ArticlePain2015
Facilitated spinal neuropeptide signaling and upregulated inflammatory mediator expression contribute to postfracture nociceptive sensitization.
Article in Pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Calcitonin Gene-Related Peptide (CGRP) in Bone Repair and Musculoskeletal Pain: A Scoping Review of Skeletal Regeneration, Joint and Tendon Involvement, and CGRP-Targeted Therapies.Calcified tissue international · 2026Article
- Article
- 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
- The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review.Journal of pain research · 2023Review
- Artesunate Therapy Alleviates Fracture-Associated Chronic Pain After Orthopedic Surgery by Suppressing CCL21-Dependent TREM2/DAP12 Inflammatory Signaling in Mice.Frontiers in pharmacology · 2022Article
- Spinal manifestations of CLN1 disease start during the early postnatal period.Neuropathology and applied neurobiology · 2021Article
- Pathophysiology of musculoskeletal pain: a narrative review.Therapeutic advances in musculoskeletal disease · 2021Review
- Article
- The emergence of animal models of chronic pain and logistical and methodological issues concerning their use.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Article
- Article
- The Rodent Tibia Fracture Model: A Critical Review and Comparison With the Complex Regional Pain Syndrome Literature.The journal of pain · 2018Review
- Exercise Reverses Nociceptive Sensitization, Upregulated Neuropeptide Signaling, Inflammatory Changes, Anxiety, and Memory Impairment in a Mouse Tibia Fracture Model.Anesthesiology · 2018Article
- Complex regional pain syndrome - phenotypic characteristics and potential biomarkers.Nature reviews. Neurology · 2018Review
- Article
- Article
- Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat.Spinal cord · 2016Article
- New Concepts in Complex Regional Pain Syndrome.Hand clinics · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tibia fracture induces exaggerated substance P (SP) and calcitonin gene-related peptide (CGRP) signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hind limbs of rats similar to those seen in complex regional pain syndrome. Inflammatory changes in the spinal cord contribute to nociceptive sensitization in a variety of animal pain models. This study tested the hypothesis that fracture-induced exaggerated neuropeptide signaling upregulates spinal inflammatory mediator expression, leading to postfracture hind limb nociceptive sensitization. At 4 weeks after performing tibia fracture and casting in rats, we measured hind limb allodynia, unweighting, warmth, edema, and spinal cord neuropeptide and inflammatory mediator content. The antinociceptive effects of intrathecally injected neuropeptide and inflammatory mediator receptor antagonists were evaluated in fracture rats. Transgenic fracture mice lacking SP or the CGRP RAMP1 receptor were used to determine the effects of neuropeptide signaling on postfracture pain behavior and spinal inflammatory mediator expression. Hind limb allodynia, unweighting, warmth, edema, increased spinal SP and CGRP, and increased spinal inflammatory mediator expression (TNF, IL-1, IL-6, CCL2, and nerve growth factor) were observed at 4 weeks after fracture in rats. Fracture-induced increases in spinal inflammatory mediators were not observed in fracture mice lacking SP or the CGRP receptor, and these mice had attenuated postfracture nociceptive sensitization. Intrathecal injection of selective receptor antagonists for SP, CGRP, TNF, IL-1, IL-6, CCL2, or nerve growth factor each reduced pain behaviors in the fracture rats. Collectively, these data support the hypothesis that facilitated spinal neuropeptide signaling upregulates the expression of spinal inflammatory mediators contributing to nociceptive sensitization in a rodent fracture model of complex regional pain syndrome.
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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.