Journal
ANESTHESIOLOGY
Volume 116, Issue 2, Pages 415-431Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e318242a801
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Funding
- National Science Council, Taipei, Taiwan [NSC 96-2320-B-030-007-MY2, NSC 98-2320-B-030-002-MY3]
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Background: Neuroprotective effects of hypothermia on peripheral nerve injury remain uncertain. This study investigated the efficacy of hypothermia in attenuating neuropathic pain and glial activation in the cuneate nucleus in a median nerve chronic constriction injury (CCI) model. Methods: Sprague-Dawley rats (n = 246) that underwent median nerve ligature at the elbow received various degrees of regional and whole-body hypothermia 15 min before CCI and 5 h, 1, 3, and 5 days after CCI. Hypothermia was maintained for 4 h. Seven days after CCI, behavioral and electro-physiological testings were conducted. Immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analysis of glial activation and measuring pro-inflammatory cytokines, respectively. Results: Mild (32 degrees C) and deep (28 degrees C) regional hypothermia administered preinjury and 5 h postinjury attenuated neuropathic pain and glial activation. Application of whole-body hypothermia preinjury and 5 h postinjury provided a similar therapeutic effect. However, whole-body hypothermia, but not regional hypothermia, applied 1, 3, and 5 days postinjury attenuated glial activation and neuropathic pain. Similarly, on days 1,3, and 5 postinjuiy, only whole-body hypothermia was effective in decreasing proinflammatory cytokine levels. The increase in injury discharge observed after CCI could be suppressed by regional or whole-body hypothermia at different stages of nerve injury. Conclusions: At the early stage following nerve injury, regional and whole-body hypothermia suppresses ectopic discharges, and consequently inhibits glial activation and neuropathic pain. At the later stage, pain processing is mediated mainly by cytokines released from activated microglia; therefore, only wholebody hypothermia is effective in modulating pain.
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