ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Inhibition by spinal mu- and delta-opioid agonists of afferent-evoked substance P release.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 117 citations in OpenAlex.
- Peptide-Based Approaches for Pain Relief and Healing in Wounds.International journal of molecular sciences · 2026Review
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- Anatomical Analysis of Transient Potential Vanilloid Receptor 1 (Frontiers in molecular neuroscience · 2022Article
- Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels.Cellular and molecular neurobiology · 2021Review
- cAMP signaling through protein kinase A and Epac2 induces substance P release in the rat spinal cord.Neuropharmacology · 2021Article
- Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue.International journal of molecular sciences · 2020Article
- Neurokinin 1 receptor activation in the rat spinal cord maintains latent sensitization, a model of inflammatory and neuropathic chronic pain.Neuropharmacology · 2020Article
- Lipid rafts in glial cells: role in neuroinflammation and pain processing.Journal of lipid research · 2020Review
- Opioid Receptors in Immune and Glial Cells-Implications for Pain Control.Frontiers in immunology · 2020Review
- Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.Neuropharmacology · 2019Article
- Characterization of Analgesic Actions of the Chronic Intrathecal Infusion of H-Dmt-D-Arg-Phe-Lys-NH2 in Rat.Neuromodulation : journal of the International Neuromodulation Society · 2019Article
- Article
- Mechanisms of μ-opioid receptor inhibition of NMDA receptor-induced substance P release in the rat spinal cord.Neuropharmacology · 2018Article
- Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model.The Korean journal of pain · 2018Article
- Age Differences in the Time Course and Magnitude of Changes in Circulating Neuropeptides After Pain Evocation in Humans.The journal of pain · 2017Article
- Current and Future Issues in the Development of Spinal Agents for the Management of Pain.Current neuropharmacology · 2017Review
- Neurokinin 1 and opioid receptors: relationships and interactions in nervous system.Translational perioperative and pain medicine · 2016Article
- Endomorphin-2 Inhibition of Substance P Signaling within Lamina I of the Spinal Cord Is Impaired in Diabetic Neuropathic Pain Rats.Frontiers in molecular neuroscience · 2016Article
- Discovery of Novel Multifunctional Ligands with μ/δ Opioid Agonist/Neurokinin-1 (NK1) Antagonist Activities for the Treatment of Pain.Journal of medicinal chemistry · 2015Article
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.Pharmacological reviews · 2015Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Opioid mu- and delta-receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and in vivo. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the mu agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) (1 microM) and decreased by the delta agonist [D-Phe2,5]-enkephalin (DPDPE) (1 microM). In vivo, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the kappa agonist trans-(1S,2S)-3,4-dichloro-N-mathyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the mu and delta agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.
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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.