Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial.

Introduction

The human hand is a rich sensory and motor multifunctional tool with dexterous control to perform essential manipulation tasks.¹ Peripheral nerve injuries, especially of the upper limb, can result in severe disability and reduced quality of life.^2–4 Several strategies^5–8 including the use of neurotrophic factors, stem cell therapy,^9,10 and electrical stimulation,¹¹ have been investigated to promote peripheral nerve regeneration as well as functional recovery after these traumas.¹² Electrical stimulation has also been considered as an ancillary to surgical repair, and its effects on nerve recovery has been the focus of several studies.^13–25

It is to be noted that the characteristics and regenerative potential of peripheral nerves differ markedly depending on the location and type of lesion.²⁶ Differences in digital nerve lesions compared with more proximal and mixed lesions are described.^26,27 Digital nerves are almost exclusively sensory, and injuries to these nerves, properly repaired, generally have shorter regeneration distances and can serve as a model for evaluating the effects of transcutaneous electrical nerve stimulation (TENS).²⁷ By contrast, proximal nerve injuries, or nerve injuries with larger gaps to overcome, may be more difficult to completely regenerate, given the increased length for axonal growth and the complexity of motor and sensory functional recovery.²⁸

There are different ways to deliver the PES such as implanted electrodes,^15,16 percutaneous electrostimulation^17,18 (acupuncture needles inserted into the skin and connected to an electric current generator), intraoperative electrostimulation,^19–23 thin-film wireless implantable nerve stimulators,²⁴ and surface electrodes.²⁵ The use of transcutaneous surface electrodes is a non-invasive, practical, and simple option, avoiding the reactions provoked by implant surgery or percutaneous stimulation.²⁹

Based on these features, we hypothesized that PES may influence digital nerve regeneration in humans. We conducted a randomized clinical trial to study the influence of surface PES on the recovery of sensory function, cold sensitivity, and pain disability on the social participation of patients undergoing neurorrhaphy of digital nerves of the hand.

Methods

This double-blind, randomized, controlled clinical trial was conducted at a general hospital in Bahia, Brazil, from December 19, 2020, to June 10, 2022. The study was prospectively registered in the Brazilian Clinical Trials Registry (ReBEC) on December 18, 2020 (registration number: U1111-1259-1998; available at: https://ensaiosclinicos.gov.br/rg/RBR-8xn3qq5). Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine of Bahia, and the study protocol was published³⁰ in advance to ensure methodological transparency and compliance with the Declaration of Helsinki.³¹

Interventions

All patients underwent standardized microsurgical neurorrhaphy under ultrasound-guided axillary block, with epineural approximation using 2 to 4 nylon 8-0 sutures to align nerve fascicles and minimize trauma. Within 24 hours after surgery, participants were randomly allocated to one of two groups.

The stimulation parameters were chosen based on previous studies related to nerve regeneration and patient safety.^11,14,15,19 Group A (Surgery + PES) received one hour of transcutaneous electrical stimulation using the Neurodyn II device (Ibramed, Brazil), delivering a square-pulsed, biphasic, symmetrical current at 20 Hz with a 0.4 ms pulse width, at the motor threshold of the median nerve. Group B (Surgery + sham PES) underwent an identical setup with the same device and electrode positioning, but after an initial perceptible activation, the device output was reduced to zero for the remainder of the session. In both groups, two 1 x1 cm silicone-carbon gel electrodes were positioned proximally and distally to the surgical site ensuring identical placement to maintain blinding of both participants and the administering physiotherapist ( Figure 2). A certified physiotherapist, blinded to the group allocation, supervised the rehabilitation protocol. Sessions were remotely monitored via electronic platforms such as WhatsApp or Skype. Patients underwent a hand sensory re-education program based on the approach proposed by Dellon & Jabaley (1982),³² focused on hand sensory re-education over 3-month period. Participants were also encouraged to perform complementary exercises in a home-based program.

