RMD/
Articles/
2601002913
  • Open Access
  • Review

mTOR Signalling in Diabetic Peripheral Neuropathy: Balancing Neuropathic Pain and Schwann Cell-Mediated Repair

  • Ka Huen Cheng 1,2,   
  • John Akrofi Kubi 1,2,*,   
  • Augustine Suurinobah Brah 1,2,   
  • Mireku Yaw Asante 1,2,   
  • Yizhou Zhu 1,2,   
  • Kelvin Wai Kwok Yeung 1,2,*

Received: 07 Dec 2025 | Revised: 19 Jan 2026 | Accepted: 23 Jan 2026 | Published: 02 Feb 2026

Abstract

Diabetic peripheral neuropathy (DPN) is a prevalent secondary complication of diabetes mellitus, characterised by nerve fibre degeneration, neurosensory deficits, and chronic neuropathic pain, all of which have significant clinical impact by increasing disability, reducing quality of life, and complicating diabetes management. While oxidative stress and neuroinflammation are established contributors to DPN pathogenesis, the specific involvement of the mammalian target of rapamycin (mTOR) signalling pathway in DPN remains incompletely defined. Recent findings indicate cell-type-specific dysregulation of mTOR signalling in diabetic peripheral nerves, with direct implications for targeted clinical interventions. This review outlines the pathophysiology, clinical manifestations, and therapeutic approaches for DPN, with a particular emphasis on the differential regulation of mTOR signalling in sensory neurons and Schwann cells. A greater understanding of these molecular mechanisms could improve diagnosis and refine treatment plans for DPN patients in clinical settings. Literature published from 1990 to 2025 was systematically reviewed to enhance understanding of the mTOR pathway’s contributions to DPN pathogenesis. This review clarifies that mTOR operates differently in sensory neurons and Schwann cells during persistent hyperglycaemia in DPN. Overactive mTOR in sensory neurons increases neuropathic pain by enhancing neuron excitability, altering ion channels, and disrupting synapses. In vitro studies indicate reduced mTOR activity in Schwann cells, likely impairing repair processes such as dedifferentiation, survival, myelin production, and nerve support. Human tissue studies yield mixed results, leaving the consistency of these changes across patients unresolved. Consequently, further research is essential to clarify the precise and consistent impact of mTOR alterations in specific cell types.

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10.53941/rmd.2026.100002
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Volume 3, Issue 1
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Cheng, K. H.; Kubi, J. A.; Brah, A. S.; Asante, M. Y.; Zhu, Y.; Yeung, K. W. K. mTOR Signalling in Diabetic Peripheral Neuropathy: Balancing Neuropathic Pain and Schwann Cell-Mediated Repair. Regenerative Medicine and Dentistry 2026, 3 (1), 2. https://doi.org/10.53941/rmd.2026.100002.
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