» Articles » PMID: 19129394

Persistent Pain is Dependent on Spinal Mitochondrial Antioxidant Levels

Overview
Journal J Neurosci
Specialty Neurology
Date 2009 Jan 9
PMID 19129394
Citations 73
Authors
Affiliations
Soon will be listed here.
Abstract

Reactive oxygen species (ROS) scavengers have been shown to relieve persistent pain; however, the mechanism is not clearly understood. Superoxide produced from mitochondrial oxidative phosphorylation is considered the major source of ROS in neurons during excitation where mitochondrial superoxide levels are normally controlled by superoxide dismutase (SOD-2). The present study hypothesizes that capsaicin-induced secondary hyperalgesia is a consequence of superoxide build-up in spinal dorsal horn neurons and SOD-2 is a major determinant. To test this hypothesis, the spinal levels of SOD-2 activity, inactivated SOD-2 proteins, and mitochondrial superoxide were measured and correlated to the levels of capsaicin-induced secondary hyperalgesia in mice with and without SOD-2 manipulations. The data suggest that superoxide accumulation is a culprit in the abnormal sensory processing in the spinal cord in capsaicin-induced secondary hyperalgesia. Our studies also support the notion that SOD-2 nitration is a critical mechanism that maintains elevated superoxide levels in the spinal cord after capsaicin treatment. Finally, our findings suggest a therapeutic potential for the manipulation of spinal SOD-2 activity in pain conditions.

Citing Articles

Decoding the mechanism of proanthocyanidins in central analgesia: redox regulation and KCNK3 blockade.

Gu J, Wang J, Fan H, Wei Y, Li Y, Ma C Exp Mol Med. 2025; .

PMID: 40025170 DOI: 10.1038/s12276-025-01412-5.


18 kDa Translocator protein (TSPO) is upregulated in rat brain after peripheral nerve injury and downregulated by diroximel fumarate.

Cazuza R, Zagrai S, Grieco A, Avery T, Abell A, Wey H Brain Behav Immun. 2024; 123:11-27.

PMID: 39218234 PMC: 11624078. DOI: 10.1016/j.bbi.2024.08.057.


Crosstalk of Mast Cells and Natural Killer Cells with Neurons in Chemotherapy-Induced Peripheral Neuropathy.

Yun H, Goel Y, Gupta K Int J Mol Sci. 2023; 24(16).

PMID: 37628724 PMC: 10454469. DOI: 10.3390/ijms241612543.


Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.

Hu Y, Liu J, Zhuang R, Zhang C, Lin F, Wang J Cell Mol Neurobiol. 2023; 43(7):3343-3373.

PMID: 37470889 PMC: 11410024. DOI: 10.1007/s10571-023-01389-7.


Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.

Zhou S, Pan Y, Zhang Y, Gu L, Ma L, Xu Q Korean J Pain. 2023; 36(3):316-327.

PMID: 37183652 PMC: 10322665. DOI: 10.3344/kjp.22398.


References
1.
Gorg B, Wettstein M, Metzger S, Schliess F, Haussinger D . Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat. Hepatology. 2005; 41(5):1065-73. DOI: 10.1002/hep.20662. View

2.
Adwanikar H, Karim F, Gereau 4th R . Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation. Pain. 2004; 111(1-2):125-35. DOI: 10.1016/j.pain.2004.06.009. View

3.
Lee I, Kim H, Kim J, Chung K, Chung J . The role of reactive oxygen species in capsaicin-induced mechanical hyperalgesia and in the activities of dorsal horn neurons. Pain. 2007; 133(1-3):9-17. PMC: 2225450. DOI: 10.1016/j.pain.2007.01.035. View

4.
Tal M . A novel antioxidant alleviates heat hyperalgesia in rats with an experimental painful peripheral neuropathy. Neuroreport. 1996; 7(8):1382-4. DOI: 10.1097/00001756-199605310-00010. View

5.
Sluka K, Rees H, Chen P, Tsuruoka M, Willis W . Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate. Exp Brain Res. 1997; 115(1):15-24. DOI: 10.1007/pl00005675. View