Senescence‐Associated Cdkn1a (p21) Is Upregulated in Rodent Dorsal Root Ganglion Neurons Across Lesion‐Based Neuropathic Pain Models
Philipp N. Ostermann, Rebecca Dinnendahl, Jörg Isensee, Tim HuchoBackground
Senescence of peripheral sensory neurons has recently been associated with increased nociceptive signalling and pain chronification. Whether increased expression of senescence‐associated genes is found across pain conditions and independent study settings remains to be investigated.
Methods
We analysed 20 publicly available whole‐genome transcriptome data sets on rodent dorsal root ganglion (DRG) tissue and focused on Cdkn1a (p21) and Cdkn2a (p16) expression levels as two widely used senescence markers in different pain models.
Results
We found that Cdkn1a but not Cdkn2a RNA expression exhibited a robust recurrent significant increase in different axotomy‐ and lesion‐based neuropathic pain models but not in other pain models, including inflammatory pain. Data from one study including male and female rats indicated a potential sex‐dependent effect of Cdkn1a upregulation following nerve injury, which warrants further investigation. Overall, Cdkn1a RNA levels were increased among all DRG neuronal subtypes, seemed to have reached their maximum three to 7 days following nerve injury and remained elevated in some neurons as long as 60 days post‐injury.
Conclusions
Cdkn1a upregulation in DRG neurons is a widespread response to nerve injury that is found across independent study settings.