the duration of muscle block.Multiple site injection or in combination with steroid is not able to enhance the blocking effect of lidocaine.3.Low dose of BTX-A(3U/kg)leads to a large extent of muscle block.4.Low dose of BTX-A(3U/kg)does not block the adjacent muscles or affect the central nervous system.5.Low dose of BTX-A(3U/kg)is more suitable for muscle block than lidocaine,making it a potential drug for diagnostic scalene muscle block of thoracic outlet syndrome in clinic. |
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