Neuromodulation for pain and fatigue in hereditary and acquired neuromuscular conditions: a narrative review

Abstract

Introduction Pain and fatigue are highly prevalent in neuromuscular (NM) diseases, including motor neuron, peripheral nerve, junctional, and myopathic pathologies. Their multifactorial pain mechanisms as neuropathic, nociceptive, and mixed often remain resistant to conventional pharmacologic and rehabilitative strategies. The long-term use of opioids carries significant adverse effects. Given these limitations, neuromodulation offers a non-pharmacologic approach to address pain and functional impairment in neuromuscular diseases. Objective This narrative review synthesizes existing evidence and biological rationale for neuromodulation in NM disorders, summarizing prior and ongoing research and outlining future directions for clinical applications. Methods A targeted literature search was performed across PubMed, and ClinicalTrials.gov through October 2025 for human studies using invasive or non-invasive neuromodulation. transcranial direct-current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, peripheral nerve stimulation (PNS), vagus nerve stimulation (VNS), and trigeminal nerve stimulation (TNS) are searched for NM diseases. Eligible studies involved patients with NM diseases reporting pain, fatigue, or functional outcomes. Data were qualitatively synthesized by disease category and stimulation modality, and ongoing clinical trials were summarized. Results The available literature supports a biologically plausible and clinically promising role for neuromodulation in selected neuromuscular pain phenotypes, particularly where neuropathic mechanisms predominate. However, the evidence base remains fragmented, with limited disease specific trials and substantial heterogeneity in patient populations, stimulation parameters, and reported endpoints. These limitations currently prevent definitive conclusions about efficacy or routine clinical applicability. Conclusions Neuromodulation offers an alternative, non-drug option to help relieve pain and fatigue in people with neuromuscular disorders. By targeting maladaptive excitability, central sensitization, and neuro-immune pathways, it holds potential to complement disease-modifying and rehabilitative strategies. However, evidence remains preliminary; standardized multicenter trials, biomarker-guided stratification, and integrative approaches are needed to define efficacy and optimize clinical translation.