ReviewTrends in pharmacological sciences2009
The "toll" of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia.
Review in Trends in pharmacological sciences, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
190 citing papers in PubMed, 1 synthesis or guideline pooled it, 421 citations in OpenAlex.
- Low Dose Naltrexone In The Management Of Chronic Pain Syndrome: A Meta-Analysis Of Randomized Controlled Clinical Trials.Current pain and headache reports · 2025Pooled it
- PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study.Psychopharmacology · 2020Trial
- Minocycline does not affect experimental pain or addiction-related outcomes in opioid maintained patients.Psychopharmacology · 2019Trial
- Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder.Psychopharmacology · 2018Trial
- The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users.Physiology & behavior · 2016Trial
- Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced Meditators.Psychosomatic medicineTrial
- The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.Journal of psychoactive drugsTrial
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Chemotherapy-Induced Neurotoxicity: Molecular Mechanisms, Biomarkers and Emerging Neuroprotective Strategies.Biomedicines · 2026Review
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- Water channel changes in astrocytes associated with buprenorphine administration in a rat model of diffuse traumatic brain injury.Research square · 2026Article
- Animal Models of Prenatal Opioid Exposure: Insights into Impaired Neurodevelopment.Advances in experimental medicine and biology · 2026Review
- BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.Frontiers in neuroscience · 2026Article
- Glial Activation, Neuroinflammation, and Loss of Neuroprotection in Chronic Pain: Cellular Mechanisms and Emerging Therapeutic Strategies.Biomedicines · 2025Review
- Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice.Scientific reports · 2025Article
- Knowledge, mechanisms, and intervention of the polytrauma clinical triad in military pain medicine.The Korean journal of pain · 2025Review
- Current and Evolving Concepts in the Management of Complex Regional Pain Syndrome: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Opioid System and Epithelial-Mesenchymal Transition.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Adolescent morphine exposure does not alter low-dose lipopolysaccharide (LPS)-induced sickness behavior in adult C57/BL6 mice.PloS one · 2025Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Glial activation participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products. Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression. Such effects can occur, not via classical opioid receptors, but rather via non-stereoselective activation of toll-like receptor 4 (TLR4), a recently recognized key glial receptor participating in neuropathic pain as well. This discovery identifies a means for separating the beneficial actions of opioids (opioid receptor mediated) from the unwanted side-effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug should be a stand-alone therapeutic for treating neuropathic pain as well. Excitingly, with newly-established clinical trials of two glial modulators for treating neuropathic pain and improving the utility of opioids, translation from rats-to-humans now begins with the promise of improved clinical pain control.
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What 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.