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Chronic intermittent hypoxia decreases pain sensitivity and increases the expression of HIF1α and opioid receptors in experimental rats

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Abstract

Purpose

The present study was designed to determine the effects of chronic intermittent hypoxia (CIH) on pain sensitivity and the changes in the expression of delta-opioid receptor (DOR), mu-opioid receptor (MOR), and hypoxia-inducible factor (HIF)-1α and their relationship with pain sensitivity under hypoxia.

Methods

CIH was employed to model the low oxygen condition in obstructive sleep apnea (OSA). Normal oxygen condition was used as control. After 1-, 2-, 3-, and 4-week hypoxia, behavioral tests, including paw-withdrawal latency (PWL) and paw-withdrawal threshold (PWT), were performed. The expressions of DOR, MOR and HIF-1α in cortex were analyzed by real-time PCR and Western blotting.

Results

HIF-1α expression was significantly upregulated after 1–4 weeks of hypoxia at both mRNA and protein levels, compared with the controls (P < 0.05). Both PWL and PWT were significantly enhanced in the rats following 3 and 4 weeks of hypoxia (P < 0.05). DOR and MOR expression was significantly upregulated at both mRNA and protein levels after 3 and 4 weeks of hypoxia (P < 0.05), which corresponded to the behavioral changes.

Conclusions

CIH decreases pain sensitivity in rats, possibly through activating HIF-1α and increasing MOR and DOR expression.

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Contributors

All the authors participated in the design of the study. Jian Wu carried out the western blot, rtPCR studies and performed the statistical analysis. Jian Wu and Peng Li were responsible for animal care and carried out the pain sensitivity test. Peng Li participated in the draft the manuscript. All the authors read and approved the final manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, China

    Jian Wu, Xiuying Wu & Weimin Chen

  2. Department of Respiratory Medicine, Shengjing Hospital, China Medical University, Shenyang, China

    Peng Li

Authors
  1. Jian Wu
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  2. Peng Li
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  3. Xiuying Wu
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  4. Weimin Chen
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Corresponding author

Correspondence to Weimin Chen.

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Wu, J., Li, P., Wu, X. et al. Chronic intermittent hypoxia decreases pain sensitivity and increases the expression of HIF1α and opioid receptors in experimental rats. Sleep Breath 19, 561–568 (2015). https://doi.org/10.1007/s11325-014-1047-0

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  • DOI: https://doi.org/10.1007/s11325-014-1047-0

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