Pre-operative conditioning with electrical stimulation (ES) of the injured peripheral nerves demonstrates particular promise. The mechanism of action of conditioning lesions consists of up regulation of regenerative associated genes and the cAMP and JAK/STAT pathways. Data from animal models, examining the effect of pre-operative electrical stimulation of peripheral nerves, demonstrate that this technique promotes peripheral nerve axonal regeneration. Senger et al have demonstrated that electrical stimulation produced axonal regeneration that is equivalent to the traditional pre-conditioning crush lesion. Thus, electrical stimulation has been proven as a viable method of pre-conditioning peripheral nerves, in order to promote upregulate axonal regeneration prior to primary coaptation of the nerve. Senger et al have also investigated the mechanism of action of this improved axonal regeneration in animals pre-conditioned with electrical stimulation and have found upregulation of regenerative associated genes.