Sensory Outcomes in Active Substance Users

Molecular and Behavioral Characterization of Post-Operative Sensory Outcomes in Individuals With Chronic Pain or Persistent Opioid Use

The incidence and severity of postoperative pain after spine surgery are notably high, often requiring intensive management and potentially affecting the patient's recovery, satisfaction, and long-term outcomes. Post-operative pain is particularly difficult to manage in patients with substance use disorder likely due to a combination of withdrawal symptoms and molecular changes in the pain matrix. Opiates are the leading cause of overdose related fatalities, and carry a significant burden of substance related morbidity and mortality. As over 80% of patients undergoing low-risk surgery receive opioid prescriptions, the investigators aim to identify unique molecular characteristics of pain within current and previous opioid users, which have been understudied in this context. This study also seeks to understand the molecular mechanisms underlying worsened postoperative pain in patients with opioid use disorder (OUD).

Flow cytometry analysis of human serum will be done, which will assess circulating immune cells that can contribute to exacerbated surgery site inflammation. Spatial profiling of gene expression will be done in the dermis using Visium slide sequencing, focusing on the interplay between nerve endings, resident immune cells, and supporting dermal cells, all of which collectively contribute to the sensation pain. Both the visual pain rating scale and McGill Pain Questionnaire will be used to comprehensively quantify pain outcomes during the participant's postoperative recovery stay after surgery in an effort to better understand postoperative pain management with biomarkers of worsened postoperative pain.

Study Overview

• Status: Recruiting
• Conditions: Post Operative Pain; Opioid Use, Unspecified

Detailed Description

The objective for this research are:

1. Assess differences in pain reception in patients with existing or previous opioid use disorder versus controls after elective spine surgery via pain questionnaires at multiple time points during the perioperative care.
2. Assess circulating immune signatures and neuropeptides associated with pain signaling before and after surgery in patients with and without OUD using flow cytometry and ELISA of patient serum.
3. Assess molecular signatures of dermal cells and nerve endings patients with and without OUD using spatial transcriptomics on epidermis- and dermis-containing tissue samples from surgical incision.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Ala Nozari, MD PhD; Phone Number: 617-638-6950; Email: ala.nozari@bmc.org
• Study Contact Backup: Name: Xuan He, PhD; Phone Number: 617-638-6950; Email: xuan.he@bmc.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center/Boston University Medical Campus
      • Contact: Ala Nozari, MD PhD; Phone Number: 617-638-6950; Email: ala.nozari@bmc.org
      • Contact: Xuan A He, PhD; Phone Number: 617-638-6950; Email: xuan.he@bmc.org
      • Principal Investigator: Venetia Zachariou, PhD
      • Principal Investigator: Ala Nozari, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with elective spine procedures scheduled involving incision (including laminectomy, discectomy, foraminotomy, scoliosis correction, decompression and fusion) will be divided into four groups: two no opiod use groups and two opioid use groups. The no opioid use groups will consist of two subgroups of participants with no prior pain disorders who have received no long-term opioid prescriptions (n=10), as well as patients with chronic pain disorders who have received no long-term high dose opioid prescriptions (n=10). The opioid use group will consist of two subgroups- participants with OUD (n=10), and participants without OUD, but have been prescribed opioid medication for chronic pain disorders (n=10).

Description

Inclusion Criteria:

Opioid user cohorts:

• Individuals with current OUD as defined by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Individuals requiring ≥20 mg of MME/day medication to manage a chronic pain problem.
• Patients scheduled to undergo elective surgery
• Able to provide informed consent

Control Group Cohorts:

• Individuals who are not taking high dose opioids (≤20 MME/day) nor illicit substances and have no history of opioid use disorder
• Individuals with reported chronic pain not yet taking medication for their pain
• Patients scheduled to undergo elective surgery
• Able to provide informed consent

Exclusion Criteria:

Substance User Cohort:

• Patients with contraindications for elective surgery
• Individuals with no history of opioid use

Control Group Cohort:

• Individuals with a history of opioid use >20 MME/day or illicit substance use
• Patients with contraindications for elective surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Group 1- Patients with Opioid Use Disorder (OUD); Participants in this group will be diagnosed with OUD, defined by cognitive, behavioral, and physiological symptoms indicating using opioids despite significant opioid-related problems.
Group 2- Patients who are engaged in long-term opioid therapy (LTOT) for chronic pain; Participants in this group will be engaged in long-term opioid therapy (LTOT) for chronic pain management under medical supervision, without exhibiting the problematic behaviors or experiencing the significant impairment or distress outlined in the OUD criteria.
Group 3- Patients with chronic pain but no (or minimal) opioid use; Participants in this group will have chronic pain but no (or minimal) opioid use where chronic pain is defined as pain that lasts more than three months or beyond the expected period of healing but opioid use is < 20MME with <3 weeks of duration.
Group 4- Patients without chronic pain; Participants in this group will not suffer from chronic pain but choose to undergo spine surgery due to structural abnormalities or conditions that could potentially lead to pain, neurological issues, or other significant health problems

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific gene expressed	This outcome will be assessed by the transcriptomic profile of dermal tissue from patient excision site using the Visium system to quantify gene expression changes in the dermis. Dermis tissue, about 5mm (length) x 3mm (width) x 2 mm (depth) in size, will be extracted.	The date of scheduled surgery assessed through the study completion, about two years
Type and concentration of inflammatory cells present and selective biomarkers	The inflammatory profile of whole blood such as the quantity and type of circulating immune cells, e.g. complete blood count (CBC) with differential will be assessed using flow cytometry.A blood sample, about 10mL in volume, will be obtained at the preoperative waiting area immediately after IV placement.	The date of scheduled surgery assessed through the study completion, about two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceived pain using a visual pain scale	standard Wong-Baker FACES® Pain Rating Scale of 0-10, 0 being no pain, 10 being worst pain	~2 weeks before surgery; 24, 36, 48, and 72 hours post-surgery before discharge; ~2 weeks after discharge
Perceived pain using the McGill pain scale	The McGill Pain Questionnaire (MPQ) is composed of 78 words. Respondents choose those that best describe their experience of pain.The McGill pain scale descriptors fall into four groups: sensory, affective, evaluative, and miscellaneous. Scores are tabulated by summing values associated with each word; scores range from 0 (no pain) to 78 (severe pain).	~2 weeks before surgery; 24 hours post-surgery before discharge; ~2 weeks after discharge
Anesthesia and pain management method	Anesthesia method will be abstracted from the electronic medical records.	Within 1 week of the surgical visit
Opioid burden	The total amount of analgesics administered will be abstracted from the electronic medical records.	Within 1 week of the surgical visit
Post-operative recovery and complications	Incision site healing status, infection, and any complications will be abstracted from the electronic medical records.	Within 1 week of the surgical visit
Perceived pain during postsurgical recovery using the remote pain survey.	Investigator-developed pain survey that describes the pain level, location, and how it affects quality of life. The survey contains a pain scale from 0 to 10 with 0 being no pain and 10 being worst pain. The survey also contains non-numerical measures describing the location and impact of the pain.	1, 2, 3, 4 week post-discharge

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: Ala Nozari, MD PhD, Boston Medical Center, Anesthesiology

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 7, 2024
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Gene expression; Flow cytometry; Inflammatory profile; Opioid use disorder (OUD); Visium slide sequencing; Sensation pain
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Pain; Neurologic Manifestations; Mental Disorders; Postoperative Complications; Pathologic Processes; Substance-Related Disorders; Chemically-Induced Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Opioid-Related Disorders
• Other Study ID Numbers: H-44193

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No