Neuropathic pain caused by miswiring and abnormal end organ targeting

This paper describes a remarkable link between reinnervation after peripheral nerve damage and painful hypersensitivity to gentle touch or mechanical allodynia.
Using spared nerve injury as a model peripheral nerve injury combined with genetically labeling of neurons detecting noxious stimuli (nociceptors) and gentle touch (low-threshold mechanoreceptors), the authors studied neural regrowth using non-invasive imaging and pain-related behavior for up to 42 weeks after damage.
They found that nociceptors sprouting from the spared nerve are responsible for painful hypersensitivity to low gentle touch in the re-innervated territory.
These fibers show irregular terminal connectivity in the skin and lower activation thresholds, providing the neural basis for reinnervation-induced mechanical allodynia in denervated regions.
Authors
Vijayan Gangadharan, Hongwei Zheng, Francisco J. Taberner, Jonathan Landry, Timo A. Nees, Jelena Pistolic, Nitin Agarwal, Deepitha Männich, Vladimir Benes, Moritz Helmstaedter, Björn Ommer, Stefan G. Lechner, Thomas Kuner & Rohini Kuner.