Electrical Stimulation of Denervated Muscle: A Narrative Review

Chu, L ORCID: 0000-0001-7626-9610, Jarvis, JC ORCID: 0000-0001-8982-6279, Andrews, BJ and FitzGerald, JJ (2025) Electrical Stimulation of Denervated Muscle: A Narrative Review. Artificial Organs. ISSN 0160-564X

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Abstract

Background: Electrical stimulation is commonly employed for activation of paralyzed muscles in patients with neurological diseases and injuries. However, there are differences in the treatment approaches that are possible for upper motor neuron and lower motor neuron injuries.

Methods: This narrative review synthesizes findings from preclinical studies and clinical reports published over the past decades. Key topics include stimulation parameters, muscle physiology under denervation, and outcomes of invasive and noninvasive interventions. The selection of sources was based on their relevance to denervated muscle stimulation in both experimental and therapeutic contexts.

Results: This review critically examined the physiological and therapeutic differences between indirect and direct stimulation of muscles in upper motor neuron and lower motor neuron injury situations. It then focused on the much less well-established field of stimulation of denervated muscle, where there remains a pressing need for new clinical approaches. We explained the rationale for stimulating denervated muscles and the practical difficulties encountered in doing so, describing the use of both invasive and noninvasive devices in animal experiments and clinical trials. We then discussed related research using artificial reinnervation for denervated muscle stimulation and suggested directions for future exploration in this dynamic field.

Conclusion: Stimulation of denervated muscle remains a promising but underdeveloped area. Electrical stimulation of denervated muscle can preserve muscle mass and potentially restore function. However, its clinical adoption has been limited by the exceptionally high stimulation thresholds required, which are approximately one thousand times higher than those for indirect muscle stimulation via intact lower motor neurons. These demands lead to significant challenges including discomfort, limited specificity due to the need for large electrodes, and the risk of tissue damage. Artificial reinnervation may offer a promising solution by enabling the use of conventional low-energy stimulation techniques. Additionally, the application of stimulation in free muscle transfers may further expand therapeutic options in this area.

Item Type:	Article
Uncontrolled Keywords:	artificial reinnervation; denervated muscle stimulation; direct muscle stimulation; electrical stimulation; foot drop; functional electrical stimulation; indirect muscle stimulation; muscle transfer; neuronal grafts; 40 Engineering; 4003 Biomedical Engineering; Rehabilitation; Neurosciences; Musculoskeletal; Neurological; 0903 Biomedical Engineering; 1103 Clinical Sciences; Biomedical Engineering; 4003 Biomedical engineering
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Wiley
Date of acceptance:	8 December 2025
Date of first compliant Open Access:	15 January 2026
Date Deposited:	15 Jan 2026 15:07
Last Modified:	15 Jan 2026 15:07
DOI or ID number:	10.1111/aor.70076
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27915

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