Figure 1. CONSORT 2010 flowchart diagram of patient screening, intervention, and follow-up.

*Intention-to-treat (ITT) analysis.

Figure 2. Model of a repaired digital nerve injury of the index finger and the electrodes placement.

Results

Eligibility was evaluated in a total of 54 patients. Of these, 21 did not meet the inclusion criteria, and one declined to participate. Thus, 32 patients were randomized, with 16 allocated to the PES group and 16 to the sham group ( Figure 1). Baseline characteristics were comparable between groups, and all participants presented with severe sensory impairment on preoperative evaluation, assessed by MSW and s2PD tests ( Table 1). No significant differences between groups were observed during the immediate postoperative period (up to one week; p > 0.05), so subsequent statistical analyses focused on the 1- and 3-month follow-up data.

Sensory outcomes improved over time in both groups, with significant changes observed between 1 and 3 months postoperatively. For SWM values, there was a significant effect of time (p = 0.012), indicating overall sensory recovery. Age showed a marginal influence on SWM outcomes (p = 0.082), becoming significant when scores were converted to needle size (p = 0.014) ( Figure 3). However, no significant differences were found between the PES and sham groups at any time point (p > 0.05). Simillarly, s2PD values demonstrated significant improvement over time (p = 0.002), with age showing a trend toward significance (p = 0.083), but again without significant differences between groups.

Figure 3. Top panels: Average MSW (g, left panel) and s2PD (mm, right panel) of Group A (PES, green line) and B (sham, orange line) 1 and 3 months postoperative.

Bottom-panels: Boxplot of CSS (left panel) and PDI (right panel) for Groups A and B. Error bars represent standard error of the mean.

For secondary outcomes, CSS and PDI scores at the 3-month follow-up were compared between groups using an independent samples t-test. No statistically significant differences were found. However, the two scales were highly correlated (r = 0.819, p < 0.001), suggesting consistent subjective perception of disability and cold sensitivity among patients. To assess the robustness of the results, the analyses were repeated under two conditions: (1) excluding age as a covariate, and (2) removing an outlier – a 57-year-old participant from the PES group with discrepant SWM values (z-score ≈ 5). Exclusion of age as a covariate did not affect the main findings. However, removal of the outlier nullified the previously observed significance of age, indicating sensitivity of the result to the outlier.

In summary, the results show that patients from both groups recovered gradually their sensitivity as measured by MSW and s2PD tests, reaching a satisfactory level at the last measurement. However, no significant effect was found for the treatment at the end of the three measurement moments after the operation.

Discussion

This randomized controlled trial investigated the effectiveness of surface PES in promoting sensory recovery following digital nerve neurorrhaphy. Both groups exhibited a gradual recovery of sensory function over the 3-month follow-up, as measured by SWM and s2PD tests. However, no statistically significant effect of PES was observed at either follow-up time point. It is unlikely that the hypothesized treatment effect was masked by the good recovery of the patients, as after 1 month, sensitivity was still highly affected. Although age showed a near-significant effect in some models, its overall influence appears limited. Cold sensitivity and pain-related disability were assessed only at the final follow-up and showed high inter-individual variability, limiting the ability to draw definitive conclusions regarding these secondary outcomes. Transcutaneous electrical stimulation holds promise in nerve regeneration, offering a non-invasive approach with potential practical benefits.⁴⁰ It can be utilized to circumvent the complications of surgical implantation or percutaneous stimulation.^41,42 Some research indicates that it may take up to 8 weeks for the regenerating axons to cover a distance of 25mm, and the use of PES may reduce this period.^20,26 Previous results demonstrated that subjects who received stimulation exhibited earlier and better outcomes around 3 months post-surgery.²⁶ Gordon at al. (2010)²³ conducted an innovative randomized controlled trial (RCT) of 21 patients undergoing carpal tunnel decompression surgery. Postoperative direct nerve stimulation using implanted wires (20 Hz, 4-6 volts 0.1-0.8 ms) for one hour led to earlier improvements in electrophysiological parameters when compared to controls. Simillarly, Wong et al. (2015)²⁶ conducted a double-blind RCT involving 31 patients with transected digital nerves and observed significantly improved sensory outcomes with PES (20 Hz, <30 V, 0.1–0.4 ms), although no differences in overall functional recovery were found. In another trial, Power et al. (2020)⁴³ evaluated PES following cubital tunnel decompression in 31 patients. The intervention group received a single 1-hour session of PES (20 Hz, <30 V, 0.1 ms) and demonstrated greater improvements in Motor Unit Number Estimation (MUNE) over time compared to the control group.

