ArticleAnesthesiology2016
Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.
Article in Anesthesiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04421209 (Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery), which is not on this map. Cited by 22 papers.
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.
Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery
Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
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- A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.Science translational medicine · 2024Article
- Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus.The journal of headache and pain · 2023Article
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.The journal of pain · 2023Article
- Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis.Gastroenterology · 2023Article
- Membrane bound catechol-O-methytransferase is the dominant isoform for dopamine metabolism in PC12 cells and rat brain.European journal of pharmacology · 2021Article
- β2-and β3-Adrenergic Receptors Contribute to Cancer-Evoked Pain in a Mouse Model of OsteosarcomaFrontiers in pharmacology · 2021Article
- Beyond Amitriptyline: A Pediatric and Adolescent Oriented Narrative Review of the Analgesic Properties of Psychotropic Medications for the Treatment of Complex Pain and Headache Disorders.Children (Basel, Switzerland) · 2020Review
- Plasma Concentrations of Select Inflammatory Cytokines Predicts Pain Intensity 48 Hours Post-Shoulder Muscle Injury.The Clinical journal of pain · 2020Article
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- Systems pharmacogenomics - gene, disease, drug and placebo interactions: a case study in COMT.Pharmacogenomics · 2019Article
- Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions.The journal of pain · 2018Article
- Sustained stimulation of βBrain, behavior, and immunity · 2018Article
- Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.Anesthesiology · 2018Review
- Risk factors and prognosis of pain events during mechanical ventilation: a retrospective study.Journal of intensive care · 2017Article
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundPatients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation.
methodsHere, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486.
resultsThe authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity.
conclusionsPeripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.
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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 Socratic graph.