• R A Warwick and M Hanani.
• Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
• Eur J Pain. 2013 Apr 1;17(4):571-80.

BackgroundChemotherapy-induced peripheral neuropathy is a serious side effect in cancer treatment, a major manifestation being neuropathic pain that can be debilitating and can reduce the quality of life of the patient. Oxaliplatin and taxol are common anti-cancer drugs that induce neuropathic pain by an unknown mechanism. We tested the hypothesis that satellite glial cells in dorsal root ganglia (DRGs) are altered in chemotherapy-induced peripheral neuropathy models and contribute to neuropathic pain.MethodsMice were injected with either oxaliplatin or taxol and examined at 7-30 days. Glial fibrillary acidic protein (glial activation marker) expression was determined by immunohistochemistry. Satellite glial cells in isolated DRG were injected with the fluorescent dye Lucifer yellow and the incidence of dye coupling among these cells that surround different neurons was quantified.ResultsTaxol or oxaliplatin increased glial fibrillary acidic protein expression in satellite glial cells. Gap junction-mediated coupling between satellite glial cells was increased by up to fivefold after oxaliplatin and by up to twofold after taxol. This is consistent with work on other pain models showing that augmented satellite glial cell coupling contributes to chronic pain. Administration of the gap junction blocker carbenoxolone to chemotherapy-treated mice produced an analgesic-like effect.ConclusionsWe propose that increased coupling by gap junctions is part of satellite glial cell activation, and that augmented coupling contributes to the lowering of pain threshold in oxaliplatin- and taxol-treated mice. We further propose that gap junction blockers may have potential in treating chemotherapy-induced neuropathic pain.© 2012 European Federation of International Association for the Study of Pain Chapters.

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