ReviewBone2020
No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing.
Review in Bone, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06420141 (The Prevalence of Neuropathic Pain Pathophysiology Associated With Ankle Fracture), which is not on this map. Cited by 65 papers.
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.
The Prevalence of Neuropathic Pain Pathophysiology Associated With Ankle Fracture
Who cites it
65 citing papers in PubMed, 98 citations in OpenAlex.
- The miR-212-3p/transferrin axis promotes bone regeneration by modulating iron homeostasis through Schwann cell Exosome-BMSCs communication.Bioactive materials · 2026Article
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio-Interactive Materials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Dual-gene regulation of NGF overexpression and P75NTR knockdown enhances BMSC osteogenesis by suppressing pyroptosis.iScience · 2026Article
- Neuroendocrine and neural control of bone mass in health and disease.The Journal of clinical investigation · 2026Review
- Expression of Calcitonin Gene-related Peptide and Its Application to Cochlear Implantation Under Local Anesthesia With Monitored Anesthesia Care in the Very Elderly: The University of California, Los Angeles, Experience.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2026Article
- Composite hydrogel-microsphere delivery system promotes early nerve-mediated bone regeneration and late-stage mechanotransduction-driven bone remodeling via sequential release of NGF and Yoda1.Bioactive materials · 2026Article
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- Article
- Nociceptor Neurons Facilitate Orthodontic Tooth Movement via Piezo2 in Mice.Journal of dental research · 2025Article
- Structurally and Functionally Adaptive Biomimetic Periosteum: Materials, Fabrication, and Construction Strategies.Exploration (Beijing, China) · 2025Review
- Accelerated Bone Healing via Electrical Stimulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Biomaterial-based strategies for bone cement: modulating the bone microenvironment and promoting regeneration.Journal of nanobiotechnology · 2025Review
- Crafting the future of bone regeneration: the promise of supramolecular peptide nanofiber hydrogels.Frontiers in bioengineering and biotechnology · 2025Review
- The prevalence of neuropathic pain pathophysiology associated with ankle fracture: A study protocol.PloS one · 2025Article
- Impact of Different Cell Types on the Osteogenic Differentiation Process of Mesenchymal Stem Cells.Stem cells international · 2025Review
- A Procedural Overview of the Involvement of Small Molecules in the Nervous System in the Regulation of Bone Healing.International journal of nanomedicine · 2025Review
- Recapitulating the bone extracellular matrix through 3D bioprinting using various crosslinking chemistries.Frontiers in bioengineering and biotechnology · 2025Review
- Article
- Neuronal regulation of bone and tendon injury repair: a focused review.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
5 more citing papers are in PubMed but not listed here.
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
Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their pain-promoting effects. Finally, further examination of protein-sequestering antibodies and/or small molecule agonists and antagonists may lead to new therapies that can decrease the rate of delayed union/nonunion outcomes and fracture-associated pain.
Indexed as
Identifiers
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.