Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice

Behav Brain Res. 2024 Feb 29:459:114790. doi: 10.1016/j.bbr.2023.114790. Epub 2023 Nov 30.


Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Keywords: ALA; CPIP; Chronic pain; NADPH oxidase; Oxidative stress; Thioctic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Pain*
  • Disease Models, Animal
  • Hydrogen Peroxide
  • Hyperalgesia
  • Ischemia
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NADPH Oxidases / therapeutic use
  • Neuroinflammatory Diseases
  • Nociception
  • Oxidative Stress
  • Reflex Sympathetic Dystrophy* / complications
  • Reflex Sympathetic Dystrophy* / drug therapy
  • Superoxide Dismutase
  • Thioctic Acid* / pharmacology


  • Thioctic Acid
  • prostaglandin-inositol cyclic phosphate
  • Hydrogen Peroxide
  • NADPH Oxidases
  • Superoxide Dismutase