A mechanism-based understanding of bone cancer pain.
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.
Mantyh
Patrick W
PW
Neurosystems Center, Department of Preventive Sciences, University of Minnesota, 18-208 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
D000138:Acidosis / Q000209:etiology / Q000503:physiopathology; D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D001842:Bone and Bones; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009619:Nociceptors / Q000503:physiopathology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D011522:Protons
C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011522:Protons; D020932:Nerve Growth Factor