ArticleAnesthesia and analgesia2019
Repeated Morphine Prolongs Postoperative Pain in Male Rats.
Article in Anesthesia and analgesia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Drug tapering in animal research: current practices and challenges.Frontiers in pharmacology · 2025Pooled it
- Effects of putative chronic pain models on locomotor activity in female and male mice.The journal of pain · 2026Article
- Selective TLR4 Antagonism Prevents and Reverses Morphine-Induced Persistent Postoperative Cognitive Dysfunction, Dysregulation of Synaptic Elements, and Impaired BDNF Signaling in Aged Male Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Subfascial infiltration of 0.5% ropivacaine, but not 0.25% ropivacaine, exacerbates damage and inflammation in surgically incised abdominal muscles of rats.Scientific reports · 2022Article
- Article
- The Involvement of Caspases in Neuroinflammation and Neuronal Apoptosis in Chronic Pain and Potential Therapeutic Targets.Frontiers in pharmacology · 2022Review
- Impact of Opioid-Minimizing Pain Protocols After Burn Injury.Journal of burn care & research : official publication of the American Burn Association · 2021Article
- NLRP3 inflammasomes are involved in the progression of postoperative cognitive dysfunction: from mechanism to treatment.Neurosurgical review · 2021Review
- Postoperative cognitive dysfunction is made persistent with morphine treatment in aged rats.Neurobiology of aging · 2021Article
- Sex differences in neuro(auto)immunity and chronic sciatic nerve pain.Biology of sex differences · 2020Review
- An evolutionary medicine perspective on pain and its disorders.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Article
- Morphine immunomodulation prolongs inflammatory and postoperative pain while the novel analgesic ZH853 accelerates recovery and protects against latent sensitization.Journal of neuroinflammation · 2019Article
- Revisiting Tramadol: A Multi-Modal Agent for Pain Management.CNS drugs · 2019Review
- MicroRNA-124 and microRNA-146a both attenuate persistent neuropathic pain induced by morphine in male rats.Brain research · 2018Article
- Improvement ofInternational journal of applied & basic medical researchArticle
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOpioids are effective postoperative analgesics. Disturbingly, we have previously reported that opioids such as morphine can worsen inflammatory pain and peripheral and central neuropathic pain. These deleterious effects are mediated by immune mediators that promote neuronal hyperexcitability in the spinal dorsal horn. Herein, we tested whether perioperative morphine could similarly prolong postoperative pain in male rats.
methodsRats were treated with morphine for 7 days, beginning immediately after laparotomy, while the morphine was tapered in a second group. Expression of genes for inflammatory mediators was quantified in the spinal dorsal horn. In the final experiment, morphine was administered before laparotomy for 7 days.
resultsWe found that morphine treatment after laparotomy extended postoperative pain by more than 3 weeks (time × treatment: P < .001; time: P < .001; treatment: P < .05). Extension of postoperative pain was not related to morphine withdrawal, as it was not prevented by dose tapering (time × treatment: P = .8; time: P < .001; treatment: P = .9). Prolonged postsurgical pain was associated with increased expression of inflammatory genes, including those encoding Toll-like receptor 4, NOD like receptor protein 3 (NLRP3), nuclear factor kappa B (NFκB), caspase-1, interleukin-1β, and tumor necrosis factor (P < .05). Finally, we showed that of preoperative morphine, concluding immediately before laparotomy, similarly prolonged postoperative pain (time × treatment: P < .001; time: P < .001; treatment: P < .001). There is a critical window for morphine potentiation of pain, as a 7-day course of morphine that concluded 1 week before laparotomy did not prolong postsurgical pain.
conclusionsThese studies indicate the morphine can have a deleterious effect on postoperative pain. These studies further suggest that longitudinal studies could be performed to test whether opioids similarly prolong postoperative pain in the clinic.
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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.