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Updated: May 4, 2026
Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay
Published on: July 26, 2022
Activation of cyclin-dependent kinase 5 mediates orofacial mechanical hyperalgesia
Michaela Prochazkova, Anita Terse, Niranjana D Amin
1Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. ak40m@nih.gov.
Background:
Cyclin-dependent kinase 5 (Cdk5) is a unique member of the serine/threonine kinase family. This kinase plays an important role in neuronal development, and deregulation of its activity leads to neurodegenerative disorders. Cdk5 also serves an important function in the regulation of nociceptive signaling. Our previous studies revealed that the expression of Cdk5 and its activator, p35, is upregulated in nociceptive neurons during peripheral inflammation. The aim of the present study was to characterize the involvement of Cdk5 in orofacial pain. Since mechanical hyperalgesia is the distinctive sign of many orofacial pain conditions, we adapted an existing orofacial stimulation test to assess the behavioral responses to mechanical stimulation in the trigeminal region of the transgenic mice with either reduced or increased Cdk5 activity.
Results:
Mice overexpressing or lacking p35, an activator of Cdk5, showed altered phenotype in response to noxious mechanical stimulation in the trigeminal area. Mice with increased Cdk5 activity displayed aversive behavior to mechanical stimulation as indicated by a significant decrease in reward licking events and licking time. The number of reward licking/facial contact events was significantly decreased in these mice as the mechanical intensity increased. By contrast, mice deficient in Cdk5 activity displayed mechanical hypoalgesia.
Conclusions:
Collectively, our findings demonstrate for the first time the important role of Cdk5 in orofacial mechanical nociception. Modulation of Cdk5 activity in primary sensory neurons makes it an attractive potential target for the development of novel analgesics that could be used to treat multiple orofacial pain conditions.
Insights
Cyclin-dependent kinase 5 (Cdk5) plays a key role in orofacial pain. Increased Cdk5 activity heightened pain responses, while reduced activity decreased them, suggesting Cdk5 as a potential pain relief target.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Cyclin-dependent kinase 5 (Cdk5) is crucial for neuronal development and function.
- Cdk5 activity is implicated in neurodegenerative disorders and nociceptive signaling.
- Cdk5 and its activator p35 are upregulated in inflamed nociceptive neurons.
Purpose of the Study:
- To investigate the role of Cdk5 in orofacial pain.
- To characterize Cdk5's involvement in mechanical hyperalgesia within the trigeminal region.
Main Methods:
- Utilized transgenic mice with altered Cdk5 activity (overexpressing or lacking p35).
- Assessed behavioral responses to mechanical stimulation in the trigeminal area using an orofacial stimulation test.
- Measured reward licking events and licking time as indicators of pain perception.
Main Results:
- Mice with increased Cdk5 activity showed aversion to mechanical stimulation, with decreased licking events and time.
- Higher mechanical intensity led to a significant reduction in licking events in these mice.
- Mice with reduced Cdk5 activity exhibited mechanical hypoalgesia.
Conclusions:
- Cdk5 is demonstrated to play a significant role in orofacial mechanical nociception.
- Modulating Cdk5 activity in primary sensory neurons presents a potential therapeutic strategy.
- Cdk5 inhibition could lead to novel analgesics for orofacial pain conditions.
