| First Author | Deng L | Year | 2023 |
| Journal | Neuron | Volume | 111 |
| Issue | 17 | Pages | 2642-2659.e13 |
| PubMed ID | 37352856 | Mgi Jnum | J:361897 |
| Mgi Id | MGI:7865972 | Doi | 10.1016/j.neuron.2023.05.024 |
| Citation | Deng L, et al. (2023) Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids. Neuron 111(17):2642-2659.e13 |
| abstractText | Loss-of-function mutations in Nav1.7, a voltage-gated sodium channel, cause congenital insensitivity to pain (CIP) in humans, demonstrating that Nav1.7 is essential for the perception of pain. However, the mechanism by which loss of Nav1.7 results in insensitivity to pain is not entirely clear. It has been suggested that loss of Nav1.7 induces overexpression of enkephalin, an endogenous opioid receptor agonist, leading to opioid-dependent analgesia. Using behavioral pharmacology and single-cell RNA-seq analysis, we find that overexpression of enkephalin occurs only in cLTMR neurons, a subclass of sensory neurons involved in low-threshold touch detection, and that this overexpression does not play a role in the analgesia observed following genetic removal of Nav1.7. Furthermore, we demonstrate using laser speckle contrast imaging (LSCI) and in vivo electrophysiology that Nav1.7 function is required for the initiation of C-fiber action potentials (APs), which explains the observed insensitivity to pain following genetic removal or inhibition of Nav1.7. |
