ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Pooled it
- Conditioned pain modulation is associated with common polymorphisms in the serotonin transporter gene.PloS one · 2011Trial
- Gabapentinoids-duloxetine combination therapy for chronic pain: A mechanism oriented rational to bridge theoretical knowledge and real life setting.British journal of clinical pharmacology · 2026Review
- The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain.bioRxiv : the preprint server for biology · 2026Article
- Rostral Ventromedial Medulla (RVM) Projects to the Lateral Hypothalamic Area (LHA) to Drive Aversion and Anxiety.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The Mechanism of Action of Remote Electrical Neuromodulation (REN) in Treating Migraine and Potentially Other Idiopathic Pain Conditions.Current pain and headache reports · 2025Review
- Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists?Medical sciences (Basel, Switzerland) · 2025Review
- Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice.Nature communications · 2025Article
- BDNF Signaling and Pain Modulation.Cells · 2025Review
- Rotating-pulling-poking manipulation effectively alleviates pain symptoms of lateral ankle sprain: an animal experimental study.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Emerging Psychotropic Drug for the Treatment of Trigeminal Pain: Salvinorin A.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.Brain sciences · 2024Review
- Understanding the Biological Relationship between Migraine and Depression.Biomolecules · 2024Review
- Effect of the novel anti-NGF monoclonal antibody DS002 on the metabolomics of pain mediators, cartilage and bone.Frontiers in pharmacology · 2024Article
- Article
- Gut-Brain Crosstalk and the Central Mechanisms of Orofacial Pain.Brain sciences · 2023Review
- Cell type-specific dissection of sensory pathways involved in descending modulation.Trends in neurosciences · 2023Review
- Descending serotonergic modulation from rostral ventromedial medulla to spinal trigeminal nucleus is involved in experimental occlusal interference-induced chronic orofacial hyperalgesia.The journal of headache and pain · 2023Article
- Article
- Bulbospinal nociceptive ON and OFF cells related neural circuits and transmitters.Frontiers in pharmacology · 2023Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Recent studies indicate that persistent pain after tissue or nerve injury is accompanied by an enhanced net descending facilitatory drive that contributes to an amplification and spread of pain. Although 5-HT-containing neurons in the rostral ventromedial medulla (RVM) provide the major descending serotonergic projection to the spinal cord, it is not clear whether the neurotransmitter 5-HT itself released from RVM-spinal neurons contributes to descending pain modulation. In the present study, we determined the role of the descending 5-HT in rat nocifensive behaviors after persistent pain by selectively depleting functional phenotypes of 5-HT in RVM neurons with regional shRNA interference (RNAi) of tryptophan hydroxylase-2 (Tph-2), the rate-limiting enzyme in the synthesis of neuronal 5-HT. Compared to negative control shRNA, Tph-2 shRNA induced significantly prolonged downregulation of Tph-2 in the RVM and 5-HT in spinal dorsal horn. The 5-HT-depleted rats showed normal pain sensitivity in responses to acute noxious stimulation. However, the same RNAi treatment attenuated formalin-induced spontaneous nocifensive responses and tissue or nerve injury-induced allodynia and hyperalgesia. Furthermore, in control shRNA-treated animals, intra-RVM microinjection of brain-derived neurotrophic factor produced a reversible hyperalgesia, which was completely prevented by Tph-2 RNAi pretreatment. Descending inhibition induced by intra-RVM electrical stimulation, but not microinjection of the mu- or kappa-opioid receptor agonists in control shRNA-treated animals was eliminated in 5-HT-depleted rats. These results indicate that the descending 5-HT from the RVM is an important contributor to pain facilitation during the development of persistent pain, and may not mediate opioid-induced descending inhibition in acute pain.
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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.