Mantyh Patrick W
Neurosystems Center, Department of Preventive Sciences, University of Minnesota, 18-208 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
Novartis Found Symp. 2004;261:194-214; discussion 214-9, 256-61.
Although bone cancer pain can be severe and is relatively common, as it frequently arises from metastases from breast, prostate and lung tumours, relatively little is known about the basic mechanisms that generate and maintain this chronic pain. To begin to define the mechanisms that give rise to bone cancer pain, we developed a mouse model using the intramedullary injection and containment of osteolytic sarcoma cells into the mouse femur. These tumour cells induced bone destruction as well as ongoing and movement evoked pain behaviours similar to that found in patients with bone cancer pain. In addition, there was a significant neurochemical reorganization of sensory neurons that innervate the tumour bearing bone as well as in the spinal cord segments that received sensory input from the cancerous bone. This reorganization generated a neurochemical signature of bone cancer pain that was different from that observed in mouse models of chronic neuropathic or inflammatory pain. These data suggest that there is an inflammatory, neuropathic and tumorigenic component to bone cancer pain. Therefore defining when and how these different components drive bone cancer pain may allow the development of more selective analgesic agents to treat this chronic pain state.
尽管骨癌疼痛可能很严重且相对常见，因为它经常源自乳腺癌、前列腺癌和肺癌的转移，但对于产生和维持这种慢性疼痛的基本机制却知之甚少。为了开始确定引发骨癌疼痛的机制，我们开发了一种小鼠模型，通过将溶骨性肉瘤细胞髓内注射并包埋到小鼠股骨中。这些肿瘤细胞导致了骨破坏以及持续的和运动诱发的疼痛行为，类似于骨癌疼痛患者中发现的情况。此外，支配荷瘤骨的感觉神经元以及从癌性骨接收感觉输入的脊髓节段存在显著的神经化学重组。这种重组产生了骨癌疼痛的神经化学特征，这与在慢性神经性或炎性疼痛小鼠模型中观察到的不同。这些数据表明骨癌疼痛存在炎症、神经病变和致瘤成分。因此，确定这些不同成分何时以及如何驱动骨癌疼痛，可能有助于开发更具选择性的镇痛剂来治疗这种慢性疼痛状态。
