ArticlePain reports2016
The dark side of opioids in pain management: basic science explains clinical observation.
Article in Pain reports, 2016. 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 58 papers, 3 of them syntheses 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.
Bilateral Asymmetrical Erector Spinae Catheters Analgesia Versus Thoracic Epidural Catheter Analgesia in Minimally Invasive Oesophageal Cancer Surgery: a Randomized Controlled Trial
Benefit of Acupuncture Combined to Regional Analgesia for Post Operative Pain Relief After Hysterectomy
Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Shedding light on pain management: a translational systematic review of light therapy for the treatment of chronic pain.EBioMedicine · 2026Pooled it
- Does aerobic exercise effect pain sensitisation in individuals with musculoskeletal pain? A systematic review.BMC musculoskeletal disorders · 2022Pooled it
- Opioid prescription patterns in Germany and the global opioid epidemic: Systematic review of available evidence.PloS one · 2019Pooled it
- Circadian rhythmicity and biopsychosocial characteristics influence opioid use in chronic low back pain.The Journal of clinical investigation · 2025Trial
- Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial.BMC anesthesiology · 2022Trial
- Effect of intraperitoneal bupivacaine vs magnesium sulfate on early postoperative outcomes after laparoscopic sleeve gastrectomy: a randomized clinical trial.Perioperative medicine (London, England) · 2025Article
- The effect of workload on primary care doctors on referral rates and prescription patterns: evidence from English NHS.The European journal of health economics : HEPAC : health economics in prevention and care · 2025Article
- FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia.Nature communications · 2024Article
- Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.Current pain and headache reports · 2024Review
- Safety and efficacy of ketorolac continuous infusion for multimodal analgesia of vaso-occlusive crisis in patients with sickle cell disease.Orphanet journal of rare diseases · 2024Article
- Microglial inflammation modulates opioid analgesic tolerance.Journal of neuroscience research · 2023Review
- Pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews.The Cochrane database of systematic reviews · 2023Review
- Peripheral Regional Anesthesia Using Local Anesthetics: Old Wine in New Bottles?Journal of clinical medicine · 2023Review
- The mechanisms and management of persistent postsurgical pain.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- The heavy-tailed valence hypothesis: the human capacity for vast variation in pleasure/pain and how to test it.Frontiers in psychology · 2023Article
- A scoping review of outpatient interventions to support the reduction of prescription opioid medication for chronic non cancer pain.Journal of clinical nursing · 2022Article
- Early Initiation of Sub-Anesthetic Ketamine Infusion in Adults with Vaso-Occlusive Crises Is Associated with Greater Reduction in Sickle Cell Pain Intensity: A Single Center's Experience.Pain medicine (Malden, Mass.) · 2022Article
- The Effect of State-Level Prescription Opioid Legislation on Patient Outcomes After Lumbar Tubular Microdecompression.International journal of spine surgery · 2022Article
- Chronic Cancer Pain: Opioids within Tumor Microenvironment Affect Neuroinflammation, Tumor and Pain Evolution.Cancers · 2022Review
- Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Phase 3 Trials of Baricitinib.ACR open rheumatology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIn the past 2 decades, opioids have been used increasingly for the treatment of persistent pain, and doses have tended to creep up. As basic science elucidates mechanisms of pain and analgesia, the cross talk between central pain and opioid actions becomes clearer.
objectivesWe aimed to examine the published literature on basic science explaining pronociceptive opioid actions, and apply this knowledge to clinical observation.
methodsWe reviewed the existing literature on the pronociceptive actions of opioids, both preclinical and clinical studies.
resultsBasic science provides a rationale for the clinical observation that opioids sometimes increase rather than decrease pain. Central sensitization (hyperalgesia) underlies pain chronification, but can also be produced by high dose and high potency opioids. Many of the same mechanisms account for both central pain and opioid hyperalgesia.
conclusionNewly revealed basic mechanisms suggest possible avenues for drug development and new drug therapies that could alter pain sensitization through endogenous and exogenous opioid mechanisms. Recent changes in practice such as the introduction of titration-to-effect for opioids have resulted in higher doses used in the clinic setting than ever seen previously. New basic science knowledge hints that these newer dosing practices may need to be reexamined. When pain worsens in a patient taking opioids, can we be assured that this is not because of the opioids, and can we alter this negative effect of opioids through different dosing strategies or new drug intervention?
Indexed as
Identifiers
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.