A threshold problem! Most DRG Sensory Neurons Are Modality-Specific, Not Polymodal

lfqueme · January 24, 2017, 3:48pm

ncbi.nlm.nih.gov

In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP.

EC Emery, AP Luiz, S Sikandar, R Magnúsdóttir, X Dong and JN Wood, Science advances, Nov 2016

Mechanistic insights into pain pathways are essential for a rational approach to treating this vast and increasing clinical problem. Sensory neurons that respond to tissue damage (nociceptors) may evoke pain sensations and are typically classified on the basis of action potential velocity. Electrophysiological studies have suggested that most of the C-fiber nociceptors are polymodal, responding to a variety of insults. In contrast, gene deletion studies in the sensory neurons of transgenic mice have frequently resulted in modality-specific deficits. We have used an in vivo imaging approach using the genetically encoded fluorescent calcium indicator GCaMP to study the activity of dorsal root ganglion sensory neurons in live animals challenged with painful stimuli. Using this approach, we can visualize spatially distinct neuronal responses and find that >85% of responsive dorsal root ganglion neurons are modality-specific, responding to either noxious mechanical, cold, or heat stimuli. These observations are mirrored in behavioral studies of transgenic mice. For example, deleting sodium channel Nav1.8 silences mechanical- but not heat-sensing sensory neurons, consistent with behavioral deficits. In contrast, primary cultures of axotomized sensory neurons show high levels of polymodality. After intraplantar treatment with prostaglandin E2, neurons in vivo respond more intensely to noxious thermal and mechanical stimuli, and additional neurons (silent nociceptors) are unmasked. Together, these studies define polymodality as an infrequent feature of nociceptive neurons in normal animals.

Have you seen the ongoing discussion?

As a disclaimer, I consider myself part of the church of the polymodal afferent, thus I found the results difficult to digest.

What has come to my attention is that on the Emery paper they used a 2g VFH to mechanically stimulate the receptive field and evaluate polymodality. What is your experience in naive-skin electrophysiology? Do all your mechanically sensitive neurons have thresholds below 2g? Mine sure don’t. In fact I tend to find a large population of C fibers that have thresholds even above 4 grams. Did they just miss a huge part of the polymodal population because they did not use a stronger von Frey? Would that explain their discrepancy with the Woodbury paper where they used ascending forces up to 500mN (~50g)?

What do you guys think? Tag your electrophysiologist, I look forward to hearing your opinions.

@fmoehring @achamess

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A threshold problem! Most DRG Sensory Neurons Are Modality-Specific, Not Polymodal

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