Clohisy Denis R, Mantyh Patrick W
Department of Orthopedic Surgery and Cancer Center, University of Minnesota, 420 Delaware Street SE, MMC 492, Minneapolis, MN 55455, USA.
Clin Orthop Relat Res. 2003 Oct(415 Suppl):S279-88. doi: 10.1097/01.blo.0000093059.96273.56.
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.
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.
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.
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.
骨癌疼痛非常常见，患有这种疼痛的患者可能难以治疗。开发一种用于研究这种情况的实验模型对于增进对恶性疾病患者疼痛产生机制的理解至关重要。
对一种骨癌小鼠模型进行了研究。对肿瘤引起的骨破坏程度、疼痛以及外周和中枢神经系统的神经化学特征进行联合分析，以研究骨癌疼痛。通过X线片和组织形态计量学评估疾病引起的骨破坏。通过自发和诱发行为评估疼痛，神经化学分析包括对痛觉过敏肽和神经化学标志物的免疫组织化学检测。
患有股骨远端肉瘤的小鼠表现出疼痛的行为和神经化学指标。恶性骨病产生的疼痛状况在神经化学上与炎症性和神经性疼痛状态不同。实验证据表明，疾病引起的骨溶解和肿瘤本身都导致了疼痛的产生，并且存在神经系统的外周和中枢敏化。
恶性骨病会产生一种独特的疼痛状态，涉及神经系统的敏化。骨组织内疼痛状态的主要促成因素是破骨细胞性骨吸收和恶性疾病本身。
