| First Author | He Y | Year | 2016 |
| Journal | J Clin Invest | Volume | 126 |
| Issue | 8 | Pages | 3053-7 |
| PubMed ID | 27348590 | Mgi Jnum | J:237130 |
| Mgi Id | MGI:5811182 | Doi | 10.1172/JCI86165 |
| Citation | He Y, et al. (2016) PKCdelta-targeted intervention relieves chronic pain in a murine sickle cell disease model. J Clin Invest 126(8):3053-7 |
| abstractText | Pain is a life-long symptom in sickle cell disease (SCD) and a predictor of disease progression and mortality, but little is known about its molecular mechanisms. Here, we characterized pain in a targeted knockin mouse model of SCD (TOW mouse) that exclusively expresses human alleles encoding normal alpha- and sickle beta-globin. TOW mice exhibited ongoing spontaneous pain behavior and increased sensitivity to evoked pain compared with littermate control mice expressing normal human hemoglobins. PKCdelta activation was elevated in the superficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory neurons. Functional inhibition and neuron-specific silencing of PKCdelta attenuated spontaneous pain, mechanical allodynia, and heat hyperalgesia in TOW mice. Furthermore, we took a hematopoietic stem cell transplantation approach to generating a SCD model in PKCdelta-deficient mice. Neither spontaneous pain nor evoked pain was detected in the mice lacking PKCdelta despite full establishment of SCD phenotypes. These findings support a critical role of spinal PKCdelta in the development of chronic pain in SCD, which may become a potential target for pharmacological interventions. |
