ArticlePain2020
Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents.
Article in Pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 81 citations in OpenAlex.
- Divergence in μ and δ opioid receptor pharmacology in neurons and antinociceptive efficacy in neuropathic pain: Insights from MP135 and CYM51010.British journal of pharmacology · 2026Article
- Activation of µ-δ Opioid Receptor Heteromer Attenuates Chemotherapy-Induced Neuropathic Pain in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Dermorphin [D-Arg2, Lys4] (1-4) Amide Attenuates Burn Pain by Inhibiting TRPV1/NR2B Mediated Neuroinflammatory Signalling.Molecular neurobiology · 2025Article
- Mechanism and modulation of spontaneous pain: from neural circuits to drug development.Molecular biology reports · 2025Review
- Changes of intestinal microbiome and its relationship with painful diabetic neuropathy in rats.BMC microbiology · 2025Article
- PLGA nanoparticle-mediated anti-inflammatory gene delivery for the treatment of neuropathic pain.Nanomedicine (London, England) · 2025Article
- Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.Molecular neurobiology · 2025Article
- Mahuang Fuzi Xixin decoction: A potent analgesic for neuropathic pain targeting the NMDAR2B/CaMKIIα/ERK/CREB pathway.Heliyon · 2024Article
- Exploring viral neuropathic pain: Molecular mechanisms and therapeutic implications.PLoS pathogens · 2024Review
- Combination chemotherapy in rodents: a model for chemotherapy-induced neuropathic pain and pharmacological screening.Metabolic brain disease · 2024Article
- Peripheral mu-opioid receptor activation by dermorphin [D-Arg2, Lys4] (1-4) amide alleviates behavioral and neurobiological aberrations in rat model of chemotherapy-induced neuropathic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain.Journal of pain research · 2024Review
- Targeting sensory neuron GPCRs for peripheral neuropathic pain.Trends in pharmacological sciences · 2023Review
- Activation of the Mu-Delta Opioid Receptor Heteromers Blocks Morphine Rewarding Effects.The international journal of neuropsychopharmacology · 2023Article
- Surgically Induced Demyelination in Rat Sciatic Nerve.Brain sciences · 2023Article
- Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision.Journal of pain research · 2023Article
- Multifactorial pathways in burn injury-induced chronic pain: novel targets and their pharmacological modulation.Molecular biology reports · 2022Review
- Chronic constriction injury-induced changes in circular RNA expression profiling of the dorsal root ganglion in a rat model of neuropathic pain.BMC neuroscience · 2022Article
- Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain.International journal of molecular sciences · 2022Article
- Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats.Inflammopharmacology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Several reports support the idea that µ- and δ-opioid receptors (ORs) may exist as heterodimers in brain regions involved in pain signaling. The unique pharmacology of these heteromers may present a novel analgesic target. However, the role of µ-δ heteromers in sensory neurons involved in pain and opioid analgesia remains unclear, particularly during neuropathic pain. We examined the effects of spinal nerve injury on µ-δ heteromer expression in dorsal root ganglion (DRG) neurons and the effects of a µ-δ heteromer-targeting agonist, CYM51010, on neuropathic pain behavior in rats and mice. An L5 spinal nerve ligation (SNL) in rats significantly decreased µ-δ heteromer expression in L5 DRG but increased heteromer levels in uninjured L4 DRG. Importantly, in SNL rats, subcutaneous injection of CYM51010 inhibited mechanical hypersensitivity in a dose-related manner (EC50: 1.09 mg/kg) and also reversed heat hyperalgesia and attenuated ongoing pain (2 mg/kg, subcutaneously). HEK-293T cell surface-labeled with µ- and δ-ORs internalized both receptors after exposure to CYM51010. By contrast, in cells transfected with µ-OR alone, CYM51010 was significantly less effective at inducing receptor internalization. Electrophysiologic studies showed that CYM51010 inhibited the C-component and windup phenomenon in spinal wide dynamic range neurons of SNL rats. The pain inhibitory effects of CYM51010 persisted in morphine-tolerant rats but was markedly attenuated in µ-OR knockout mice. Our studies show that spinal nerve injury may increase µ-δ heterodimerization in uninjured DRG neurons, and that µ-δ heteromers may be a potential therapeutic target for relieving neuropathic pain, even under conditions of morphine tolerance.
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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.