Photobiomodulation for Median Nerve Neuroplasticity in Carpal Tunnel Syndrome: A Randomized Controlled Trial

Carpal Tunnel Syndrome (CTS) is the most common peripheral entrapment neuropathy, causing pain, paresthesia, and hand dysfunction due to median nerve compression at the wrist. While physiotherapy provides symptom relief, it does not effectively address the underlying neuroplastic deficits of the median nerve. Photobiomodulation (PBM), delivered at 830 nm near-infrared wavelength, has shown potential to enhance peripheral nerve regeneration via cytochrome c oxidase activation, ATP synthesis, and upregulation of neurotrophic factors including brain-derived neurotrophic factor (BDNF). This randomized controlled trial will evaluate whether 830 nm PBM (200 mW, 4 J/cm², 12 sessions over 4 weeks) combined with routine physiotherapy produces significantly greater neuroplastic recovery of the median nerve - assessed by high-resolution ultrasound (HRUS) measurement of median nerve cross-sectional area (CSA), nerve conduction study parameters and serum BDNF - compared to sham PBM combined with identical physiotherapy in adults with mild-to-moderate CTS. Neuroplasticity was operationalised as a multimodal construct comprising: (1) functional recovery, indexed by nerve conduction study parameters; (2) structural remodelling, indexed by median nerve cross-sectional area on high-resolution ultrasound; and (3) molecular neuroplastic signalling, indexed by serum BDNF. This multimodal approach was adopted because no single measure captures the full construct of peripheral nerve neuroplasticity (Padua et al., 2020).

Inclusion criteria * Age 18-60 years * Clinical diagnosis of unilateral mild-to-moderate carpal tunnel syndrome based on positive Phalen test and/or Tinel sign * Electrophysiological confirmation of CTS via nerve conduction study (NCS) meeting AANEM 2012 diagnostic criteria for mild-to-moderate CTS * No prior photobiomodulation or laser therapy to the affected wrist within the preceding 3 months * Ability to attend 3 treatment sessions per week for 4 consecutive weeks * Able and willing to provide written informed consent (in Urdu or English) Exclusion Criteria * Bilateral carpal tunnel syndrome * Previous surgical release of the carpal tunnel on the affected side * Systemic peripheral neuropathy (e.g., diabetes mellitus, hypothyroidism, Charcot-Marie-Tooth disease) * Pregnancy or breastfeeding * Implanted cardiac pacemaker, defibrillator, or other active electronic implant * Active malignancy at or near the treatment site * Current use of photosensitising medications (e.g., tetracyclines, amiodarone, psoralens) * Corticosteroid injection into the carpal tunnel within the preceding 3 months * Rheumatoid arthritis or other inflammatory joint disease affecting the wrist * Open wounds, acute skin infection, or tattooed skin at the treatment site * Inability to attend 3 sessions per week for 4 weeks * Severe CTS confirmed by NCS (complete sensory or motor axon loss)