ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 190 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pain Modulation in RA - Influence of Adalimumab. A Randomized, Placebo-controlled Study Using Functional Magnetic Resonance Imaging (PARADE)
Evaluation of the Effect of Ketamine on Remifentanil-induced Hyperalgesia Using Filaments, an Algometer, and Interleukins: a Double-blind, Randomized Study
Who cites it
190 citing papers in PubMed, 2 syntheses or guidelines pooled it, 427 citations in OpenAlex.
- Effects of Drug Administration on Postoperative Pain in Orthognathic Surgery: A Systematic Review.Clinical and experimental dental research · 2025Pooled it
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.BMC musculoskeletal disorders · 2017Trial
- The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users.Physiology & behavior · 2016Trial
- Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone-maintained patients.Addiction biology · 2008Trial
- Trial
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Molecular Mechanisms Underlying Burn-Injury Induced Pain: From Inflammation to Epigenetics.Military medicine · 2025Review
- Long-Term Clinical and Molecular Changes in Dry Eye Disease and Chronic Ocular Pain.International journal of molecular sciences · 2025Article
- Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery.Journal of clinical medicine · 2025Article
- Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats.Molecular psychiatry · 2025Article
- The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Morphine-Driven m6A Epitranscriptomic Neuroadaptations in Primary Cortical Cultures.Molecular neurobiology · 2024Article
- Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats.bioRxiv : the preprint server for biology · 2024Article
- Promising immunomodulators for management of substance and alcohol use disorders.Expert opinion on pharmacotherapy · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Effect of NLRP3 inflammasome induced astrocyte phenotype alteration in morphine tolerance.Frontiers in pharmacology · 2024Article
- Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.Neurochemical research · 2023Article
- Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics.Pharmaceuticals (Basel, Switzerland) · 2023Review
130 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The present experiments examined the role of spinal proinflammatory cytokines [interleukin-1beta (IL-1)] and chemokines (fractalkine) in acute analgesia and in the development of analgesic tolerance, thermal hyperalgesia, and tactile allodynia in response to chronic intrathecal morphine. Chronic (5 d), but not acute (1 d), intrathecal morphine was associated with a rapid increase in proinflammatory cytokine protein and/or mRNA in dorsal spinal cord and lumbosacral CSF. To determine whether IL-1 release modulates the effects of morphine, intrathecal morphine was coadministered with intrathecal IL-1 receptor antagonist (IL-1ra). This regimen potentiated acute morphine analgesia and inhibited the development of hyperalgesia, allodynia, and analgesic tolerance. Similarly, intrathecal IL-1ra administered after the establishment of morphine tolerance reversed hyperalgesia and prevented the additional development of tolerance and allodynia. Fractalkine also appears to modulate the effects of intrathecal morphine because coadministration of morphine with intrathecal neutralizing antibody against the fractalkine receptor (CX3CR1) potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Fractalkine may be exerting these effects via IL-1 because fractalkine (CX3CL1) induced the release of IL-1 from acutely isolated dorsal spinal cord in vitro. Finally, gene therapy with an adenoviral vector encoding for the release of the anti-inflammatory cytokine IL-10 also potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Taken together, these results suggest that IL-1 and fractalkine are endogenous regulators of morphine analgesia and are involved in the increases in pain sensitivity that occur after chronic opiates.
Indexed as
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What OpenQuestion holds
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.