Cytokine Alterations and Chronic Post-Surgical Pain

NCT06418295 | Not Yet Recruiting

• 1 other identifier: CPSP Epigenetics
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Chronic Post-Surgical Pain (CPSP) is a condition that involves experiencing pain and/or discomfort that lasts for more than 3 months following surgery without any explainable cause of this pain such chronic infection or pain caused from a condition preceding surgery. This condition negatively impacts health related quality of life and is associated with significant financial burden both for the patient and health care system. Patients undergoing common surgeries such as amputation, breast surgery, hernia repair, coronary artery bypass, and caesarean section can be prone to developing CPSP. CPSP may be caused by the release and expression of different cellular molecules called cytokines and chemokines that can cause a pain response when they are present in the body at certain levels. After surgical incision, tissue cells have been shown to release cytokines and chemokines, thus increasing the concentration of these molecules in the patient's blood. It is not entirely known what mechanisms cause the increased expression of chemokines and cytokines. One method that may play a role in in this expression is epigenetics which is the alteration of gene expression without permanently altering the structure of DNA. Unlike mutations, epigenetic changes are dynamic, possibly reversible, and are influenced by environmental and behavioral changes such as diet, exercise, disease, stress, toxin exposure etc. Epigenetic changes occur all throughout our life and have been associated with several disease processes such as cancer, diabetic complications, and chronic pain. At the molecular level, certain events take place that can regulate (increase or decrease) the expression of cytokines and chemokines, most notably DNA methylation of their promotor (which involves adding molecules to DNA that does not change its structure but changes it's activity). The investigators are conducting this study to determine if the alteration of specific cytokines are associated with the occurrence of CPSP and whether these cytokines are regulated by DNA methylation at their promoter. This study will take place at London Health Sciences Centre and will recruit up to 60 patients who will be undergoing a thoracotomy procedure (surgery of the chest area).

Conditions

Chronic Post Operative Pain

Keywords

chronic pain; epigentics

Outcome Measures

Primary Outcomes (3)

• Identification of temporal alterations of cytokines in patients with CPSP.

  Cellular assays will be performed on blood samples obtained pre-and postoperatively to determined the level of expression of certain chemokines, cytokines, and growth factors that have been shown to be potentially related to CPSP. Pre and postoperative results will be compared to determine the association that each may have on the development of CPSP.

  3 months

• Identification of specific DNA promoter methylation regulating production of specific cytokines

  Cellular assays will be performed on blood samples obtained pre-and postoperatively to determine if DNA promotor methylation is associated with changes in expression of the cytokines being investigated. Pre and postoperative results will be compared to determine the impact that this potential epigenetic change (DNA promotor methylation) may have on the development of CPSP.

  3 months

• Generate initial data to determine the sample size needed to adequately power a larger trial

  As this is a pilot study, data will be analyzed to determine the sample size needed to power a larger, randomized controlled trial.

  3 months

Study Arms (1)

Unilateral thoracotomy

Unilateral thoracotomy to proceed according to standard of care guidelines.

Other: Unilateral thoracotomy

Interventions

Unilateral thoracotomy OTHER

Unilateral thoracotomy to proceed as per standard of care guidelines. Thoracic epidural analgesia, or patient controlled analgesia (PCA) pumps will be offered to each study participant as per standard of care. Pre- and post-operative (post-operative day 1 and 3 months) pain scores and blood samples will be collected. Blood samples will be analyzed to determine the concentration of cytokines, chemokines, and growth factors that are potentially associated with CPSP (epidermal growth factor, eotaxin, fibroblast growth factor basic, G-CSF, GM-CSF, human growth factor, IFN-α, IFN-γ, IL-1ra, IL-1β, IL-2, IL-2r, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α, and VEGF). DNA promotor methylation for these targets will also be investigated.

Unilateral thoracotomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients scheduled to undergo thoracotomy for malignancy at Victoria Hospital, London Health Science Centre.

You may qualify if:

• years of age or older
• Undergoing unilateral thoracotomy for the first time on that side
• Willing to provide informed consent for study participation.
• Patient with malignancy that needs thoracotomy for surgical resection.

You may not qualify if:

• Chronic pain prior to surgery
• Pre-existing fibromyalgia
• Long-term opioid use
• Diabetes mellitus
• Inflammatory bowel disease
• Pre-existing neurological disease
• Pre-existing nerve injury
• Evidence of dementia, delirium or cognitive disorder that may interfere with study participation
• Malignancy other than lung cancer
• Autoimmune disorder (e.g. rheumatoid arthritis and psoriatic arthritis)
• Pregnancy
• Inability to communicate in the English language (required for completion of questionnaires and provision of pain scores).
• Patents on antiepileptic medications

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Related Publications (6)

• Macrae WA, Davies HTO, Crombie IK, Linton S, Croft P, Von Korff M, LeResche L. Chronic postsurgical pain, Epidemiology of Pain, 1999, Seattle International Association for the Study of Pain (pg. 125-42)

  BACKGROUND

• Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008 Jul;101(1):77-86. doi: 10.1093/bja/aen099. Epub 2008 Apr 22.

  PMID: 18434337 BACKGROUND

• Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.

  PMID: 29738328 BACKGROUND

• Aroke EN, Joseph PV, Roy A, Overstreet DS, Tollefsbol TO, Vance DE, Goodin BR. Could epigenetics help explain racial disparities in chronic pain? J Pain Res. 2019 Feb 18;12:701-710. doi: 10.2147/JPR.S191848. eCollection 2019.

  PMID: 30863142 BACKGROUND

• Descalzi G, Ikegami D, Ushijima T, Nestler EJ, Zachariou V, Narita M. Epigenetic mechanisms of chronic pain. Trends Neurosci. 2015 Apr;38(4):237-46. doi: 10.1016/j.tins.2015.02.001. Epub 2015 Mar 9.

  PMID: 25765319 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (7 mL) collected at the following time points: 1. Pre-operatively before surgery. 2. Post-operative day 1 following surgery 3. 3 months following surgery

MeSH Terms

Conditions

Pain, Postoperative; Chronic Pain

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Abhijit Biswas

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abhijit Biswas

CONTACT

5196858500; Abhijit.Biswas@lhsc.on.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anesthesiologist, Associate Professor

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 17, 2024
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share