Downregulation of the spinal dorsal horn clock gene Per1 expression leads to mechanical hypersensitivity via c-jun N-terminal kinase and CCL2 production in mice

Publication date: Available online 23 January 2016 Source:Molecular and Cellular Neuroscience Author(s): Norimitsu Morioka, Munenori Saeki, Tatsuhiko Sugimoto, Takuya Higuchi, Fang Fang Zhang, Yoki Nakamura, Kazue Hisaoka-Nakashima, Yoshihiro Nakata Disturbances of circadian rhythm and dysregulation of clock gene expression are involved in the induction of various neurological disorder states, including chronic pain. However, the relationship between the CNS circadian-clock gene system and nociception remains poorly defined. Significant circadian oscillations of Period (Per1, Per2), Bmal1 and Cryptochrome 1 (Cry1) mRNA expression have been observed in the lumbar spinal dorsal horn of naïve mice. The current study examined the expression of clock genes in the lumbar spinal dorsal horn of mice with neuropathic pain due to a partial sciatic nerve ligation (PSNL). Seven days after PSNL, the mice displayed a robust unilateral hind paw mechanical hypersensitivity. The normal circadian oscillations of Per1, Per2 and Cry1, but not Bmal1, mRNA expression were significantly suppressed in the ipsilateral lumbar spinal dorsal horn of PSNL mice 7days following surgery. The circadian expression of PER1 protein, in particular, was also significantly suppressed in the ipsilateral spinal dorsal horn of PSNL mice. Double-labeling immunohistochemistry revealed downregulation of PER1 in neurons and astrocytes, but not microglia. Knockdown of Per1 expression by intrathecal tr...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research