Bone Trauma Causes Massive but Reversible Changes in Spinal Circuitry.

Bone fracture with subsequent immobilization of the injured limb can cause complex regional pain syndrome (CRPS) in humans. Mechanisms of CRPS are still not completely understood but bone fracture with casting in mice leads to a similar post-traumatic inflammation as seen in humans and might therefore be an analog to human CRPS. In this article we report behavioral and spinal electrophysiological changes in mice that developed swelling of the paw, warming of the skin, and pain in the injured limb after bone fracture. The receptive field sizes of spinal neurons representing areas of the hind paws increased after trauma and recovered over time-as did the behavioral signs of inflammation and pain. Interestingly, both sides-the ipsi- and the contralateral limb-showed changes in mechanical sensitivity and neuronal network organization after the trauma. The characteristics of evoked neuronal responses recorded in the dorsal horn of the mice were similar between uninjured controls and fractured animals. However, we saw a caudal extension of the represented area of the hind paw in the spinal cord at the injured side and an occurrence of large receptive fields of wide dynamic range neurons. The findings in mice compare with human symptoms in CRPS with ipsi- and also contralateral allodynia and pain. In all mice tested, all signs subsided 12 weeks after trauma. Our data suggest a significant reorganization of spinal circuitry after limb trauma, in a degree more comprehensive than most models of neuropathies. This process seems to be reversible in the rodent.
Perspective: The discovery of enlarged spinal neuronal receptive fields and caudal extension of the representation area of the injured body part, which subsides several weeks after a bone trauma in mice, might give hope to patients of CRPS if-in the future-we are able to translate the rodent recovery mechanisms to post-traumatic humans.
(Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.)