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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.
The objective for this research are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
| 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 |
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Inclusion Criteria:
Opioid user cohorts:
Control Group Cohorts:
Exclusion Criteria:
Substance User Cohort:
Control Group Cohort:
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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).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ala Nozari, MD PhD | Contact | 617-638-6950 | ala.nozari@bmc.org | |
| Xuan He, PhD | Contact | 617-638-6950 | xuan.he@bmc.org |
| Name | Affiliation | Role |
|---|---|---|
| Ala Nozari, MD PhD | Boston Medical Center, Anesthesiology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston Medical Center/Boston University Medical Campus | Recruiting | Boston | Massachusetts | 02118 | United States |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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A 10 ml blood sample will be collected for serum analysis immediately before, during, and 24 hours after the surgical procedure. During the procedure, A 5mm (length) x 3mm (width) x 2 mm (depth) tissue sample from the incision site will be collected for later spatial transcriptomic analysis.
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 |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |