ArticleNeuroscience2014
μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.
Article in Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Peptide-Based Approaches for Pain Relief and Healing in Wounds.International journal of molecular sciences · 2026Review
- The opioid system in depression.Neuroscience and biobehavioral reviews · 2022Review
- Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms-A Scoping Review.Journal of clinical medicine · 2021Article
- Multifunctional Opioid-Derived Hybrids in Neuropathic Pain: Preclinical Evidence, Ideas and Challenges.Molecules (Basel, Switzerland) · 2020Review
- Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.Neuropharmacology · 2019Article
- Intracellular emetic signaling cascades by which the selective neurokinin type 1 receptor (NKNeurochemistry international · 2019Article
- Plasma Concentration of Norepinephrine, β-endorphin, and Substance P in Lame Dairy Cows.Journal of veterinary research · 2018Article
- Nerve Decompression Improves Spinal Synaptic Plasticity of Opioid Receptors for Pain Relief.Neurotoxicity research · 2018Article
- Transmission pathways and mediators as the basis for clinical pharmacology of pain.Expert review of clinical pharmacology · 2016Article
- Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray.Reproductive sciences (Thousand Oaks, Calif.) · 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
- Neurokinin 1 and opioid receptors: relationships and interactions in nervous system.Translational perioperative and pain medicine · 2016Article
- Stress and pain response after oligofructose induced-lameness in dairy heifers.Journal of veterinary science · 2015Article
- Expression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.Neuroscience · 2014Article
- Impact of physical activity on pain perception in an animal model of endometriosis.Journal of endometriosis and pelvic pain disordersArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms.
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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 OpenQuestion graph.