ArticleMolecular pain2012
Neuropeptide deficient mice have attenuated nociceptive, vascular, and inflammatory changes in a tibia fracture model of complex regional pain syndrome.
Article in Molecular pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- Preventive Effects of Avocado/Soybean Unsaponifiables on Complex Regional Pain Syndrome Type I in a Rat Model.Biomedicines · 2026Article
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- The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial.Brain sciences · 2025Article
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- Identification of two biological subgroups of complex regional pain syndrome type 1 by transcriptomic profiling of skin and blood in women.Molecular medicine (Cambridge, Mass.) · 2025Article
- Pain persists in mice lacking both Substance P and CGRPα signaling.bioRxiv : the preprint server for biology · 2024Article
- Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes.Pain reports · 2024Article
- Bone Turnover Markers and Wnt Signaling Modulators in Early Complex Regional Pain Syndrome. A Pre-specified Observational Study.Calcified tissue international · 2024Observational
- The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review.Journal of pain research · 2023Review
- Peripheral nerves in the tibial subchondral bone : the role of pain and homeostasis in osteoarthritis.Bone & joint research · 2022Article
- Autonomic Regulation of Nociceptive and Immunologic Changes in a Mouse Model of Complex Regional Pain Syndrome.The journal of pain · 2022Article
- Nerves within bone and their application in tissue engineering of bone regeneration.Frontiers in neurology · 2022Review
- Emerging roles of keratinocytes in nociceptive transduction and regulation.Frontiers in molecular neuroscience · 2022Review
- Complex regional pain syndrome - Autoimmune or functional neurologic syndrome.Journal of translational autoimmunity · 2021Review
- Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Animal Models of Complex Regional Pain Syndrome Type I.Journal of pain research · 2021Review
- Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.International journal of molecular sciences · 2020Observational
- N-methyl-d-aspartate receptor subunit 2B on keratinocyte mediates peripheral and central sensitization in chronic post-ischemic pain in male rats.Brain, behavior, and immunity · 2020Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDistal limb fracture in man can induce a complex regional pain syndrome (CRPS) with pain, warmth, edema, and cutaneous inflammation. In the present study substance P (SP, Tac1(-/-)) and CGRP receptor (RAMP1(-/-)) deficient mice were used to investigate the contribution of neuropeptide signaling to CRPS-like changes in a tibia fracture mouse model. Wildtype, Tac1(-/-), and RAMP1(-/-) mice underwent tibia fracture and casting for 3 weeks, then the cast was removed and hindpaw mechanical allodynia, unweighting, warmth, and edema were tested over time. Hindpaw skin was collected at 3 weeks post-fracture for immunoassay and femurs were collected for micro-CT analysis.
resultsWildtype mice developed hindpaw allodynia, unweighting, warmth, and edema at 3 weeks post-fracture, but in the Tac1(-/-) fracture mice allodynia and unweighting were attenuated and there was no warmth and edema. RAMP1(-/-) fracture mice had a similar presentation, except there was no reduction in hindpaw edema. Hindpaw skin TNFα, IL-1β, IL-6 and NGF levels were up-regulated in wildtype fracture mice at 3 weeks post-fracture, but in the Tac1(-/-) and RAMP1(-/-) fracture mice only IL-6 was increased. The epidermal keratinocytes were the cellular source for these inflammatory mediators. An IL-6 receptor antagonist partially reversed post-fracture pain behaviors in wildtype mice.
conclusionsIn conclusion, both SP and CGRP are critical neuropeptide mediators for the pain behaviors, vascular abnormalities, and up-regulated innate immune responses observed in the fracture hindlimb. We postulate that the residual pain behaviors observed in the Tac1(-/-) and RAMP1(-/-) fracture mice are attributable to the increased IL-6 levels observed in the hindpaw skin after fracture.
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