ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Opioids disrupt pro-nociceptive modulation mediated by raphe magnus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Deconstruction of a spino-brain-spinal cord circuit drives chronic mechanical pain.Research square · 2025Article
- Offset analgesia as a marker of dysfunctional pain modulation in episodic and chronic migraine.The journal of headache and pain · 2025Article
- Cell type-specific dissection of sensory pathways involved in descending modulation.Trends in neurosciences · 2023Review
- Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit.Brain : a journal of neurology · 2022Article
- Responses of neurons in rostral ventromedial medulla to nociceptive stimulation of craniofacial region and tail in rats.Brain research · 2021Article
- Mechanisms, diagnosis, prevention and management of perioperative opioid-induced hyperalgesia.Pain management · 2021Article
- Effect of Expectation on Pain Processing: A Psychophysics and Functional MRI Analysis.Frontiers in neuroscience · 2020Article
- Changes in Brainstem Pain Modulation Circuitry Function over the Migraine Cycle.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Article
- Identification of a novel spinal nociceptive-motor gate control for Aδ pain stimuli in rats.eLife · 2017Article
- Entanglement between thermoregulation and nociception in the rat: the case of morphine.Journal of neurophysiology · 2016Article
- Article
- Cat's medullary reticulospinal and subnucleus reticularis dorsalis noxious neurons form a coupled neural circuit through collaterals of descending axons.Journal of neurophysiology · 2016Article
- CO2-inhibited neurons in the medullary raphé are GABAergic.Respiratory physiology & neurobiology · 2014Article
- The selectivity of rostroventral medulla descending control of spinal sensory inputs shifts postnatally from A fibre to C fibre evoked activity.The Journal of physiology · 2014Article
- Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- The consequences of pain in early life: injury-induced plasticity in developing pain pathways.The European journal of neuroscience · 2014Review
- Medullary circuits for nociceptive modulation.Current opinion in neurobiology · 2012Review
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
In anesthetized rats, opioid analgesia is accompanied by a specific pattern of tonic activity in two neuronal populations within the medullary raphe magnus (RM): opioids silence pain-facilitatory ON cells and produce sustained discharge in pain-inhibitory OFF cells. These tonic activity patterns, hypothesized to generate a tonic analgesic state, have not been observed in recordings made without anesthesia. Therefore, we recorded ON and OFF cell activity before and after an analgesic dose of morphine in unanesthetized mice. The tonic activity of ON and OFF cells was unchanged by morphine. Rather, morphine suppressed the phasic ON cell excitation and OFF cell inhibition evoked by noxious stimulation. Before morphine, the magnitude of the noxious stimulus-evoked burst in ON cells correlated with motor withdrawal magnitude, suggesting that ON cells facilitate nocifensive motor reactions. Contrary to model prediction, OFF cell activity was greater before stimulus trials that evoked withdrawals than those without withdrawals. Since withdrawals only occurred when OFF cell activity was suppressed, a decrease in OFF cell activity appears to serve as a pro-nociceptive signal that synchronizes and therefore strengthens the ensuing motor reaction. We further propose that morphine acts in RM to suppress ON and OFF cell phasic responses and thereby disable RM's pro-nociceptive output. Thus, RM cells produce antinociception by failing to exert the pro-nociceptive effects normally engaged by noxious stimulation. These findings revise the conventional understanding of supraspinal opioid analgesia and demonstrate that RM produces on demand rather than state modulation, allowing RM cells to serve other functions during pain-free periods.
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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.