Changes in the circadian rhythm of mRNA expression for µ-opioid receptors in the periaqueductal gray under a neuropathic pain-like state.

Abstract

Variation in the production of opioid receptors over a 24-h period is considered to contribute to circadian alterations in neuropathic pain. In this study, we investigated the possible changes in the circadian rhythm of mRNA expression for µ-opioid receptor (MOR), κ-opioid receptor (KOR), and adrenaline α2a receptor (α2a) in the periaqueductal gray, frontal cortex, thalamus, and spinal cord following sciatic nerve ligation in mice. In sham-operated mice, the latencies of hind paw-withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly greater than that at 8:00 and the latency at 2:00 was significantly less than those at 14:00 and 20:00, indicating a "rest" period-dominant circadian rhythm for thermal pain-thresholds. In sciatic nerve-ligated mice, the latencies of hind paw-withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly less than that at 8:00, and the latency at 2:00 was significantly greater than those at 14:00 and 20:00. A correlative tendency between the time-variation of pain latency and the time-variation of MOR mRNA expression was observed in the periaqueductal gray of sham-operated and sciatic nerve-ligated mice. In contrast, neither mouse showed a strong circadian rhythm for the expressions of KOR and α2a mRNAs in any region. The present data suggest that changes in MOR mRNA expression in the periaqueductal gray may be synchronized with the circadian rhythm for the pain threshold for noxious thermal stimuli. In contrast, neuropathic pain in mice exhibited a negative circadian pattern for the expression of MOR, KOR, and α2a receptors in the frontal cortex, thalamus, and spinal cord.