Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn

Chang, Yu-Wen; Tan, Andrew; Saab, Carl; Waxman, Stephen

doi:10.1016/j.jpain.2009.06.009

« Previous Next »The Journal of Pain
Volume 11, Issue 2 , Pages 119-130, February 2010

Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn

Yu-Wen Chang
- Department of Neurology and Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, and Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut
Andrew Tan
- Department of Neurology and Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, and Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut
Carl Saab
- Department of Surgery, Rhode Island Hospital, Brown Alpert Medical School and Department of Neuroscience, Brown University, Providence, Rhode Island
Stephen Waxman
- Department of Neurology and Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, and Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut
- Address reprint requests to Dr. Stephen G. Waxman, Chairman, Dept. of Neurology, Yale University School of Medicine, 333 Cedar Street, LCI-707, New Haven, CT 06510.

Received 6 May 2009; received in revised form 15 June 2009; accepted 17 June 2009. published online 10 September 2009.

Abstract

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.

Perspective

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.

Key words: Burn injury, allodynia, hyperexcitability, neuropathic pain, microglia