ArticleProceedings of the National Academy of Sciences of the United States of America2005
Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: a potential component of nociception.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 75 citations in OpenAlex.
- The Neuroimmune Axis in Gastric Cancer: Bridging Neural Regulation, Tumor Microenvironment, and Immunotherapy.Oncology research · 2026Review
- Article
- Diagnostic and Therapeutic Potential of Substance P/NK1 Receptor in Primary Dysmenorrhea: A Pilot Study.Health science reports · 2026Article
- Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone.Frontiers in pharmacology · 2023Article
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Physiopathological Role of Neuroactive Steroids in the Peripheral Nervous System.International journal of molecular sciences · 2020Review
- Allopregnanolone and Progesterone in Experimental Neuropathic Pain: Former and New Insights with a Translational Perspective.Cellular and molecular neurobiology · 2019Review
- Repurposing steroidogenesis inhibitors for the therapy of neuropsychiatric disorders: Promises and caveats.Neuropharmacology · 2019Review
- Novel Approaches for the Treatment of Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2019Review
- Beneficial effects of Gelsemium-based treatment against paclitaxel-induced painful symptoms.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Article
- Neurosteroids in Pain Management: A New Perspective on an Old Player.Frontiers in pharmacology · 2018Review
- Transcriptomics Analysis of Crassostrea hongkongensis for the Discovery of Reproduction-Related Genes.PloS one · 2015Article
- Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: a crucial benefit from endogenous level analysis.Psychopharmacology · 2014Review
- Frontiers in therapeutic development of allopregnanolone for Alzheimer's disease and other neurological disorders.Frontiers in cellular neuroscience · 2014Review
- Analgesic strategies aimed at stimulating the endogenous production of allopregnanolone.Frontiers in cellular neuroscience · 2014Review
- Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.PloS one · 2013Article
- Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts.Psychopharmacology · 2012Article
- Comparative Analysis of Gelsemine and Gelsemium sempervirens Activity on Neurosteroid Allopregnanolone Formation in the Spinal Cord and Limbic System.Evidence-based complementary and alternative medicine : eCAM · 2011Article
- Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy-induced painful neuropathy.Cellular and molecular life sciences : CMLS · 2010Article
- The progesterone derivative dydrogesterone down-regulates neurokinin 1 receptor expression on lymphocytes, induces a Th2 skew and exerts hypoalgesic effects in mice.Journal of molecular medicine (Berlin, Germany) · 2006Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A crucial biochemical reaction in vertebrates is progesterone conversion into neuroactive metabolites such as dihydroprogesterone (5alpha-DHP) and tetrahydroprogesterone (3alpha,5alpha-THP), which regulate several neurobiological processes, including stress, depression, neuroprotection, and analgesia. 3alpha,5alpha-THP is a potent stimulator of type A receptors of GABA, the main inhibitory neurotransmitter. Here, we show that in the spinal sensory circuit progesterone conversion into 5alpha-DHP and 3alpha,5alpha-THP is inhibited dose-dependently by substance P (SP), a major mediator of painful signals. We developed a triple-labeling approach coupled with multichannel confocal microscope analysis, which revealed that, in the spinal cord (SC), SP-releasing afferents project on sensory neurons expressing simultaneously neurokinin 1 receptors (rNK1) and key enzymes catalyzing progesterone metabolism. Evidence for a potent inhibitory effect of SP on 5alpha-DHP and 3alpha,5alpha-THP formation in the SC was provided by combining pulse-chase experiments using [3H]progesterone as precursor, HPLC, recrystallization of [3H]metabolites to constant specific activity, and continuous flow detection of radioactive steroids. The action of SP on progesterone metabolism was mimicked by the rNK1-specific agonist [Sar-9,Met(O2)11]-SP. The selective rNK1 antagonist SR140333 totally reversed the effect of SP on progesterone conversion into 5alpha-DHP and 3alpha,5alpha-THP. These results provide direct evidence for the occurrence of anatomical and functional interactions between the SP-rNK1 system and neuroactive steroid-producing cells in the SC. The data suggest that, through the local control of 3alpha,5alpha-THP concentration in spinal sensory circuit, the SP-rNK1 system may indirectly interfere with GABA(A) receptor activity in the modulation of nociceptive transmission.
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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.