ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Neural correlates of an injury-free model of central sensitization induced by opioid withdrawal in humans.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging: Implications for Analgesic Drug Development.Anesthesiology · 2016Trial
- The effect of repeated intramuscular alfentanil injections on experimental pain and abuse liability indices in healthy males.The Clinical journal of pain · 2014Trial
- Pain facilitation brain regions activated by nalbuphine are revealed by pharmacological fMRI.PloS one · 2013Trial
- Trial
- Neural correlates underlying high-frequency stimulation-induced secondary hyperalgesia in humans.Pain reports · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.British journal of pharmacology · 2020Article
- Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.Molecular neurobiology · 2019Article
- Response to "Treating patients rather than their functional neuroimages" (Br J Anaesth 2018; 121: 969-71).British journal of anaesthesia · 2019Article
- Resting Functional Connectivity of the Periaqueductal Gray Is Associated With Normal Inhibition and Pathological Facilitation in Conditioned Pain Modulation.The journal of pain · 2018Article
- Altered Signaling in the Descending Pain-modulatory System after Short-Term Infusion of the μ-Opioid Agonist Remifentanil.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Rationale for and approach to preoperative opioid weaning: a preoperative optimization protocol.Perioperative medicine (London, England) · 2017Review
- Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain.Neuropharmacology · 2014Review
- Imaging pain: a potent means for investigating pain mechanisms in patients.British journal of anaesthesia · 2013Review
- Pain, decisions, and actions: a motivational perspective.Frontiers in neuroscience · 2013Article
- Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist.Journal of neuroimmunology · 2012Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Preclinical evidence suggests that opioid withdrawal induces central sensitization (CS) that is maintained by supraspinal contributions from the descending pain modulatory system (DPMS). Here, in healthy human subjects we use functional magnetic resonance imaging to study the supraspinal activity during the withdrawal period of the opioid remifentanil. We used a crossover design and thermal stimuli on uninjured skin to demonstrate opioid withdrawal-induced hyperalgesia (OIH) without a CS-inducing peripheral stimulus. Saline was used in the control arm to account for effects of time. OIH in this injury-free model was observed in a subset of the healthy subjects (responders). Only in these subjects did opioid infusion and withdrawal induce a rise in activity in the mesencephalic-pontine reticular formation (MPRF), an area of the DPMS that has been previously shown to be involved in states of CS in humans, which became significant during the withdrawal phase compared with nonresponders. Paradoxically, this opioid withdrawal-induced rise in MPRF activity shows a significant negative correlation with the behavioral OIH score indicating a predominant inhibitory role of the MPRF in the responders. These data illustrate that in susceptible individuals central mechanisms appear to regulate the expression of OIH in humans in the absence of tissue injury, which might have relevance for functional pain syndromes where a peripheral origin for the pain is difficult to identify.
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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.