Mar 18, 2026

Public workspaceAssociation Between SCN Gene Polymorphisms and Postoperative Pain Intensity and Analgesic Response: A Systematic Review

DOI
https://dx.doi.org/10.17504/protocols.io.14egn5rzmg5d/v1
  • Camille Racca1,
  • Julia Franken2,
  • Ada Du Pasquier1,
  • Marion Cahen1,
  • Ihssene Djidjeli2
  • 1Pitié-Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;
  • 2Clinical Research Committee, Rare Disease Pain Network (REDOMA), Paris, France.
Camille Racca
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DOI: https://dx.doi.org/10.17504/protocols.io.14egn5rzmg5d/v1
Protocol Citation: Camille Racca, Julia Franken, Ada Du Pasquier, Marion Cahen, Ihssene Djidjeli 2026. Association Between SCN Gene Polymorphisms and Postoperative Pain Intensity and Analgesic Response: A Systematic Review. protocols.io https://dx.doi.org/10.17504/protocols.io.14egn5rzmg5d/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: March 17, 2026
Last Modified: March 18, 2026
Protocol Integer ID: 313427
Keywords: association between scn gene polymorphism, interindividual variability in postoperative pain, scn gene polymorphism, role of scn gene polymorphism, postoperative pain outcome, postoperative pain intensity, postoperative pain, analgesic response, germline genetic variant, genetic variant, postoperative setting
Abstract
This protocol describes a systematic review investigating the association between SCN gene polymorphisms and postoperative pain and analgesic response.

The review will synthesize available evidence on the relationship between these germline genetic variants and postoperative pain outcomes, as well as treatment effectiveness and safety in the postoperative setting.

The expected results will provide a comprehensive synthesis of current evidence and help clarify the role of SCN gene polymorphisms in interindividual variability in postoperative pain and analgesic response.
Guidelines
This systematic review will be conducted and reported in accordance with the PRISMA guidelines. As the review will include primarily observational studies, the reporting quality of included studies will also be considered in light of the STROBE recommendations.
Materials
The following materials and resources will be required for the conduct of this systematic review:
  • Access to bibliographic databases: PubMed/MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL)
  • Reference management software for citation storage and duplicate removal (e.g., Zotero, EndNote, or Mendeley)
  • Screening and systematic review management software (e.g., Rayyan, Covidence, or similar tools)
  • Data extraction forms developed for the review (spreadsheet or database format)
  • Risk of bias assessment tools, including the Joanna Briggs Institute (JBI) critical appraisal checklists
  • Access to statistical and data management software if required (e.g., R, Jamovi, or similar software)
Troubleshooting
Review question
Among surgical patients, what is the association between SCN gene polymorphisms and postoperative pain outcomes, including pain intensity, severe postoperative pain, and analgesic response?
Secondary Objectives
To evaluate the association between SCN gene polymorphisms and analgesic response, including analgesic requirements, dose escalation, and treatment effectiveness.
To evaluate the association between SCN gene polymorphisms and the incidence of severe postoperative pain.
To evaluate the association between SCN gene polymorphisms and the occurrence of treatment-related adverse effects, particularly opioid-related side effects.
To evaluate the association between SCN gene polymorphisms and the incidence of chronic postoperative pain.
Population
This review will include studies involving adult and pediatric patients undergoing all types of surgical procedures.

Types of Interventions
All pharmacological treatments used in the management of postoperative pain will be considered eligible, without restriction on drug class, dose, or route of administration. These include, but are not limited to:
  • opioids
  • non-opioid analgesics (e.g., paracetamol, NSAIDs)
  • local anesthetics
  • adjuvant analgesics (e.g., antidepressants, anticonvulsants)
  • multimodal analgesic regimens
Types of studies
Included studies
The review will include the following study designs:
  • randomized controlled trials;
  • non-randomized interventional studies;
  • prospective and retrospective cohort studies;
  • case–control studies;
  • analytical cross-sectional studies;
  • case series including at least five participants.e
Excluded studies

The following types of publications will be excluded:
  • animal studies;
  • in vitro studies;
  • expert opinions;
  • narrative reviews;
  • editorials and commentaries;
  • conference abstracts for which sufficient data cannot be extracted.

Search Strategy
A comprehensive literature search will be conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of controlled vocabulary (e.g., MeSH and Emtree terms) and free-text keywords related to postoperative pain, SCN gene polymorphisms, and pharmacogenetics.
The search strategy will be adapted for each database.
Reference lists of included studies and relevant reviews will also be screened to identify additional eligible studies.
Screening strategy
All retrieved records will be imported into a reference management software and duplicates will be removed.
The study selection process will consist of two stages:
  1. Title and abstract screening
  2. Full-text eligibility assessment
Each stage will be performed independently by two reviewers.
Disagreements will be resolved through discussion or consultation with a third reviewer.
The study selection process will be reported using a PRISMA flow diagram.
Data Management
Extracted data will include:
  • study characteristics (e.g., year of publication, country, study design)
  • participant characteristics (e.g., age, sex, type of surgery)
  • type of surgical procedure
  • postoperative pain characteristics (e.g., timing, assessment conditions)
  • pharmacological treatments evaluated
  • SCN gene polymorphisms analyzed (e.g., gene, SNPs)
  • outcome measures (e.g., pain intensity, analgesic consumption)
  • effect estimates and statistical results
Data extraction will be conducted independently by two reviewers.
Statistical Methods
A narrative synthesis will be conducted to summarize the evidence regarding the association between SCN gene polymorphisms and postoperative pain outcomes and analgesic response.

Given the expected heterogeneity in genetic variants, pharmacological treatments, surgical procedures, and outcome measures, a meta-analysis is not planned.

Findings will be summarized using a structured narrative approach, highlighting associations between specific SCN gene variants and postoperative pain intensity and analgesic response.
Risk of Bias Assessment
Risk of bias will be assessed independently by two reviewers using the Joanna Briggs Institute (JBI) critical appraisal checklists, according to the study design.
The appropriate JBI checklist will be applied for each study type, including:
  • randomized controlled trials
  • cohort studies
  • case–control studies
  • cross-sectional studies
  • case series
Disagreements between reviewers will be resolved through discussion or consultation with a third reviewer.
The results of the risk of bias assessment will be presented in tabular form.
Support and Funding
This review is supported by DRAW YOUR FIGHT, a nonprofit organization dedicated to raising awareness of invisible disabilities and chronic pain, and to promoting research through collaboration between patients and medical experts. The review received no specific external funding
Protocol references
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–1457.

Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: Joanna Briggs Institute; 2020.

Dib-Hajj SD, Yang Y, Black JA, Waxman SG. The NaV1.7 sodium channel: from molecule to man. Nat Rev Neurosci. 2013;14(1):49–62.

Reimann F, Cox JJ, Belfer I, Diatchenko L, Zaykin DV, McHale DP, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A. 2010;107(11):5148–5153.
Acknowledgements
The authors acknowledge the support of their institutions and colleagues who contributed to methodological discussions during the development of this protocol.