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Arcourt, Alice; Gorham, Louise; Dhandapani, Rahul; Prato, Vincenzo; Taberner, Francisco J.; Wende, Hagen; Gangadharan, Vijayan; Birchmeier, Carmen; Heppenstall, Paul A.; Lechner, Stefan G.
Neuron (Cambridge, Mass.), 01/2017, Letnik: 93, Številka: 1Journal Article
Painful mechanical stimuli activate multiple peripheral sensory afferent subtypes simultaneously, including nociceptors and low-threshold mechanoreceptors (LTMRs). Using an optogenetic approach, we demonstrate that LTMRs do not solely serve as touch receptors but also play an important role in acute pain signaling. We show that selective activation of neuropeptide Y receptor-2-expressing (Npy2r) myelinated A-fiber nociceptors evokes abnormally exacerbated pain, which is alleviated by concurrent activation of LTMRs in a frequency-dependent manner. We further show that spatial summation of single action potentials from multiple NPY2R-positive afferents is sufficient to trigger nocifensive paw withdrawal, but additional simultaneous sensory input from LTMRs is required for normal well-coordinated execution of this reflex. Thus, our results show that combinatorial coding of noxious and tactile sensory input is required for normal acute mechanical pain signaling. Additionally, we established a causal link between precisely defined neural activity in functionally identified sensory neuron subpopulations and nocifensive behavior and pain. •Identification of an A-fiber nociceptor subpopulation that mediates pinprick pain•Tactile sensory input alleviates A-fiber nociceptor-evoked pain•Tactile sensory input is required for nociceptive reflex coordination•Pinprick-evoked paw withdrawal reflex is triggered independently of firing frequency Arcourt et al. utilize optogenetics to decipher the role of touch receptors and nociceptors in pain signaling. This approach reveals that tactile sensory input has an analgesic effect on acute pain and is required for normal coordination of nocifensive behavior.
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