Pathophysiology of bone pain: A review

Haegerstam, Glenn

doi:10.1080/00016470152846682

Cited by 64 publications

(60 citation statements)

References 76 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on the organization of these sensory fibers, along with the clinical picture of painful human fractures [17], the effectiveness of bone stabilization in reducing fracture pain [1,6] and experimental stimulation of human periosteum [9], it is suggested that sensory nerve fibers that innervate the periosteum are uniquely organized to detect mechanical distortion of the periosteum and underlying mineralized bone. It should be noted that sensory fibers in the marrow and mineralized bone may also contribute to the pain following fracture of the skeleton [5,11,18]. Similarly, as sensory neuron mechanotransduction pathways have been shown to be sensitized by nerve growth factor and other compounds released upon tissue injury [12,13], chemical mediators released upon injury to bone probably also participate in driving fracture pain.…”

Section: Cambium Layermentioning

confidence: 99%

Organization of a unique net-like meshwork of CGRP+ sensory fibers in the mouse periosteum: Implications for the generation and maintenance of bone fracture pain

Martin

Jiménez-Andrade

Ghilardi

et al. 2007

Neuroscience Letters

105

View full text Add to dashboard Cite

Although bone fracture frequently results in significant pain and can lead to increased morbidity and mortality, it is still not clearly understood how sensory neurons are organized to detect fracture pain. In the present report we focused on the periosteum, as this thin tissue is highly innervated and tightly adherent to the outer surface of bone. To define the organization and distribution of the sensory and sympathetic fibers in the mouse femoral periosteum, we used whole mount preparations, transverse sections, immunofluoresence, and laser scanning confocal microscopy. While both the outer fibrous layer and the inner more cellular cambium layer of the periosteum receive an extensive innervation by calcitonin gene related peptide (CGRP) and 200-kDa neurofilament (NF200) positive sensory fibers as well as tyrosine hydroxylase (TH) positive sympathetic fibers, there is a differential organization of sensory vs. sympathetic fibers within the periosteum. In both layers, the great majority of TH+ fibers are closely associated with CD31+ blood vessels and wind around the larger vessels in a corkscrew pattern. In contrast, the majority of CGRP+ and NF200+ sensory fibers in both layers lack a clear association with CD31+ blood vessels and appear to be organized in a dense net-like meshwork to detect mechanical distortion of periosteum and bone. This organization would explain why stabilization/fixation causes a marked attenuation of movement-evoked fracture pain. Understanding the organization, plasticity and molecular characteristics of sensory and sympathetic nerve fibers innervating the skeleton may permit the development of novel mechanism-based therapies for treating non-malignant skeletal pain.

show abstract

Section: Cambium Layermentioning

confidence: 99%

Organization of a unique net-like meshwork of CGRP+ sensory fibers in the mouse periosteum: Implications for the generation and maintenance of bone fracture pain

Martin

Jiménez-Andrade

Ghilardi

et al. 2007

Neuroscience Letters

105

View full text Add to dashboard Cite

show abstract

“…Injury or inflammation results in the release of various chemical mediators (e.g., prostaglandins, cytokines, and growth factors). These chemical mediators stimulate osteoclast activity, activate nociceptors, and decrease their threshold for activation 45,46) . Additionally, transient-receptor potential vanilloid 1 (TRPV1) has also been reported to be upregulated in the dorsal root ganglion (DRG) of OVX rats 39) .…”

Section: The Mechanism Of Osteoporotic Painmentioning

confidence: 99%

Pathomechanisms and management of osteoporotic pain with no traumatic evidence

Orita

Inage

Suzuki

et al. 2017

Spine Surg Relat Res

View full text Add to dashboard Cite

Abstract:Introduction: Osteoporosis is a pathological state with an unbalanced bone metabolism mainly caused by accelerated osteoporotic osteoclast activity due to a postmenopausal estrogen deficiency, and it causes some kinds of pain, which can be divided into two types: traumatic pain due to a fragility fracture from impaired rigidity, and pain derived from an osteoporotic pathology without evidence of fracture. We aimed to review the concepts of osteoporosis-related pain and its management.Methods: We reviewed clinical and basic articles on osteoporosis-related pain, especially with a focus on the mechanism of pain derived from an osteoporotic pathology (i.e., osteoporotic pain) and its pharmacological treatment.Results: Osteoporosis-related pain tends to be robust and acute if it is due to fracture or collapse, whereas pathologyrelated osteoporotic pain is vague and dull. Non-traumatic osteoporotic pain can originate from an undetectable microfracture or structural change such as muscle fatigue in kyphotic patients. Furthermore, basic studies have shown that the osteoporotic state itself is related to pain or hyperalgesia with increased pain-related neuropeptide expression or acid-sensing channels in the local tissue and nervous system. Traditional treatment for osteoporotic pain potentially prevents possible fracture-induced pain by increasing bone mineral density and affecting related mediators such as osteoclasts and osteoblasts. The most common agent for osteoporotic pain management is a bisphosphonate. Other non-osteoporotic analgesic agents such as celecoxib have also been reported to have a suppressive effect on osteoporotic pain.Conclusions: Osteoporotic pain has traumatic and non-traumatic factors. Anti-osteoporotic treatments are effective for osteoporotic pain, as they improve bone structure and the condition of the pain-related sensory nervous system. Physicians should always consider these matters when choosing a treatment strategy that would best benefit patients with osteoporotic pain.

show abstract

“…Microfractures due to mechanical stress are also associated with bone pain, as are changes in intraosseous pressure. 64 Osteoporosis caused by androgen deprivation in patients with advanced prostate cancer may significantly contribute to bone pain and skeletal fracture. 65,66 Bisphosphonates, due to their primary effect on the osteoclast, would not be expected to have an effect on these mechanical causes of bone pain.…”

Section: Bone Painmentioning

confidence: 99%

The potential role of bisphosphonates in prostate cancer

Oades

Coxon

Colston

2002

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Skeletal morbidity secondary to metastases and osteoporosis is common in patients with advanced prostate cancer. Despite the typically sclerotic nature of prostate cancer metastases, osteoclast mediated osteolysis may play a significant role. This review addresses the newly recognised antitumour effects of bisphosphonates in addition to their role in inhibiting osteoclast mediated bone resorption. Both preclinical and clinical evidence of a role for bisphosphonates in the treatment and prevention of bone metastases secondary to prostate cancer is assessed.

show abstract

Pathophysiology of bone pain: A review

Cited by 64 publications

References 76 publications

Organization of a unique net-like meshwork of CGRP+ sensory fibers in the mouse periosteum: Implications for the generation and maintenance of bone fracture pain

Organization of a unique net-like meshwork of CGRP+ sensory fibers in the mouse periosteum: Implications for the generation and maintenance of bone fracture pain

Pathomechanisms and management of osteoporotic pain with no traumatic evidence

The potential role of bisphosphonates in prostate cancer

Contact Info

Product

Resources

About