Some studies reported adverse findings that contradict prior research that has highlighted the advantageous impact of direct current electric fields on the regeneration of peripheral nerves.^44,45 In the present trial, neither the s2PD nor the SWM tests demonstrated a significant enhancement in tactile receptor reinnervation in the digital pulp among patients who received PES. Given these results, the effectiveness of transcutaneous applied electrical fields in promoting in vivo peripheral nerve regeneration remains uncertain.

Cold intolerance⁴⁶ and pain⁴⁷ are commonly reported sources of substantial morbidity following nerve injuries in the hand. Previous studies have associated the severity of these symptoms with the degree of sensory recovery, with poorer reinnervation correlating with more pronounced functional impairment and discomfort.^47,48 In the present sample, isolated digital nerve injuries were not associated with worse outcomes in terms of pain or cold intolerance, as measured by the CSS and PDI. These symptoms appear to be more commonly linked to complex cases involving finger replantation, severe vascular compromise, or proximal nerve injuries of the median or ulnar nerves.

Postoperative rehabilitation following hand neurorrhaphy is considered standard of care⁴⁹ and was prescribed for all participants in this study. Withholding rehabilitation would be ethically inappropriate, as hand therapy is routinely recommended after surgery in real-world clinical settings. Omission of such care could also compromise the study’s external validity. Nevertheless, it is important to acknowledge the potential for interaction effects between the rehabilitation protocol and the electrical stimulation intervention,⁵⁰ which may have limited the ability to isolate the specific contribution of PES to sensory recovery.

The use of a digital nerve injury model in this study presents inherent limitations regarding the generalizability of the findings. Digital nerve injuries differ substantially from proximal or mixed nerve lesions, particularly due to the shorter axonal regeneration distances and the absence of motor components. These factors may have contributed to a ceiling effect, whereby the sensitivity of the outcome measures is insufficient to detect additional improvements potentially attributable to PES.^51–53 Consequently, although our findings provide insight into the effects of PES on sensory nerve regeneration in the hand, they may not be directly applicable to more severe or complex nerve injuries requiring longer regenerative distances. Future studies should consider the use of more complex clinical models, such as proximal or mixed nerve injuries, to better assess the potential of electrical stimulation in promoting meaningful functional recovery.

Conclusion

In this study, the use of surface electrical stimulation following neurorrhaphy in the hand did not result in improved postoperative sensory recovery, as assessed by the SWM and s2PD tests. No significant differences were observed in cold sensitivity or pain-related disability outcomes between the intervention and control groups. These findings suggest that, within the context of isolated digital nerve injuries, surface PES may not confer additional clinical benefit beyond standard surgical repair and rehabilitation. Further research is warranted to explore the efficacy and safety of electrical stimulation protocols in more complex nerve injury models and under varying clinical conditions.

Ethical considerations

This study was approved by the Research Ethics Committee of the Faculty of Medicine of Bahia (Federal University of Bahia), under protocol number 4.430.230. All procedures were conducted in accordance with the Declaration of Helsinki. The study was prospectively registered in the Brazilian Clinical Trials Registry (ReBEC) under registration number U1111-1259-1998.

Consent to participate

All participants provided written informed consent prior to enrollment in the study, including consent for surgical intervention, application of surface electrical stimulation, and participation in follow-up assessments.