title: Cdk5 inhibitor roscovitine alleviates neuropathic pain in the dorsal root ganglia by downregulating N-methyl-D-aspartate receptor subunit 2A.
abstract: Cyclin-dependent kinase 5 (Cdk5) is a member of the small proline-directed serine/threonine kinase family. Cdk5 is not involved in cell cycle regulation, but is implicated in neurodegenerative disorders. However, the role of Cdk5 in neuropathic pain remains unclear. This study aimed to evaluate the possibility that Cdk5 is involved in neuropathic pain in the dorsal root ganglia (DRG). We injected intrathecally Cdk5 inhibitor roscovitine in rat model of chronic compression of dorsal root ganglion and examined pain behaviors and the expression of N-methyl-d-aspartate receptor subunit 2A (NR2A) but not NR2B or NR1 in DRG. We found that roscovitine alleviated neuropathic pain, causing decline in paw withdrawal mechanical threshold and paw withdrawal thermal latency. Furthermore, roscovitine inhibited NR2A expression in DRG. These data suggest that Cdk5-NR2A pathway regulates neuropathic pain in DRG, and intrathecal injection of roscovitine could alleviate neuropathic pain. Our findings provide new insight into the analgesic effects of Roscovitine and identify Cdk5-NR2A pathway as a potential target for effective treatment of neuropathic pain.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000187:drug effects*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D000077546:Roscovitine; D013346:Subarachnoid Space / Q000473:pathology; D013997:Time Factors
chemical_list: D051360:Cyclin-Dependent Kinase 5; D047428:Protein Kinase Inhibitors; D011687:Purines; D016194:Receptors, N-Methyl-D-Aspartate; D000077546:Roscovitine