ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Primary afferent NMDA receptors increase dorsal horn excitation and mediate opiate tolerance in neonatal rats.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
44 citing papers in PubMed, 69 citations in OpenAlex.
- Sensory neuron BRAF mediates opioid-induced hyperalgesia and tolerance via presynaptic NMDA receptor hyperactivity.The Journal of clinical investigation · 2026Article
- GαScience signaling · 2025Article
- Targeting Excitatory Glutamate Receptors for Morphine Tolerance: A Narrative Review.CNS neuroscience & therapeutics · 2025Review
- Article
- Tiam1 is part of a novel mechanism for morphine tolerance and hyperalgesia.Brain : a journal of neurology · 2024Article
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.Brain : a journal of neurology · 2024Article
- Opioid-Induced Hyperalgesia and Tolerance Are Driven by HCN Ion Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.Nature communications · 2022Article
- Advances and Barriers in Understanding PresynapticFrontiers in molecular neuroscience · 2022Review
- Article
- Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain.Cellular and molecular life sciences : CMLS · 2019Review
- α2δ-1-Bound N-Methyl-D-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents.Anesthesiology · 2019Article
- Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior.Neuron · 2019Article
- μ-Opioid receptors in primary sensory neurons are essential for opioid analgesic effect on acute and inflammatory pain and opioid-induced hyperalgesia.The Journal of physiology · 2019Article
- Increased α2δ-1-NMDA receptor coupling potentiates glutamatergic input to spinal dorsal horn neurons in chemotherapy-induced neuropathic pain.Journal of neurochemistry · 2019Article
- Mitogen-activated protein kinase signaling mediates opioid-induced presynaptic NMDA receptor activation and analgesic tolerance.Journal of neurochemistry · 2019Article
- Mechanisms of μ-opioid receptor inhibition of NMDA receptor-induced substance P release in the rat spinal cord.Neuropharmacology · 2018Article
- AMPKα1 knockout enhances nociceptive behaviors and spinal glutamatergic synaptic activities via production of reactive oxygen species in the spinal dorsal horn.Neuroscience · 2016Article
- BK channels in microglia are required for morphine-induced hyperalgesia.Nature communications · 2016Article
- Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats.British journal of pharmacology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Repeated exposure to opiates produces analgesic tolerance, which limits their clinical usefulness. Whole-cell voltage-clamped lamina I cells in spinal slices from opiate-tolerant neonatal rats show an increase in miniature, spontaneous, and primary afferent-evoked EPSCs when compared with lamina I cells from opiate-naive rat spinal slices. This increased excitation can be blocked by the NMDA receptor (NMDAR) antagonist APV, apparently acting at NMDARs on primary afferents. Consistent with these results, electron microscopy demonstrates an increased incidence of NMDARs in substance P-containing spinal dorsal horn primary afferent terminals in opiate-tolerant rats. Moreover, superfusion of spinal slices from opiate-tolerant rats with NMDA produces a reversible increase in miniature EPSC (mEPSC) frequency in contrast to a decrease in mEPSC frequency produced by NMDA in opiate-naive slices. Finally, NMDAR antagonists inhibit the expression of opiate tolerance both in inhibiting EPSCs in spinal slices and in inhibiting behavioral nociceptive responses to heat. NMDAR antagonists have been reported in many studies to inhibit morphine analgesic tolerance. Our studies suggest that an increase in primary afferent NMDAR expression and activity mediates a hypersensitivity to noxious stimuli and causes the inhibition of opiate efficacy, which defines tolerance.
Indexed as
Identifiers
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.