ArticleThe Journal of physiology2012
Endocannabinoid-dependent plasticity at spinal nociceptor synapses.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Role of Concentration in Opposing Effects of Anandamide on Nociceptive Synapses versus Non-nociceptive Synapses.eNeuro · 2026Article
- Injury alters sensory, motor, and integrative elements underlying operant conditioning in the medicinal leech.PloS one · 2025Article
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana.Neurochemical research · 2024Article
- Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level.Physiological research · 2024Review
- Lysophosphatidic Acid Receptors LPAR5 and LPAR2 Inversely Control Hydroxychloroquine-Evoked Itch and Scratching in Mice.International journal of molecular sciences · 2024Article
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana.Research square · 2024Article
- Reactive spinal glia convert 2-AG to prostaglandins to drive aberrant astroglial calcium signaling.Frontiers in cellular neuroscience · 2024Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Heterosynaptic long-term potentiation of non-nociceptive synapses requires endocannabinoids, NMDARs, CamKII, and PKCζ.Journal of neurophysiology · 2023Article
- Serotonin mediates stress-like effects on responses to non-nociceptive stimuli in the medicinal leech Hirudo verbana.The Journal of experimental biology · 2022Article
- Approaches to studying injury-induced sensitization and the potential role of an endocannabinoid transmitter.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2022Article
- Activity-Dependent Modulation of Tonic GABA Currents by Endocannabinoids inFrontiers in synaptic neuroscience · 2022Article
- Lights on Endocannabinoid-Mediated Synaptic Potentiation.Frontiers in molecular neuroscience · 2020Review
- Comparative studies of endocannabinoid modulation of pain.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Endocannabinoid-mediated potentiation of nonnociceptive synapses contributes to behavioral sensitization.Journal of neurophysiology · 2018Article
- Acetaminophen Relieves Inflammatory Pain through CBThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli.Scientific reports · 2017Article
- Comparative biology of pain: What invertebrates can tell us about how nociception works.Journal of neurophysiology · 2017Review
- Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Neuroplastic changes at the spinal synapses between primary nociceptors and second order dorsal horn neurons play key roles in pain and analgesia. NMDA receptor-dependent forms of long-term plasticity have been studied extensively at these synapses, but little is known about possible contributions of the endocannabinoid system. Here, we addressed the role of cannabinoid (CB)1 receptors in activity-dependent plasticity at these synapses. We report that conditional low-frequency stimulation of high-threshold primary sensory nerve fibres paired with depolarisation of the postsynaptic neuron evoked robust long-term depression (LTD)of excitatory synaptic transmission by about 40% in the vast majority (90%) of recordings made in wild-type mice. When recordings were made from global or nociceptor-specific CB(1) receptor-deficient mice (CB(1) (−/− ) mice and sns-CB(1)(−/−) mice), the portion of neurons exhibiting LTD was strongly reduced to about 25%. Accordingly, LTD was prevented to a similar extent by the CB1 receptor antagonist AM251 and mimicked by pharmacological activation of CB1 receptors. In a subset of neurons with EPSCs of particularly high stimulation thresholds, we furthermore found that the absence of CB(1) receptors in CB(1)(−/−) and sns-CB(1)(−/−) mice converted the response to the paired conditioning stimulation protocol from LTD to long-term potentiation (LTP). Our results identify CB1 receptor-dependent LTD as a form of synaptic plasticity previously unknown in spinal nociceptors. They furthermore suggest that prevention of LTP may be a second hither to unknown function of CB1 receptors in primary nociceptors. Both findings may have important implications for our understanding of endogenous pain control mechanisms and of analgesia evoked by cannabinoid receptor agonists.
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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.