Unilateral focal burn injury is followed by long-lasting bilateral allodynia and neuronal hyperexcitability in spinal cord dorsal horn.
Pain after burn injury can be intense and long lasting. Treatment is often ineffective, and there is a need for increased knowledge of the underlying pain mechanisms. In the present study, we established a unilateral partial-thickness burn injury model, which produces ipsilateral mechanical allodynia soon after injury, followed by contralateral allodynia. Chronic bilateral allodynia lasts up to 8 weeks postinjury in this model. In addition to the change in pain behavior, electrophysiological analyses showed that dorsal horn neurons become hyperexcitable and display significantly increased evoked activity with enlarged receptive fields, initially on the side ipsilateral to the injury, and subsequently on both sides of the spinal cord. It is known that, following nerve injury, activation of p38 mitogen-activated protein kinase (MAPK) pathways within spinal microglia contributes to the pathogenesis of pain. In our burn injury model, rapid and prolonged activation of phospho-p38-expressing microglia occurs bilaterally in the spinal cord dorsal horn. Taken together, these data demonstrate that a unilateral peripheral burn injury can produce long-lasting allodynia that can spread to the contralateral limb, together with dorsal horn neuronal hyperexcitability and microglial activation on both ipsilateral and contralateral sides of the spinal cord. Our results suggest that central neuropathic mechanisms can contribute to pain after burn injury.


CONCLUSIONS
Mechanisms contributing to pain following burn injury are incompletely understood. In a novel animal model of burn injury, we have demonstrated hyperexcitability of second-order sensory neurons, activation of microglia, and chronic bilateral pain following the burn injury. This work identifies potential therapeutic targets to alleviate pain after burn injury.
Chang
Yu-Wen
YW
Department of Neurology and Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
Tan
Andrew
A
Saab
Carl
C
Waxman
Stephen
S
D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology*; D006941:Hyperesthesia / Q000209:etiology*; D008297:Male; D017628:Microglia / Q000502:physiology; D010146:Pain; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D013116:Spinal Cord / Q000473:pathology*; D013373:Substance P / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D039481:CD11b Antigen; D013373:Substance P; D048051:p38 Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide