Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

William Olson,Wenqin Luo,Justin Burdge,Minghong Ma,Lian Cui,Tobias Raabe,Ishmail Abdus-Saboor

doi:10.7554/elife.29507

Abstract

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprdCreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd+ nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

Highlights

The skin mediates physical contact with environmental mechanical, thermal, and chemical stimuli
Like the human skin biopsy results, we found that Mas-related gene product receptor D (MrgprD)+ neurites have a 88 comparatively low neurite density in plantar paw compared to trunk skin
We found that ChR2-EYFP+ dorsal root ganglia (DRG) neurons bind IB4 but do not express CGRP24 (Figure 1C), and ChR2-EYFP+ dorsal horn (DH) terminals overlap with IB4 but not CGRP (Figure 1G)

Summary

Introduction

The skin mediates physical contact with environmental mechanical, thermal, and chemical stimuli. Two mechanisms in the peripheral organization of the discriminative touch system facilitate high spatial acuity sensation in the primate distal limbs and mouse whisker pad These are the high innervation density and smaller receptive field sizes of the primary light touch neurons, the A mechanoreceptors, in these regions[1,2,3,4,5,6,7]. We generated a novel MrgprDCreERT2 mouse line to perform systematic sparse genetic tracing of a population of non-peptidergic nociceptors that mediate mechanical pain and beta-alanine (B-AL) triggered itch[22, 23] We chose these nociceptors because they are the most abundant type of cutaneous nociceptor and they likely correspond to the main type of free nerve terminals stained with anti-PGP9.5 antibody in previous human skin biopsy data[9, 24]

Methods

Results

Conclusion