ArticleEuropean journal of pain (London, England)2009
Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome.
Article in European journal of pain (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 65 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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- Brief research report: Repurposing pentoxifylline to treat intense acute swimming-Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms.Frontiers in pharmacology · 2022Article
- Emerging roles of keratinocytes in nociceptive transduction and regulation.Frontiers in molecular neuroscience · 2022Review
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- Bee venom reduces burn-induced pain via the suppression of peripheral and central substance P expression in mice.Journal of veterinary science · 2021Article
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- Effects of pentoxifylline and alendronate on fracture healing in ovariectomy-induced osteoporosis in rats.Veterinary research forum : an international quarterly journal · 2019Article
- The Rodent Tibia Fracture Model: A Critical Review and Comparison With the Complex Regional Pain Syndrome Literature.The journal of pain · 2018Review
- Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome.The journal of pain · 2018Article
- Article
- The effects of pentoxifylline adminstration on fracture healing in a postmenopausal osteoporotic rat model.Laboratory animal research · 2017Article
- Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.Anesthesia and analgesia · 2016Article
- Mast Cell-Mediated Mechanisms of Nociception.International journal of molecular sciences · 2015Review
- Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture.Neuroscience · 2015Article
- Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice.Anesthesiology · 2015Article
- Effect of Pentoxifylline Administration on an Experimental Rat Model of Femur Fracture Healing With Intramedullary Fixation.Iranian Red Crescent medical journal · 2015Article
- Article
- Sex differences in a Murine Model of Complex Regional Pain Syndrome.Neurobiology of learning and memory · 2015Article
- Immobilization contributes to exaggerated neuropeptide signaling, inflammatory changes, and nociceptive sensitization after fracture in rats.The journal of pain · 2014Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTibia fracture in rats evokes chronic hindpaw warmth, edema, allodynia, and regional osteopenia, a syndrome resembling complex regional pain syndrome (CRPS). Previous studies suggest that the pathogenesis of some of these changes involves an exaggerated regional inflammatory response to injury and we postulated that inflammatory cytokines contribute to the development of CRPS-like changes after fracture.
methodsThe distal tibia was fractured and the hindlimb casted for 4 weeks. The rats were given drinking water with or without the cytokine inhibitor pentoxifylline (PTX) starting the day before fracture and continuing for 4 weeks, after which time the cast was removed and multiple assays were performed in the hindpaw. PCR and immunoassays were used to evaluate changes in cytokine expression. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and bone microarchitecture was measured by microcomputed tomography (microCT).
resultsTibia fracture chronically up-regulated TNFalpha, IL-1beta and IL-6 mRNA and protein levels in hindpaw skin and PTX treatment significantly reduced the mRNA expression and cytokine protein levels for all these cytokines. PTX inhibited the nociceptive sensitization and some vascular changes, but had insignificant effects on most of the bone-related parameters measured in these studies. Immunostaining of hindpaw skin was negative for immunocyte infiltration at 4 weeks post-fracture.
conclusionsThese results suggest that pro-inflammatory cytokines contribute to the nociceptive and vascular sequelae of fracture and that PTX treatment can reverse these CRPS-like changes.
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