The Cell and Molecular Basis of Mechanical, Cold, and Inflammatory Pain

TLDR

Peripheral pain pathways are activated by diverse stimuli, and pain behavior correlates with central input from sensory neurons measured electrophysiologically in vivo. The authors ablated all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8 by diphtheria toxin. Mice lacking Nav1.8-expressing neurons displayed normal motor activity and low‑threshold mechanical and acute heat responses but were insensitive to noxious mechanical pressure, cold, and inflammatory pain, whereas nerve injury produced heightened pain sensitivity indistinguishable from normal littermates, demonstrating that Nav1.8 neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.

Abstract

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.