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.