Effects of regional and whole-body hypothermic treatment before and after median nerve injury on neuropathic pain and glial activation in rat cuneate nucleus.

Abstract

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 electrophysiological 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°C) and deep (28°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 postinjury, 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 whole-body hypothermia is effective in modulating pain.

• Authors: Yi-Ju Tsai, Chun-Ta Huang, Shih-Chang Lin, Jiann-Horng Yeh
• Journal: Anesthesiology (Anesthesiology) Vol. 116 Issue 2 Pg. 415-31 (Feb 2012) ISSN: 1528-1175 [Electronic] United States
• PMID: 22222476 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Hypothermia, Induced (methods)
• Male
• Median Nerve (injuries, physiopathology)
• Medulla Oblongata (injuries, physiopathology)
• Neuralgia (physiopathology, therapy)
• Neuroglia (metabolism)
• Pain Measurement (methods)
• Rats
• Rats, Sprague-Dawley
• Treatment Outcome