ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 144 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Personalizing Perioperative Morphine Analgesia for Adolescents Undergoing Major Spine Surgeries
Double Blind Trial Investigating the Role of Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 403 citations in OpenAlex.
- Pharmacological interventions for preventing opioid-induced hyperalgesia in adults after opioid-based anesthesia: a systematic review and network meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients.The journal of pain · 2017Trial
- Peripartum pain management in opioid dependent women.European journal of pain (London, England) · 2012Trial
- Gabapentin improves cold-pressor pain responses in methadone-maintained patients.Drug and alcohol dependence · 2010Trial
- Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone-maintained patients.Addiction biology · 2008Trial
- Ceftriaxone suppresses the severity of paclitaxel-induced glutamate-mediated chronic pain in experimental animals.Scientific reports · 2025Article
- KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder.Pharmacology, biochemistry, and behavior · 2025Review
- Glycine Transporter 1 Inhibitors Minimize the Analgesic Tolerance to Morphine.International journal of molecular sciences · 2024Article
- Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Independent and joint contributions of physical disability and chronic pain to incident opioid use disorder and opioid overdose among Medicaid patients.Psychological medicine · 2024Article
- Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats.Pain reports · 2024Article
- Morphine induces HADHA succinylation, while HADHA desuccinylation alleviates morphine tolerance by influencing autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats.Frontiers in pharmacology · 2024Article
- The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.Frontiers in pharmacology · 2024Article
- Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use.International journal of molecular sciences · 2023Article
- Article
- Opioid-induced Neurotoxicity in Patients with Cancer Pain.Current treatment options in oncology · 2023Review
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- Lipophilic analogues of D-cysteine prevent and reverse physical dependence to fentanyl in male rats.Frontiers in pharmacology · 2023Article
- L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats.Frontiers in pharmacology · 2023Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we examined the role of spinal glutamate transporters (GTs) in the development of both morphine tolerance and associated thermal hyperalgesia. Chronic morphine administered through either intrathecal boluses or continuous infusion induced a dose-dependent downregulation of GTs (EAAC1 and GLAST) in the rat's superficial spinal cord dorsal horn. This GT downregulation was mediated through opioid receptors because naloxone blocked such GT changes. Morphine-induced GT downregulation reduced the ability to maintain in vivo glutamate homeostasis at the spinal level, because the hyperalgesic response to exogenous glutamate was enhanced, including an increased magnitude and a prolonged time course, in morphine-treated rats with reduced spinal GTs. Moreover, the downregulation of spinal GTs exhibited a temporal correlation with the development of morphine tolerance and thermal hyperalgesia. Consistently, the GT inhibitor l-trans-pyrrolidine-2-4-dicarboxylate (PDC) potentiated, whereas the positive GT regulator riluzole reduced, the development of both morphine tolerance and thermal hyperalgesia. The effects from regulating spinal GT activity by PDC were at least in part mediated through activation of the NMDA receptor (NMDAR), because the noncompetitive NMDAR antagonist MK-801 blocked both morphine tolerance and thermal hyperalgesia that were potentiated by PDC. These results indicate that spinal GTs may contribute to the neural mechanisms of morphine tolerance and associated abnormal pain sensitivity by means of regulating regional glutamate homeostasis.
Indexed as
Identifiers
12223586PMC6758088W1540277158What OpenQuestion holds
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.