Mitotoxicity in distal symmetrical sensory peripheral neuropathies

Nat Rev Neurol. 2014 Jun;10(6):326-36. doi: 10.1038/nrneurol.2014.77. Epub 2014 May 20.

Abstract

Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor--that is, intraepidermal nerve fibres--of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / adverse effects
  • Antineoplastic Agents / adverse effects
  • Diabetes Complications
  • Disease Models, Animal
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Neuralgia / physiopathology
  • Peripheral Nervous System Diseases / etiology
  • Peripheral Nervous System Diseases / pathology*
  • Peripheral Nervous System Diseases / physiopathology

Substances

  • Anti-HIV Agents
  • Antineoplastic Agents