Capsaicin-sensitive sensory nerve fibers contribute to the generation and maintenance of skeletal fracture pain

J. M. Jimenez-Andrade, A. P. Bloom, W. G. Mantyh, N. J. Koewler, K. T. Freeman, D. Delong, J. R. Ghilardi, M. A. Kuskowski, P. W. Mantyh

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1244-1254
Number of pages11
Issue number4
StatePublished - Sep 15 2009


  • analgesics
  • bone healing
  • orthopedic
  • periosteum

ASJC Scopus subject areas

  • General Neuroscience


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