ArticleBrain, behavior, and immunity2012
Prior exposure to repeated morphine potentiates mechanical allodynia induced by peripheral inflammation and neuropathy.
Article in Brain, behavior, and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 52 citations in OpenAlex.
- Morphine aggravates inflammatory, behavioral, and hippocampal structural deficits in septic rats.Scientific reports · 2023Article
- Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease.Neural plasticity · 2023Review
- Repeated blast mild traumatic brain injury and oxycodone self-administration produce interactive effects on neuroimaging outcomes.Addiction biology · 2022Article
- Enhanced H3K4 Trimethylation in TNF-Mediators of inflammation · 2021Article
- Sex differences in neuro(auto)immunity and chronic sciatic nerve pain.Biology of sex differences · 2020Review
- Article
- Morphine immunomodulation prolongs inflammatory and postoperative pain while the novel analgesic ZH853 accelerates recovery and protects against latent sensitization.Journal of neuroinflammation · 2019Article
- Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice.Anesthesiology · 2019Article
- Repeated Morphine Prolongs Postoperative Pain in Male Rats.Anesthesia and analgesia · 2019Article
- MicroRNA-124 and microRNA-146a both attenuate persistent neuropathic pain induced by morphine in male rats.Brain research · 2018Article
- Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats.Brain, behavior, and immunity · 2018Article
- Astrocytic hypertrophy in the rat ventral tegmental area following chronic morphine differs with age.Journal of neurology and neurorehabilitation research · 2018Article
- Glial and neuroinflammatory targets for treating substance use disorders.Drug and alcohol dependence · 2017Review
- Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners.Neural plasticity · 2017Article
- Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury.Brain, behavior, and immunity · 2016Article
- The dark side of opioids in pain management: basic science explains clinical observation.Pain reports · 2016Article
- Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Review
- Activation of CXCL10/CXCR3 signaling attenuates morphine analgesia: involvement of Gi protein.Journal of molecular neuroscience : MN · 2014Article
- Pathological pain and the neuroimmune interface.Nature reviews. Immunology · 2014Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Opioids, such as morphine, induce potent analgesia and are the gold standard for the treatment of acute pain. However, opioids also activate glia, inducing pro-inflammatory cytokine and chemokine production, which counter-regulates the analgesic properties of classical opioid receptor activation. It is not known how long these adverse pro-inflammatory effects last or whether prior morphine could sensitize the central nervous system (CNS) such that responses to a subsequent injury/inflammation would be exacerbated. Here, multiple models of inflammation or injury were induced two days after morphine (5mg/kg b.i.d., five days , s.c.) to test the generality of morphine sensitization of later pain. Prior repeated morphine potentiated the duration of allodynia from peripheral inflammatory challenges (complete Freund's adjuvant (CFA) into either hind paw skin or masseter muscle) and from peripheral neuropathy (mild chronic constriction injury (CCI) of the sciatic nerve). Spinal cord and trigeminal nucleus caudalis mRNAs were analyzed to identify whether repeated morphine was sufficient to alter CNS expression of pro-inflammatory response genes, measured two days after cessation of treatment. Prior morphine elevated IL-1β mRNA at both sites, MHC-II and TLR4 in the trigeminal nucleus caudalis but not spinal cord, but not glial activation markers at either site. Finally, in order to identify whether morphine sensitized pro-inflammatory cytokine release, spinal cord was isolated two days after morphine dosing for five days , and slices stimulated ex vivo with lipopolysaccharide. The morphine significantly induced TNFα protein release. Therefore, repeated morphine is able to sensitize subsequent CNS responses to immune challenges.
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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.