ArticlePain2014
Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain.
Article in Pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions.The journal of pain · 2017Pooled it
- The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain.JCI insight · 2026Article
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- The roles of the nerve-immune axis in modulating bone regeneration.Bone research · 2026Review
- Pain after osteoporotic fractures using mouse models and patient samples.Journal of bone and mineral metabolism · 2026Article
- Experimental Gestational Diabetes Mellitus Prolongs Post-Incisional Mechanical Hypersensitivity and Increases Cutaneous Neuro-Immune Markers in Adult Female Offspring.Journal of pain research · 2026Article
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- Review
- Accelerated fracture healing accompanied with traumatic brain injury: A review of clinical studies, animal models and potential mechanisms.Journal of orthopaedic translation · 2025Review
- Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.Life science alliance · 2024Article
- Article
- Expert opinion on heat therapy for teenagers' musculoskeletal pain management.Annals of translational medicine · 2024Review
- SrHPOMaterials today. Bio · 2024Article
- Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.Current osteoporosis reports · 2024Review
- Role of the Neurologic System in Fracture Healing: An Extensive Review.Current osteoporosis reports · 2024Review
- Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.Current osteoporosis reports · 2024Review
- Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.Bone research · 2023Review
- Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications.Current osteoporosis reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in nonhealed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.