SCN9A Gene Expression and Inflammatory Cytokines

NCT07532200 | Not Yet Recruiting

• 1 other identifier: SCN9A IRRC- 173
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Voltage-gated sodium channels, especially Nav1.7 encoded by the SCN9A gene, are key regulators of nociceptive transmission. Upregulation of SCN9A has been associated with increased neuronal excitability and heightened pain perception. In parallel, inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) are known to sensitize peripheral nociceptors and reduce the efficacy of local anesthetics by modifying tissue environment and ion channel activity. However, the combined influence of SCN9A expression and inflammatory cytokines on anesthetic success in SIP has not been fully elucidated. This prospective case-control study aims to evaluate the association between SCN9A gene expression and inflammatory cytokine levels with the clinical success of IANB in patients with SIP affecting mandibular molars. Approximately 90-100 patients will be recruited and categorized into two groups based on anesthetic outcome: successful anesthesia and failed anesthesia. All patients will receive a standardized IANB using 2% lidocaine with 1:100,000 epinephrine. Anesthetic success will be determined based on the absence of pain during access cavity preparation and instrumentation. Following access and pulp extirpation, pulpal tissue samples will be collected. SCN9A gene expression will be assessed using quantitative real-time polymerase chain reaction (RT-qPCR), with relative expression calculated using the 2\^-ΔΔCt method. Inflammatory cytokine levels (IL-6, TNF-α, IL-1β) will be quantified using enzyme-linked immunosorbent assay (ELISA). The primary outcome will be the difference in SCN9A expression between failed and successful anesthesia groups. Secondary outcomes will include comparison of cytokine levels and evaluation of correlations between SCN9A expression and inflammatory markers. Statistical analysis will include group comparisons, correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis to assess the predictive value of these biomarkers.

Conditions

Pulpitis - Irreversible

Keywords

Symptomatic irreversible pulpitis; Inferior alveolar nerve block; Gene expression; RT-qPCR; Inflammatory cytokines

Outcome Measures

Primary Outcomes (1)

• Success of Inferior Alveolar Nerve Block (IANB)

  The primary outcome will be the clinical success of the inferior alveolar nerve block (IANB), assessed during endodontic access cavity preparation and initial instrumentation. Anesthetic success will be defined as the absence of pain or the presence of only mild pain that does not require any supplementary anesthetic intervention. Anesthetic failure will be defined as the presence of moderate to severe pain necessitating additional anesthesia (e.g., intraligamentary or intrapulpal injection).

  Assessed 15 minutes after administration of IANB, during access cavity preparation and initial instrumentation at the same visit

Study Arms (2)

IANB Success (Adequate Anesthesia) Group

This cohort will include patients with symptomatic irreversible pulpitis in mandibular molars who achieve successful pulpal anesthesia following administration of a standardized inferior alveolar nerve block (IANB) using 2% lidocaine with 1:100,000 epinephrine. Anesthetic success will be defined as the absence of pain (no or mild pain) during access cavity preparation and initial instrumentation without the need for any supplementary anesthetic techniques. Following confirmation of anesthesia, access cavity preparation and pulp extirpation will be performed, and pulpal tissue samples will be collected for analysis of SCN9A gene expression (RT-qPCR) and inflammatory cytokine levels (IL-6, TNF-α, IL-1β) using ELISA.

Procedure: Inferior Alveolar Nerve Block

IANB Failure (Inadequate Anesthesia) Group

This cohort will include patients with symptomatic irreversible pulpitis in mandibular molars who experience inadequate pulpal anesthesia following administration of a standardized inferior alveolar nerve block (IANB) using 2% lidocaine with 1:100,000 epinephrine. Anesthetic failure will be defined as the presence of moderate to severe pain during access cavity preparation or instrumentation, necessitating the use of supplementary anesthetic techniques (e.g., intraligamentary or intrapulpal injections). Pulpal tissue samples will be collected after access cavity preparation and pulp extirpation for analysis of SCN9A gene expression (RT-qPCR) and inflammatory cytokines (IL-6, TNF-α, IL-1β) using ELISA.

Procedure: Inferior Alveolar Nerve Block

Interventions

Inferior Alveolar Nerve Block PROCEDURE

All participants will receive a standardized inferior alveolar nerve block (IANB) administered using 2% lidocaine with 1:80,000 epinephrine. The injection will be performed using a conventional Halsted technique with a 27-gauge long needle under strict aseptic conditions. The needle will be inserted at the pterygomandibular raphe region, advancing until bony contact is achieved near the mandibular foramen. Following negative aspiration, approximately 1.8 mL of anesthetic solution will be deposited slowly over 60-90 seconds. Lip numbness will be assessed after 10-15 minutes to confirm nerve block onset. No additional anesthetic techniques will be used prior to the assessment of primary anesthetic success. Endodontic access cavity preparation will then be initiated, and pain response during access and initial instrumentation will be recorded using a standardized pain scale. Anesthetic success or failure will be determined based on the patient's pain response, as per predefined criteria.

IANB Failure (Inadequate Anesthesia) Group; IANB Success (Adequate Anesthesia) Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult patients presenting to the postgraduate endodontic clinic with symptomatic irreversible pulpitis in mandibular first or second molars requiring root canal treatment. Eligible participants will be systemically healthy (ASA I or II), aged between 18 and 60 years, and will report moderate to severe preoperative pain. Diagnosis will be established based on clinical findings, including spontaneous pain, prolonged response to cold testing, and absence of periapical pathology requiring surgical intervention.

You may qualify if:

• Patients aged 18-60 years
• Systemically healthy individuals (ASA I or II)
• Presence of a mandibular first or second molar diagnosed with symptomatic irreversible pulpitis
• Vital tooth confirmed by positive response to pulp sensibility tests (cold test/EPT)
• Moderate to severe preoperative pain (Heft-Parker VAS)
• Patients requiring endodontic treatment under inferior alveolar nerve block
• Ability and willingness to provide informed consent

You may not qualify if:

• Patients who have taken analgesics, anti-inflammatory drugs, or antibiotics within the last 48 hours
• Presence of systemic diseases affecting pain perception or inflammation (e.g., diabetes, neuropathic disorders)
• Pregnant or lactating women
• Teeth with periapical abscess, swelling, or sinus tract
• Non-vital teeth or teeth with previous endodontic treatment
• Patients with known allergy to local anesthetic agents
• Patients with limited mouth opening or anatomical conditions affecting IANB administration
• Inability to understand pain assessment scales or comply with study protocol

Sponsors & Collaborators

• Jamia Millia Islamia: lead

Study Sites (1)

Faculty of Dentistry

New Delhi, National Capital Territory of Delhi, 110025, India

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biological samples will be collected from patients diagnosed with symptomatic irreversible pulpitis undergoing endodontic treatment. The primary biospecimen will be vital pulpal tissue, obtained aseptically immediately after access cavity preparation and pulp extirpation. The collected pulp tissue will be divided into two portions: one portion will be preserved in RNA stabilization solution for subsequent RNA extraction and gene expression analysis of SCN9A; the second portion will be processed for protein extraction and stored appropriately for the estimation of inflammatory cytokines (IL-6, TNF-α, IL-1β) using enzyme-linked immunosorbent assay (ELISA). All samples will be de-identified and labeled with unique study codes to ensure confidentiality. Biospecimens will be stored under controlled laboratory conditions and used exclusively for the purposes of this study. No genetic will be used for purposes beyond those outlined in the study protocol without additional ethical approval.

Central Study Contacts

Vivek Aggarwal, MDS

CONTACT

01126983646; vaggarwal@jmi.ac.in

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start: April 10, 2026
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)