The contribution of satellite glial cells to chemotherapy-induced neuropathic pain.
BACKGROUND
Chemotherapy-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.


METHODS
Mice 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.


RESULTS
Taxol 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.


CONCLUSIONS
We 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.
Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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RA
Warwick
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Hanani
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002229:Carbenoxolone / Q000494:pharmacology / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000633:toxicity*; D017288:Pain Threshold / Q000187:drug effects; D027161:Satellite Cells, Perineuronal / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D005904:Glial Fibrillary Acidic Protein; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002229:Carbenoxolone; D017239:Paclitaxel