Current Osteoporosis Reports

, Volume 16, Issue 4, pp 325–332 | Cite as

New Insights in Understanding and Treating Bone Fracture Pain

  • Stefanie A. T. Mitchell
  • Lisa A. Majuta
  • Patrick W. MantyhEmail author
Bone and Joint Pain (T King Deeny and S Amin, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Bone and Joint Pain


Purpose of Review

This paper describes recent advances in understanding the mechanisms that drive fracture pain and how these findings are helping develop new therapies to treat fracture pain.

Recent Findings

Immediately following fracture, mechanosensitive nerve fibers that innervate bone are mechanically distorted. This results in these nerve fibers rapidly discharging and signaling the initial sharp fracture pain to the brain. Within minutes to hours, a host of neurotransmitters, cytokines, and nerve growth factor are released by cells at the fracture site. These factors stimulate, sensitize, and induce ectopic nerve sprouting of the sensory and sympathetic nerve fibers which drive the sharp pain upon movement and the dull aching pain at rest. If rapid and effective healing of the fracture occurs, these factors return to baseline and the pain subsides, but if not, these factors can drive chronic bone pain.


New mechanism-based therapies have the potential to fundamentally change the way acute and chronic fracture pain is managed.


Skeletal Nociceptors Nerve growth factor Pediatric Genetic disorders Geriatric 


Funding Information

Research supporting this manuscript was funded by NIH grants CA154550, CA157449, and NS023970 to Patrick Mantyh. Dr. Mantyh has served as a consultant and/or received research grants from Abbott (Abbott Park, IL), Adolor (Exton, PA), Array Biopharma (Boulder, CO), Johnson and Johnson (New Brunswick, NJ), Merck (White Plains, New York), Pfizer (New York, NY), Plexxikon (Berkeley, CA), Rinat (South San Francisco, CA), and Roche (Palo Alto, CA).

Compliance with Ethical Standards

Conflict of Interest

Stefanie Mitchell and Lisa Majuta declare no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


Papers of particular interest, published recently, have been highlighted as: • Of importance ••Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Stefanie A. T. Mitchell
    • 1
  • Lisa A. Majuta
    • 1
  • Patrick W. Mantyh
    • 1
    • 2
    Email author
  1. 1.Department of PharmacologyUniversity of ArizonaTucsonUSA
  2. 2.Cancer CenterUniversity of ArizonaTucsonUSA

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