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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

4 Issues per year

CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

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Volume 17, Issue 1

Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord

Huiqun Fu / Fenghua Li / Sebastian Thomas / Zhongjin Yang
Published Online: 2017-10-01 | DOI: https://doi.org/10.1016/j.sjpain.2017.08.014


Background and aims

Dysfunction of GABAergic inhibitory controls contributes to the development of neuropathic pain. We examined our hypotheses that (1) chronic constriction injury (CCI)-induced neuropathic pain is associated with increased spinal GABAergic neuron apoptosis, and (2) hyperbaric oxygen therapy (HBO) alleviates CCI-induced neuropathic pain by inhibiting GABAergic neuron apoptosis.


Male rats were randomized into 3 groups: CCI, CCI+HBO and the control group (SHAM). Mechanical allodynia was tested daily following CCI procedure. HBO rats were treated at 2.4 atmospheres absolute (ATA) for 60 min once per day. The rats were euthanized and the spinal cord harvested on day 8 and 14 post-CCI. Detection of GABAergic cells and apoptosis was performed. The percentages of double positive stained cells (NeuN/GABA), cleaved caspase-3 or Cytochrome C in total GABAergic cells or in total NeuN positive cells were calculated.


HBO significantly alleviated mechanical allodynia. CCI-induced neuropathic pain was associated with significantly increased spinal apoptotic GABA-positive neurons. HBO considerably decreased these spinal apoptotic cells. Cytochrome-C-positive neurons and cleaved caspase-3-positive neurons were also significantly higher in CCI rats. HBO significantly decreased these positive cells. Caspase-3 mRNA was also significantly higher in CCI rats. HBO reduced mRNA expression of caspase-3.


CCI-induced neuropathic pain was associated with increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord. HBO alleviated CCI-induced neuropathic pain and reduced GABAergic neuron apoptosis. The beneficial effect of HBO may be via its inhibitory role in CCI-induced GABAergic neuron apoptosis by suppressing mitochondrial apoptotic pathways in the spinal cord.


Increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord is critical in CCI-induced neuropathic pain. The inhibitory role of HBO in GABAergic neuron apoptosis suppresses ongoing neuropathic pain.

Keywords: HBO; CCI-induced neuropathic pain; GABAergic neurons; Spinal cord; Apoptosis


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About the article

Received: 2017-07-27

Accepted: 2017-08-28

Published Online: 2017-10-01

Published in Print: 2017-10-01

Authors’ contributions: ZY designed the experimental protocol. FQconducted the experiments, performed chemical assays, collected and analyzed the data and performed statistical analysis. All authors participated in the experimental processes, data interpretation and manuscript preparation. All authors read and approved the final version of the manuscript.

Funding: This study was supported by the Research Fund of the Department of Anesthesiology, Upstate Medical University, Syracuse, NY, USA.

Ethical issues: All experiments were approved by the Institutional Committee for the Humane Use of Animals, Upstate Medical University. Registration as IACUC#234. All experiments were conducted in accordance with the guidelines established by the National Institutes of Health.

Conflict of interest: None declared.

Citation Information: Scandinavian Journal of Pain, Volume 17, Issue 1, Pages 330–338, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1016/j.sjpain.2017.08.014.

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