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.