| First Author | Garner KM | Year | 2022 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 323 |
| Issue | 2 | Pages | R227-R243 |
| PubMed ID | 35503781 | Mgi Jnum | J:346555 |
| Mgi Id | MGI:7280996 | Doi | 10.1152/ajpregu.00279.2021 |
| Citation | Garner KM, et al. (2022) The sex-specific role of sensory neuron LKB1 on metabolic stress-induced mechanical hypersensitivity and mitochondrial respiration. Am J Physiol Regul Integr Comp Physiol |
| abstractText | Pain disorders induce metabolic stress in peripheral sensory neurons by reducing mitochondrial output, shifting cellular metabolism, and altering energy use. These processes implicate neuronal metabolism as an avenue for creating novel therapeutics. Liver kinase B1 (LKB1) mediates the cellular response to metabolic stress by inducing the AMPK pathway. The LKB1-AMPK pathway increases energy producing processes, including mitochondrial output. These processes inhibit pain by directly or indirectly restoring energetic balance within a cell. Although the LKB1-AMPK pathway has been linked to pain relief, it is not yet known which cell is responsible for this property, as well any direct ties to cellular metabolism. To elucidate this, we developed a genetic mouse model where LKB1 is selectively removed from Nav1.8-pain sensory neurons and metabolically stressed them by fasting for 24 hours. We found females, but not males, had neuron-specific, LKB1-dependent restoration of metabolic stress-induced mitochondrial metabolism. This was reflected in mechanical hypersensitivity, where the absence of LKB1 led to hypersensitivity in female, but not male, animals. This discrepancy suggests a sex- and cell-specific contribution to LKB1-depdendent fasting-induced mechanical hypersensitivity. While our data represent a potential role for LKB1 in anti-pain pathways in a metabolic-specific manner, more must be done to investigate these sex differences. |
