ArticlePain2012
Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors.
Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 59 citations in OpenAlex.
- Targeting Excitatory Glutamate Receptors for Morphine Tolerance: A Narrative Review.CNS neuroscience & therapeutics · 2025Review
- Preclinical Insights into the Role of Kir4.1 in Chronic Pain and Depression: Mechanisms and Therapeutic Potential.Biomolecules · 2025Review
- Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.The international journal of neuropsychopharmacology · 2023Article
- Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar-Kyoto rats.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions.Brain sciences · 2022Article
- Transcutaneous auricular vagal nerve stimulation releases extrapineal melatonin and reduces thermal hypersensitivity in Zucker diabetic fatty rats.Frontiers in neuroscience · 2022Article
- NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain.Frontiers in cellular neuroscience · 2022Review
- Ameliorating Effect on Aβ-Induced Alzheimer's Mice byMolecules (Basel, Switzerland) · 2021Article
- Is there a role for melatonin in the ICU?The Southern African journal of critical care : the official journal of the Critical Care Society · 2021Review
- Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice.International journal of molecular sciences · 2020Article
- A Fatal Alliance between Microglia, Inflammasomes, and Central Pain.International journal of molecular sciences · 2020Review
- Role of Melatonin in the Regulation of Pain.Journal of pain research · 2020Review
- Transcutaneous Auricular Vagus Nerve Stimulation at 20 Hz Improves Depression-Like Behaviors and Down-Regulates the Hyperactivity of HPA Axis in Chronic Unpredictable Mild Stress Model Rats.Frontiers in neuroscience · 2020Article
- Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care.Cell death & disease · 2019Review
- Distribution and colocalization of melatonin 1a-receptor and NADPH-d in the trigeminal system of rat.PeerJ · 2019Article
- Brain injury results in lower levels of melatonin receptors subtypes MT1 and MT2.Neuroscience letters · 2017Article
- Melatonin prevents morphine-induced hyperalgesia and tolerance in rats: role of protein kinase C and N-methyl-D-aspartate receptors.BMC anesthesiology · 2015Article
- Pain and depression comorbidity: a preclinical perspective.Behavioural brain research · 2015Review
- Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain.Psychopharmacology · 2014Article
- An altered spinal serotonergic system contributes to increased thermal nociception in an animal model of depression.Experimental brain research · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. As compared with Wistar rats, WKY rats showed a lower plasma melatonin level, downregulation of the melatonin MT1 receptor, but upregulation of the NR1 subunit of the NMDA receptor in the ipsilateral trigeminal subnucleus caudalis (Sp5C). Intracisternal administration of 6-chloromelatonin (250 μg, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
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.