Evidence map›Paper›PMID 40645792›Full record

ArticleInternational journal of spine surgery2025

Opioid-Induced Hyperalgesia and Inflammaging in the Management of Spine Pain: The Case for Genetically Directed Dopamine Homeostasis.

Kai-Uwe Lewandrowski, Rossano Kepler Alvim Fiorelli, Sergio Schmidt, Alireza Sharafshah, David Baron, Mark S Gold, Panayotis K Thanos, Igor Elman, Debasis Bagchi, Abdalla Bowirrat and 3 more

Abstract read
In one paragraph

Article in International journal of spine surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Kai-Uwe LewandrowskiDepartment of Orthopedics, University of Arizona, Banner Medical Center, Tucson, Arizona, USA business@tucsonspine.com.ORCID http://orcid.org/0000-0001-7842-2914
Rossano Kepler Alvim FiorelliDepartment of Thoracic Surgery, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.ORCID http://orcid.org/0000-0001-5236-0903
Sergio SchmidtDepartment of Neuroscience, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.ORCID http://orcid.org/0000-0001-7654-5507
Alireza SharafshahCellular and Molecular Research Center - Independent Department at Guilan University of Medical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Guilan, Iran.ORCID http://orcid.org/0000-0001-8048-9587
David BaronCambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7670-2613
Mark S GoldDivision of Addiction Research and Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA.ORCID http://orcid.org/0000-0001-7138-8047
Panayotis K ThanosDepartment of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA.ORCID http://orcid.org/0000-0002-5663-3478
Igor ElmanDepartment of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1345-2677
Debasis BagchiDepartment of Pharmaceutical Sciences, Texas Southern University College of Pharmacy, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6661-8071
Abdalla BowirratDepartment of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.ORCID http://orcid.org/0000-0002-6823-4466
Albert PinhasovDepartment of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.ORCID http://orcid.org/0000-0001-8116-4565
Morgan P LorioAdvanced Orthopedics, Altamonte Springs, FL, USA.ORCID http://orcid.org/0000-0003-1623-2095
Kenneth BlumCambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6727-803X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe management of spine-related pain with narcotics, both before and after surgery, poses major challenges, including drug diversion, limited effectiveness, and worsening of pain symptoms over time. Chronic opioid use is associated with hypodopaminergia-induced hyperalgesia, whereby dopamine depletion increases pain sensitivity. Patients with inherently low dopaminergic function are particularly predisposed to hyperalgesia and reduced pain tolerance.

methodsAn alternative therapeutic strategy centers on genetically guided pro-dopamine regulation, which aims to transmodulate dopaminergic signaling to mitigate hyperalgesia. Early identification of predisposition through genetic testing, combined with pharmacogenetic and pharmacogenomic monitoring, is proposed to optimize treatment approaches.

resultsPro-dopamine regulators have demonstrated promising results across 43 clinical studies, showing potential to reduce stress, craving, and relapse rates, while improving emotional well-being and attenuating pain sensitivity. These findings suggest that pro-dopamine regulation may serve as a viable frontline therapy for managing chronic pain and associated Reward Deficiency Syndrome behaviors, offering a significant reduction in the adverse effects commonly observed with chronic opioid therapy.

conclusionsGiven the limitations of dopaminergic blockade through chronic opioid agonist therapy, there is a critical need to reevaluate current pain management practices. The induction of dopamine homeostasis via pro-dopamine regulation represents a novel and potentially transformative strategy. Spine surgeons, pain specialists, and addiction medicine practitioners are urged to consider this approach as a promising alternative for improving long-term outcomes in patients suffering from chronic pain.

Indexed as

chronic paindopamine homeostasisdopaminergic signalinghyperalgesiahypodopaminergiaopioid analgesicsprecisiontransmodulation

Identifiers

PMID40645792
PMCPMC12570064

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.