Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia

Pain. 2007 Jan;127(1-2):109-20. doi: 10.1016/j.pain.2006.08.008. Epub 2006 Sep 25.


Cyclin-dependent kinase 5 (Cdk5) is a unique member of the CDK family. It is predominantly expressed in postmitotic neurons and has been implicated in neuronal plasticity. The present study showed that Cdk5 and p35 were expressed in primary sensory and dorsal horn neurons, while p25, an N-terminal truncated derivative of p35, could only be detected in the dorsal horn neurons. Importantly, in the case of control rats, the p35 protein level was much higher in small- and medium-diameter DRG neurons than it was in large neurons. Following CFA injection, Cdk5 activity was upregulated in both primary sensory and dorsal horn neurons. Cdk5 activation in DRG neurons required p35, whereas p25 was required in the dorsal horn. Intrathecal pretreatment with Roscovitine, a specific inhibitor of Cdk5 activity, and intrathecal delivery of the DN-Cdk5(N144) gene both alleviated CFA-induced heat hyperalgesia but not mechanical allodynia. In contrast, overexpression of Cdk5, p35 or p25 in primary sensory and dorsal horn neurons significantly enhanced heat hyperalgesia. We conclude that Cdk5/p35 and Cdk5/p25 complexes in primary sensory and dorsal horn neurons may potentially be involved in nociceptive transmission after inflammation and may be employed in synaptic plasticity underlying pain hypersensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 5 / metabolism*
  • Enzyme Activation
  • Hot Temperature / adverse effects*
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Male
  • Neuritis / etiology
  • Neuritis / physiopathology*
  • Neurons, Afferent / enzymology*
  • Posterior Horn Cells / enzymology*
  • Rats
  • Rats, Sprague-Dawley


  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, rat