Lidocaine Nerve Block Diminishes the Effects of Therapeutic Electrical Stimulation to Enhance Nerve Regeneration in Rats

Abstract

Background: Although electrical stimulation (ES) can improve nerve regeneration, the impact of nerve block, such as lidocaine (Lido), on the therapeutic benefits of ES remains unclear. We used a rat tibial nerve transection-and-repair model to explore how either preoperative (PreOp) or postoperative (PostOp) nerve block affects ES-related improvement in regeneration. Methods: Lewis rats were used in 1 of 2 studies. The first evaluated the effects of extraneural Lido on both healthy and injured nerves. In the second study, rats were randomized to 5 experimental groups: No ES (negative control), PreOp Lido, ES + PreOp Lido, PostOp + ES, and ES (positive control). All groups underwent tibial nerve transection and repair. In both studies, nerves were harvested for histological analysis of regeneration distal to the injury site. Results: Application of extraneural Lido did not damage healthy or injured nerve based on qualitative histological observations. In the context of nerve transection and repair, the ES group exhibited improved axon regeneration at 21 days measured by the total number of myelinated fibers compared with No ES. Fiber density and percentage of neural tissue in the ES group were greater than those in both No ES and PreOp Lido + ES groups. ES + PostOp Lido was not different from No ES or ES group. Conclusions: Extraneural application of Lido did not damage nerves. Electrical stimulation augmented nerve regeneration, but Lido diminished the ES-related improvement in nerve regeneration. Clinical studies on the effects of ES to nerve regeneration may need to consider nerve block as a variable affecting ES outcome.

Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves

“…Electrical stimulation (ES) of muscles is a standard manipulation by physiotherapists aiming to prevent denervation atrophy and joint fixation [ 16 , 17 ]. In contrast, ES for injured nerves has been a more recent approach to promote muscle and sensory reinnervation [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], and these findings of Brushart and Gordon are largely confirmed by many investigators [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. This review considers (1) how and why functional recovery is poor after peripheral nerve injury, and (2) the efficacy of neurotrophic factors and/or brief low-frequency ES to counteract the negative effects of delayed surgical repair as a prelude to advocate ES to promote nerve regeneration and functional recovery after human nerve injuries.…”

“…The efficacy of ES in promoting nerve regeneration [ 20 , 21 , 22 , 23 , 24 ] has been confirmed [ 18 , 19 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and reviewed [ 53 , 56 , 57 , 58 , 59 , 60 , 61 ]. There are additional studies demonstrating that ES (1) accelerates nerve regeneration through a nerve isograft of 10 mm in Lewis rats [ 46 ] and through 10 and 20 mm nerve autografts in Sprague-Dawley rats [ 47 ], (2) increases the number of macrophages and neutrophils in the denervated distal nerve stumps as well as the number of M2 macrophages within autografts [ 46 , 50 ], (3) shifts the macrophage phenotype in a locally demyelinated peripheral nerve from the proinflammatory M1 toward the predominantly pro-repair M2 type [ 338 ], (4) accelerates Wallerian degeneration and upregulates BDNF and NGF in denervated SCs [ 339 ], and (5) together with testosterone administration promotes facial nerve regeneration and functional recovery of whisking and blink reflexes after crush injury in castrated male rats [ 33 , 36 ] in association with a more rapid and sustained upregulation of BDNF than either alone [ 36 ].…”

“…(2) increases the number of macrophages and neutrophils in the denervated distal nerve stumps as well as the number of M2 macrophages within autografts [46,50], (3) shifts the macrophage phenotype in a locally demyelinated peripheral nerve from the proinflammatory M1 toward the predominantly pro-repair M2 type [338], (4) accelerates Wallerian degeneration and upregulates BDNF and NGF in denervated SCs [339], and (5) together with testosterone administration promotes facial nerve regeneration and functional recovery of whisking and blink reflexes after crush injury in castrated male rats [33,36] in association with a more rapid and sustained upregulation of BDNF than either alone [36]. The infusion of the BDNF antibody, α-BDNF, into the intrathecal space of a rat lumbar spinal cord 3 days prior to (B).…”

The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury

“…In 2000, Al-Majed et al demonstrated that the application of tetrodotoxin, a voltage-gated sodium channel blocker, to a repaired nerve, eliminated the pro-regenerative effects of ES by blocking retrograde action potential propagation [ 17 ]. A recent study by Keane et al found that the administration of perioperative lidocaine significantly diminished the ES-related improvement in nerve regeneration ( Figure 3 ) [ 105 ]. The interaction between ES and peripheral nerve blocks is critical to recognize when designing clinical trials [ 105 ].…”

“…A recent study by Keane et al found that the administration of perioperative lidocaine significantly diminished the ES-related improvement in nerve regeneration ( Figure 3 ) [ 105 ]. The interaction between ES and peripheral nerve blocks is critical to recognize when designing clinical trials [ 105 ]. These results suggest that general anesthesia must be used when using ES during peripheral nerve repair.…”