ArticleAnesthesiology2019
Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice.
Article in Anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 26 citations in OpenAlex.
- Variations in Prehospital Analgesic Use Based on Pain Etiology.Biomedicines · 2025Article
- The nonopioid cholinergic agonist GTS-21 mitigates morphine-induced aggravation of burn injury pain together with inhibition of spinal microglia activation in young rats.British journal of anaesthesia · 2022Article
- Fentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- What Did We Learn About Fracture Pain from Animal Models?Journal of pain research · 2022Review
- Fracture-induced pain-like behaviours in a femoral fracture mouse model.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Article
- Distinct non-inflammatory signature of microglia in post-mortem brain tissue of patients with major depressive disorder.Molecular psychiatry · 2021Article
- Modulatory Potential of Cannabidiol on the Opioid-Induced Inflammatory Response.Cannabis and cannabinoid research · 2021Review
- Sex differences in neuro(auto)immunity and chronic sciatic nerve pain.Biology of sex differences · 2020Review
- Assessment, Quantification, and Management of Fracture Pain: from Animals to the Clinic.Current osteoporosis reports · 2020Review
- Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEmerging evidence suggests that opioid use immediately after surgery and trauma may worsen outcomes. In these studies, the authors aimed to determine whether morphine administered for a clinically relevant time period (7 days) in a tibia fracture orthopedic surgery model had adverse effects on postoperative recovery.
methodsMice were given morphine twice daily for 7 days after unilateral tibial fracture and intramedullary pin fixation to model orthopedic surgery and limb trauma. Mechanical allodynia, limb-specific weight bearing, gait changes, memory, and anxiety were measured after injury. In addition, spinal cord gene expression changes as well as glial activation were measured. Finally, the authors assessed the effects of a selective Toll-like receptor 4 antagonist, TAK-242, on nociceptive and functional changes after injury.
resultsTibial fracture caused several weeks of mechanical nociceptive sensitization (F(1, 216) = 573.38, P < 0.001, fracture + vehicle vs. sham + vehicle, n = 10 per group), and this change was exacerbated by the perioperative administration of morphine (F(1, 216) = 71.61, P < 0.001, fracture + morphine vs. fracture + vehicle, n = 10 per group). In additional testing, injured limb weight bearing, gait, and object location memory were worse in morphine-treated fracture mice than in untreated fracture mice. Postfracture expression levels of several genes previously associated with opioid-induced hyperalgesia, including brain-derived neurotrophic factor and prodynorphin, were unchanged, but neuroinflammation involving Toll-like receptor 4 receptor-expressing microglia was observed (6.8 ± 1.5 [mean ± SD] cells per high-power field for fracture + vehicle vs. 12 ± 2.8 fracture + morphine, P < 0.001, n = 8 per /group). Treatment with a Toll-like receptor 4 antagonist TAK242 improved nociceptive sensitization for about 2 weeks in morphine-treated fracture mice (F(1, 198) = 73.36, P < 0.001, fracture + morphine + TAK242 vs. fracture + morphine, n = 10 per group).
conclusionsMorphine treatment beginning at the time of injury impairs nociceptive recovery and other outcomes. Measures preventing glial activation through Toll-like receptor 4 signaling may reduce the adverse consequences of postoperative opioid administration.
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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.