Jimenez-Andrade J M, Bloom A P, Mantyh W G, Koewler N J, Freeman K T, Delong D, Ghilardi J R, Kuskowski M A, Mantyh P W
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Neuroscience. 2009 Sep 15;162(4):1244-54. doi: 10.1016/j.neuroscience.2009.05.065. Epub 2009 May 29.
Although skeletal pain can have a marked impact on a patient's functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague-Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15-16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP(+)) sensory nerve fibers, but not 200 kDa neurofilament H positive (NF200(+)) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain-related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP(+) C-fibers) and capsaicin-insensitive (primarily NF200(+) A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain.
尽管骨骼疼痛会对患者的功能状态和生活质量产生显著影响，但对于驱动非恶性骨痛的外周神经纤维的特定群体，我们所知甚少。在本报告中，新生雄性Sprague-Dawley大鼠接受辣椒素或赋形剂处理，当动物成年（15 - 16周龄）时造成股骨骨折。辣椒素处理而非赋形剂处理导致骨膜中降钙素基因相关肽阳性（CGRP(+)）感觉神经纤维密度显著降低（>70%），但200 kDa神经丝H阳性（NF200(+)）感觉神经纤维密度未降低。骨膜是一种薄的、细胞性和纤维性组织，紧密附着于除关节面外的所有骨的外表面，似乎在驱动骨折疼痛中起关键作用。在用辣椒素处理而非赋形剂处理的动物中，通过自发退缩、警戒和负重测量的骨折诱导的骨骼疼痛相关行为的严重程度降低了50%，但时间进程没有变化。这些结果表明，对辣椒素敏感的（主要是CGRP(+) C纤维）和对辣椒素不敏感的（主要是NF200(+) A - δ纤维）感觉神经纤维都参与驱动骨骼骨折疼痛。骨骼疼痛可能是创伤性骨折、骨质疏松性骨折以及膝关节和髋关节置换等骨科手术后功能恢复的重大障碍。了解需要靶向抑制骨骼疼痛产生和维持的感觉神经纤维的特定群体，可能有助于开发更具特异性的基于机制的疗法，从而有效减轻急性和慢性骨骼疼痛。
