ArticleBrain : a journal of neurology2023
A critical brainstem relay for mediation of diffuse noxious inhibitory controls.
Article in Brain : a journal of neurology, 2023. 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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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Perioperative pregabalin does not alter behavioural or diffuse noxious inhibitory control responses in 2 rat models of chronic pain.Pain reports · 2026Article
- Mapping the functional connectome between grey matter and white matter.Communications biology · 2026Article
- Article
- Cellular and molecular basis of neuropathic pain.RMD open · 2026Review
- Virtual reality enhances affective valence and attentional dissociation during exercise but not exercise-induced hypoalgesia.Virtual reality · 2026Article
- Guanfacine as a potential preventive therapy for chronic migraine: a mechanistic hypothesis.Frontiers in neurology · 2026Article
- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Exploring the Spectrum of Temporal Summation and Conditioned Pain Modulation Responses in Pain-Free Individuals Using a Tonic Heat Pain and Cold Pressor Test Paradigms.European journal of pain (London, England) · 2025Observational
- A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.European journal of pain (London, England) · 2025Article
- Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.International journal of molecular sciences · 2025Review
- Multiple Posterior Insula Projections to the Brainstem Descending Pain Modulatory System.International journal of molecular sciences · 2024Article
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.Science advances · 2024Article
- Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.Anesthesiology · 2024Article
- Neuroanatomy of the nociceptive system: From nociceptors to brain networks.International review of neurobiology · 2024Review
- The psychophysiology of music-based interventions and the experience of pain.Frontiers in psychology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The CNS houses naturally occurring pathways that project from the brain to modulate spinal neuronal activity. The noradrenergic locus coeruleus (the A6 nucleus) originates such a descending control whose influence on pain modulation encompasses an interaction with a spinally projecting non-cerulean noradrenergic cell group. Hypothesizing the origin of an endogenous pain inhibitory pathway, our aim was to identify this cell group. A5 and A7 noradrenergic nuclei also spinally project. We probed their activity using an array of optogenetic manipulation techniques during in vivo electrophysiological experimentation. Interestingly, noxious stimulus evoked spinal neuronal firing was decreased upon opto-activation of A5 neurons (two-way ANOVA with Tukey post hoc, P < 0.0001). Hypothesizing that this may reflect activity in the noradrenergic diffuse noxious inhibitory control circuit, itself activated upon application of a conditioning stimulus, we opto-inhibited A5 neurons with concurrent conditioning stimulus application. Surprisingly, no spinal neuronal inhibition was observed; activity in the diffuse noxious inhibitory control circuit was abolished (two-way ANOVA, P < 0.0001). We propose that the A5 nucleus is a critical relay nucleus for mediation of diffuse noxious inhibitory controls. Given the plasticity of diffuse noxious inhibitory controls in disease, and its back and forward clinical translation, our data reveal a potential therapeutic target.
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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.