Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Metabolism
Motor control
Neurodegeneration
Cross-disciplinary subjects
Muscular system
General activity
Mood Disorders
Other disorders
Joints
Central Nervous System (CNS)
Sensory system
Authors
H Wang, X Huo, C Han et al
Lab
Pain Management Center, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China
Journal
Molecular and Cellular Biochemistry
Abstract
Neuropathic pain (NP) is chronic, intractable, and typically not alleviated using analgesics. Ferroptosis is a new type of cell death characterized by mitochondrial damage, oxidative stress, and mitochondrial dysfunction, affecting specific types of synaptic plasticity in the spinal cord. Here, we evaluated the role of ferroptosis in NP using chronic contractile injury (CCI) in rats. The CCI and control groups were subjected to sciatic nerve ligation. The mechanical withdrawal threshold and thermal withdrawal reflex latency were used to detect changes in mechanical pain threshold and thermal pain threshold in rats, respectively. Notably, CCI caused mechanical and thermal stimulation of the injured hind paw, reduced levels of glutathione peroxidase 4 (GPX4), and increased acyl-CoA synthetase long-chain family member 4 (ACSL4). Treatment with the ferroptosis inhibitor ferrostatin-1 (10 mg/kg) 1 h after surgery upregulated GPX4 expression and downregulated ACSL4 expression, whereas the ferroptosis inducer, erastin (10 mg/kg), exerted opposite effects. Treatment with ferrostatin-1 upregulated NeuN expression and downregulated GPX4 expression, whereas erastin reversed these effects. CCI increased the number of damaged mitochondria and decreased the mean planar mitochondrial area, and treatment with erastin further exacerbated these effects. The iron ion content in the spinal cords of CCI-induced rats increased. Treatment with ferrostatin-1 decreased, whereas treatment with erastin increased iron ion content in the CCI-induced rat model. Taken together, our results showed that ferroptosis is involved in the development of NP in male rats by blocking neuron and astrocyte activation in the spinal dorsal horn.
BIOSEB Instruments Used:
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
