Kinesin family member 2A gates nociception

Nociceptive axons undergo remodeling as they innervate their targets during development and in response to environmental insults and pathological conditions. How is nociceptive morphogenesis regulated? Here, we show that the microtubule destabilizer kinesin family member 2A (Kif2a) is a key regulator of nociceptive terminal structures and pain sensitivity. Ablation of Kif2a in sensory neurons causes hyperinnervation and hypersensitivity to noxious stimuli in young adult mice, whereas touch sensitivity and proprioception remain unaffected. Computational modeling predicts that structural remodeling is sufficient to explain the phenotypes. Furthermore, Kif2a deficiency triggers a transcriptional response comprising sustained upregulation of injury-related genes and homeostatic downregulation of highly specific channels and receptors at the late stage. The latter effect can be predicted to relieve the hyperexcitability of nociceptive neurons, despite persisting morphological aberrations, and indeed correlates with the resolution of pain hypersensitivity. Overall, we reveal a critical control node defining nociceptive terminal structure, which is regulating nociception.

Automated summary

This study revealed that the microtubule destabilizer Kif2a plays a crucial role in regulating nociceptive terminal structures and pain sensitivity. Ablation of Kif2a in sensory neurons leads to hyperinnervation and hypersensitivity to noxious stimuli. Additionally, Kif2a deficiency triggers a transcriptional response involving sustained upregulation of injury-related genes and downregulation of specific channels and receptors. Despite the persistent morphological aberrations, the downregulation of channels and receptors can relieve the hyperexcitability of nociceptive neurons and correlates with the resolution of pain hypersensitivity.