Thermal and mechanical modalities converge in the noxious range

There are competing theories on how nociceptive input is encoded by sensory fibers. That sensory modalities are exclusively conveyed by distinct populations of fibers is supported by ablation studies, indicating that TRPV1 ⁺ and MrgprD ⁺ afferents selectively encode for heat and mechanical input, respectively. However, interpreting ablation results can be clouded by compensatory plasticity. Furthermore, a population-level parametric analysis of afferent response profiles to natural stimuli in vivo is still scarce. Using functional imaging in vivo in mice, we found that most TRPV1 ⁺ neurons responded to noxious heat, but not cooling. While none of them responded to innocuous mechanical input, about half were also sensitive to noxious mechanical stimuli. In contrast, 80% of MrgprD ⁺ neurons responded to noxious mechanical stimuli. Yet, 70% were also sensitive to noxious thermal stimuli. Of innocuous mechanosensitive MrgprD ⁺ neurons, <15% responded to innocuous warming and none to innocuous cooling. Polymodality in the innocuous thermal and mechanical range also occurred in <10% of all primary afferents. Acute silencing of TRPV1 ⁺ or MrgprD ⁺ afferents inhibited both thermal and mechanical nociception. In contrast, ablation did not reproduce a combined loss of sensitivity, which appeared to be due to compensatory central disinhibition. Our findings reveal that modality separation dominates in the innocuous regime, while polymodality predominates in the noxious range.