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

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)-1 alpha and their relationship with pain sensitivity under hypoxia. 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-1 alpha in cortex were analyzed by real-time PCR and Western blotting. HIF-1 alpha 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. CIH decreases pain sensitivity in rats, possibly through activating HIF-1 alpha and increasing MOR and DOR expression.