Traumatic peripheral nerve injuries are at high risk of neuropathic pain and novel, effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. The most common traumatic nerve injuries seen clinically are those resulting in axonotmesis (i.e. crush), yet the neuropathic phenotype of ‘painful’ nerve crush injuries remain poorly understood. 

We report the neuropathology and sensory symptoms of a focal nerve crush using custom-modified hemostats resulting in either complete (‘full’) or incomplete (‘partial’) axonotmesis in adult mice.  Assays of thermal and mechanically-evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. 

In both crush models, motor function was equally affected early after injury; in contrast, partial crush of the nerve resulted in the early return of pin-prick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, that was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers (IENF), fewer dorsal root ganglia (DRG) expressing the injury marker ATF3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness.

In summary, the escape of small-diameter axons from Wallerian degeneration is a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.