Denis R Clohisy1, Patrick W Mantyh. 1. Department of Orthopedic Surgery and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. clohi001@tc.umn.edu
Abstract
BACKGROUND: Bone cancer pain is very common, and patients with this type of pain may be difficult to treat. Development of an experimental model for studying this condition is critical to advancing an understanding of the mechanisms that cause pain in patients with malignant disease. METHODS: A murine model of bone cancer was studied. Combined analysis of the extent of tumor-induced bone destruction, pain, and neurochemical characterization of the peripheral and central nervous systems was performed to investigate bone cancer pain. Disease-induced bone destruction was assessed by radiographs and histomorphometry. Pain was assessed by spontaneous and elicited behaviors, and neurochemical analysis involved immunohistochemical detection of hyperalgesic peptides and neurochemical markers. RESULTS: Mice with distal femoral sarcomas exhibited behavioral and neurochemical measures of pain. The pain condition created by malignant bone disease was distinct neurochemically from inflammatory and neuropathic pain states. Experimental evidence indicated that both disease-induced osteolysis and tumors themselves contributed to the generation of pain and that peripheral and central sensitization of the nervous system was present. CONCLUSIONS: Malignant bone disease creates a unique pain state that involves sensitization of the nervous system. Major contributors to the pain state within the bone tissue are osteoclastic bone resorption and the malignant disease itself. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11144
BACKGROUND:Bone cancer pain is very common, and patients with this type of pain may be difficult to treat. Development of an experimental model for studying this condition is critical to advancing an understanding of the mechanisms that cause pain in patients with malignant disease. METHODS: A murine model of bone cancer was studied. Combined analysis of the extent of tumor-induced bone destruction, pain, and neurochemical characterization of the peripheral and central nervous systems was performed to investigate bone cancer pain. Disease-induced bone destruction was assessed by radiographs and histomorphometry. Pain was assessed by spontaneous and elicited behaviors, and neurochemical analysis involved immunohistochemical detection of hyperalgesic peptides and neurochemical markers. RESULTS:Mice with distal femoral sarcomas exhibited behavioral and neurochemical measures of pain. The pain condition created by malignant bone disease was distinct neurochemically from inflammatory and neuropathic pain states. Experimental evidence indicated that both disease-induced osteolysis and tumors themselves contributed to the generation of pain and that peripheral and central sensitization of the nervous system was present. CONCLUSIONS:Malignant bone disease creates a unique pain state that involves sensitization of the nervous system. Major contributors to the pain state within the bone tissue are osteoclastic bone resorption and the malignant disease itself. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11144