| First Author | Lezgiyeva K | Year | 2026 |
| Journal | Neuron | PubMed ID | 42398504 |
| Mgi Jnum | J:389447 | Mgi Id | MGI:8376815 |
| Doi | 10.1016/j.neuron.2026.06.014 | Citation | Lezgiyeva K, et al. (2026) Fast-conducting mechanonociceptors uniquely engage reflexive and affective pain circuitry to drive protective responses. Neuron |
| abstractText | Nociceptors detect damaging stimuli and evoke pain in healthy animals. We conducted an optogenetic activation screen to identify genetically defined nociceptor populations that elicit place aversion and nocifensive behaviors in response to stimulation. Smr2(Cre)- and Bmpr1b(Cre)-labeled Adelta high-threshold mechanoreceptors (HTMRs) emerged as two of the few nociceptor populations, and we focused on investigating their physiological, morphological, functional, and synaptic properties. These neurons densely innervate skin and other organs, are activated only by intense, potentially damaging stimuli, and are necessary for protective responses to sharp mechanical stimuli. Centrally, Adelta-HTMR projections span multiple spinal segments and terminate across spinal cord laminae, forming strong, monosynaptic connections onto anterolateral tract projection neurons, including antenna cells of the deep dorsal horn. Adelta-HTMRs also engage a local spinal reflex circuit, enabling a remarkably rapid limb withdrawal. Thus, Adelta-HTMRs are myelinated nociceptors with unique properties that can be exploited for the development of new analgesics. |
