Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis.

Although nearly 11 million individuals yearly require medical treatment due to burn injuries and develop clinically intractable pain, burn injury-induced pain is poorly understood, with relatively few studies in preclinical models. To elucidate mechanisms of burn injury-induced chronic pain, we utilized a second-degree burn model, which produces a persistent neuropathic pain phenotype. Rats with burn injury exhibited reduced mechanical pain thresholds ipsilateral to the burn injury. Ipsilateral WDR neurons in the spinal cord dorsal horn exhibited hyperexcitability in response to a range of stimuli applied to their hindpaw receptive fields. Because dendritic spine morphology is strongly associated with synaptic function and transmission, we profiled dendritic spine shape, density, and distribution of WDR neurons. Dendritic spine dysgenesis was observed on ipsilateral WDR neurons in burn-injured animals exhibiting behavioral and electrophysiological evidence of neuropathic pain. Heat hyperalgesia testing produced variable results, as expected from previous studies of this model of second-degree burn injury in rats. Administration of Rac1-inhibitor, NSC23766, attenuated dendritic spine dysgenesis, decreased mechanical allodynia and electrophysiological signs of burn-induced neuropathic pain. These results support two related implications: that the presence of abnormal dendritic spines contributes to the maintenance of neuropathic pain, and that therapeutic targeting of Rac1 signaling merits further investigation as a novel strategy for pain management after burn injury.