ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Dorsal horn neurons firing at high frequency, but not primary afferents, release opioid peptides that produce micro-opioid receptor internalization in the rat spinal cord.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Comparison of tonic spinal cord stimulation, high-frequency and burst stimulation in patients with complex regional pain syndrome: a double-blind, randomised placebo controlled trial.BMC musculoskeletal disorders · 2015Trial
- Morphine-sensitive synaptic transmission emerges in embryonic rat microphysiological model of lower afferent nociceptive signaling.Science advances · 2021Article
- Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms-A Scoping Review.Journal of clinical medicine · 2021Article
- Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.Neuropharmacology · 2019Article
- Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.Bioelectronic medicine · 2019Article
- Article
- Sustained Suppression of Hyperalgesia during Latent Sensitization by μ-, δ-, and κ-opioid receptors and α2A Adrenergic Receptors: Role of Constitutive Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 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
- μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.Neuroscience · 2014Article
- Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons.Neuroscience · 2014Article
- Activation of spinal mu- and delta-opioid receptors potently inhibits substance P release induced by peripheral noxious stimuli.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Substance P induces the reversible formation of varicosities in the dendrites of rat brainstem neurons.Brain research · 2011Article
- NMDA receptors in primary afferents require phosphorylation by Src family kinases to induce substance P release in the rat spinal cord.Neuroscience · 2010Article
- Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulation.BMC neuroscience · 2010Article
- Enkephalins, dynorphins, and beta-endorphin in the rat dorsal horn: an immunofluorescence colocalization study.The Journal of comparative neurology · 2009Article
- Substance P release and neurokinin 1 receptor activation in the rat spinal cord increase with the firing frequency of C-fibers.Neuroscience · 2009Article
- Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.Neuroscience · 2009Article
- Effects of veratridine and high potassium on micro-opioid receptor internalization in the rat spinal cord: stimulation of opioid release versus inhibition of internalization.Journal of neuroscience methods · 2008Article
- Inhibition of opioid release in the rat spinal cord by alpha2C adrenergic receptors.Neuropharmacology · 2008Article
- Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce mu-opioid receptor internalization in the presence of peptidase inhibitors.Brain research · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
To determine what neural pathways trigger opioid release in the dorsal horn, we stimulated the dorsal root, the dorsal horn, or the dorsolateral funiculus (DLF) in spinal cord slices while superfusing them with peptidase inhibitors to prevent opioid degradation. Internalization of mu-opioid receptors (MOR) and neurokinin 1 receptors (NK1R) was measured to assess opioid and neurokinin release, respectively. Dorsal root stimulation at low, high, or mixed frequencies produced abundant NK1R internalization but no MOR internalization, indicating that primary afferents do not release opioids. Moreover, capsaicin and NMDA also failed to produce MOR internalization. In contrast, dorsal horn stimulation elicited MOR internalization that increased with the frequency, being negligible at <10 Hz and maximal at 500 Hz. The internalization was abolished by the MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), in the presence of low Ca2+ and by the Na+ channel blocker lidocaine, confirming that it was caused by opioid release and neuronal firing. DLF stimulation in "oblique" slices (encompassing the DLF and the dorsal horn of T11-L4) produced MOR internalization, but only in areas near the stimulation site. Moreover, cutting oblique slices across the dorsal horn (but not across the DLF) eliminated MOR internalization in areas distal to the cut, indicating that it was produced by signals traveling in the dorsal horn and not via the DLF. These findings demonstrate that some dorsal horn neurons release opioids when they fire at high frequencies, perhaps by integrating signals from the rostral ventromedial medulla, primary afferents, and other areas of the spinal cord.
Indexed as
Identifiers
14534251PMC2561240W1530407921What 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.