Mechanisms of bone pain: Progress in research from bench to bedside

Zhen, Gehua; Fu, Yuhan; Zhang, Chi; Ford, Neil C.; Wu, Xiaojun; Wu, Qichao; Yan, Dong; Chen, Xueming; Cao, Xu; Guan, Yun

doi:10.1038/s41413-022-00217-w

Cited by 30 publications

(18 citation statements)

References 212 publications

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“…Furthermore, more than one structure may be contributing to the pain at any one time. During healing, neovascularisation occurs and minute sensory nerves can penetrate the disrupted annulus and nucleus pulposus, leading to mechanical and chemical sensitization 41 .…”

Section: Discussionmentioning

confidence: 99%

Senescence of endplate osteoclasts induces sensory innervation and spinal pain

Pan,

Benkato,

Han

et al. 2023

Preprint

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Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that greater numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation and H-type vessel growth in the endplate. We also show that there is greater SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

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Section: Discussionmentioning

confidence: 99%

Senescence of endplate osteoclasts induces sensory innervation and spinal pain

Pan,

Benkato,

Han

et al. 2023

Preprint

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“…Local radiotherapy, a commonly used modality has a reported pain response rate of 61% with a median response time of 4 weeks [30]. Whilst there has been increased interest in the study of bone pain [31], a translational paradigm has not successfully allowed the pathophysiology and mechanism of CIBP to inform the choice of pharmacotherapeutics [32]. Opioids remain the mainstay treatment with no evidence to guide the choice of the opioid molecule [3].…”

Section: Discussionmentioning

confidence: 99%

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: a descriptive cohort study

Sulistio

Ling

Finkelstein

et al. 2023

Support Care Cancer

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Purpose We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity, and opioid consumption. Methods We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior, and cognition. Results Among 147 eligible patients, 95.2% completed the assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and was associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with a significantly higher average pain score (4, p=0.009) and a slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). Conclusion There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. Trial registration Retrospectively registered in ANZCTR ACTRN12622000853741 (16/06/2022)

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Section: Discussionmentioning

confidence: 99%

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study

Sulistio

Ling

Finkelstein

et al. 2022

Preprint

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Purpose: We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity and opioid consumption. Methods: We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior and cognition. Results: Among 147 eligible patients, 95.2% completed assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with significantly higher average pain score (4, p=0.009) and slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). Conclusion: There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. Trial registration in ANZCTR ACTRN12622000853741 (16/06/2022) retrospectively registered.

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Mechanisms of bone pain: Progress in research from bench to bedside

Cited by 30 publications

References 212 publications

Senescence of endplate osteoclasts induces sensory innervation and spinal pain

Senescence of endplate osteoclasts induces sensory innervation and spinal pain

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: a descriptive cohort study

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study

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