ArticleDiabetes2013
Rab7 silencing prevents μ-opioid receptor lysosomal targeting and rescues opioid responsiveness to strengthen diabetic neuropathic pain therapy.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Macrophage SH3 domain‑containing GRB2‑like protein B1 is required for Rab7‑mediated mitophagy in inflammation during sea water drowning acute lung injury.International journal of molecular medicine · 2026Article
- An SGLT2 inhibitor, canagliflozin, reduces blood glucose level in the renal capillaries and protects the capillary network in the diabetic rats.Diabetes, obesity & metabolism · 2025Article
- Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia.Metabolic brain disease · 2023Article
- Metformin prevents morphine-induced apoptosis in rats with diabetic neuropathy: a possible mechanism for attenuating morphine tolerance.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Knock-In Mouse Models to Investigate the Functions of Opioid ReceptorsFrontiers in cellular neuroscience · 2022Review
- Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.Nature communications · 2021Article
- Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Article
- Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Efficacy-Based Perspective to Overcome Reduced Opioid Analgesia of Advanced Painful Diabetic Neuropathy in Rats.Frontiers in pharmacology · 2019Article
- Neuropathic Pain Induced Alterations in the Opioidergic Modulation of a Descending Pain Facilitatory Area of the Brain.Frontiers in cellular neuroscience · 2019Article
- Dihydromyricetin Alleviates Diabetic Neuropathic Pain and Depression Comorbidity Symptoms by Inhibiting P2XFrontiers in psychiatry · 2019Article
- Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway.Neural regeneration research · 2018Article
- Effects of lncRNA uc.48+ siRNA on the release of CGRP in the spinal cords of rats with diabetic neuropathic pain.International journal of clinical and experimental pathology · 2017Article
- Thalidomide Promotes Morphine Efficacy and Prevents Morphine-Induced Tolerance in Rats with Diabetic Neuropathy.Neurochemical research · 2016Article
- Multiple Roles of the Small GTPase Rab7.Cells · 2016Review
- Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats.Heart and vessels · 2016Article
- The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice.Psychopharmacology · 2016Article
- Cellular localization and adaptive changes of the cardiac delta opioid receptor system in an experimental model of heart failure in rats.Heart and vessels · 2016Article
- Endomorphin-2 Inhibition of Substance P Signaling within Lamina I of the Spinal Cord Is Impaired in Diabetic Neuropathic Pain Rats.Frontiers in molecular neuroscience · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Painful diabetic neuropathy is poorly controlled by analgesics and requires high doses of opioids, triggering side effects and reducing patient quality of life. This study investigated whether enhanced Rab7-mediated lysosomal targeting of peripheral sensory neuron μ-opioid receptors (MORs) is responsible for diminished opioid responsiveness in rats with streptozotocin-induced diabetes. In diabetic animals, significantly impaired peripheral opioid analgesia was associated with a loss in sensory neuron MOR and a reduction in functional MOR G-protein-coupling. In control animals, MORs were retained mainly on the neuronal cell membrane. In contrast, in diabetic rats, they were colocalized with upregulated Rab7 in LampI-positive perinuclear lysosome compartments. Silencing endogenous Rab7 with intrathecal Rab7-siRNA or, indirectly, by reversing nerve growth factor deprivation in peripheral sensory neurons not only prevented MOR targeting to lysosomes, restoring their plasma membrane density, but also rescued opioid responsiveness toward better pain relief. These findings elucidate in vivo the mechanisms by which enhanced Rab7 lysosomal targeting of MORs leads to a loss in opioid antinociception in diabetic neuropathic pain. This is in contrast to peripheral sensory neuron MOR upregulation and antinociception in inflammatory pain, and provides intriguing evidence that regulation of opioid responsiveness varies as a function of pain pathogenesis.
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