| First Author | Khoutorsky A | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 42 | Pages | 11949-11954 |
| PubMed ID | 27698114 | Mgi Jnum | J:238493 |
| Mgi Id | MGI:5822941 | Doi | 10.1073/pnas.1614047113 |
| Citation | Khoutorsky A, et al. (2016) eIF2alpha phosphorylation controls thermal nociception. Proc Natl Acad Sci U S A 113(42):11949-11954 |
| abstractText | A response to environmental stress is critical to alleviate cellular injury and maintain cellular homeostasis. Eukaryotic initiation factor 2 (eIF2) is a key integrator of cellular stress responses and an important regulator of mRNA translation. Diverse stress signals lead to the phosphorylation of the alpha subunit of eIF2 (Ser51), resulting in inhibition of global protein synthesis while promoting expression of proteins that mediate cell adaptation to stress. Here we report that eIF2alpha is instrumental in the control of noxious heat sensation. Mice with decreased eIF2alpha phosphorylation (eIF2alpha+/S51A) exhibit reduced responses to noxious heat. Pharmacological attenuation of eIF2alpha phosphorylation decreases thermal, but not mechanical, pain sensitivity, whereas increasing eIF2alpha phosphorylation has the opposite effect on thermal nociception. The impact of eIF2alpha phosphorylation (p-eIF2alpha) on thermal thresholds is dependent on the transient receptor potential vanilloid 1. Moreover, we show that induction of eIF2alpha phosphorylation in primary sensory neurons in a chronic inflammation pain model contributes to thermal hypersensitivity. Our results demonstrate that the cellular stress response pathway, mediated via p-eIF2alpha, represents a mechanism that could be used to alleviate pathological heat sensation. |
