Impact of Gut Microbiota and Tryptophan Metabolites on Acute Pain in Lumbar Disc Herniation Surgery Patients

The Impact of Microbiota and Associated Blood Tryptophan Metabolites on Pain Perception in Patients Undergoing Lumbar Disc Herniation Surgery

It is well-established that the gut microbiota plays a crucial role in various pain mechanisms, including visceral pain, inflammatory pain, headache, neuropathic pain, and opioid tolerance. Changes in the gut microbiome can alter pain perception. In our study, The investigator investigated the effects of microbiota alterations and the associated tryptophan metabolites on acute pain using the Visual Analog Scale (VAS).

Study Overview

• Status: Completed
• Conditions: Postoperative Pain, Acute; Microbial Substitution; Tryptophan Metabolism Alterations
• Intervention / Treatment: Procedure: Pain Perception in Patients Undergoing Lumbar Disc Herniation Surgery

Detailed Description

The study included patients aged 18 and above undergoing lumbar disc herniation surgery. Blood samples were collected preoperatively, at 8 hours, and at 24 hours postoperatively to analyze tryptophan metabolites (picolinic acid, 3- Hydroxykynurenine, anthranilic acid, kynurenine, quinolinic acid, kynurenic acid, xanthurenic acid). Concurrent VAS pain assessments were conducted, and correlations between tryptophan metabolites and VAS were evaluated.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• Turkey
  • Balçova
    • İzmir, Balçova, Turkey, 35100
      • Yunu Çelik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Our study includes 37 lumbar disc herniation (LDH) surgeries performed in Dokuz Eylül University Faculty of Medicine Central Operating Rooms Brain and Nerve Surgery Hall. For the blood samples in which the investigators evaluated tryptophan metabolites; 2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed.

Concurrently with each blood draw, the patient's VAS score, the nature of the pain, and vital signs were recorded. Patient records, clinical histories, examination findings, and relevant laboratory results were electronically recorded.

Description

Inclusion Criteria:

• Patients undergoing lumbar disc herniation surgery at Dokuz Eylül University Hospital.
• Patients who have read and consented to the informed consent form for the study.
• Age 18 years or older.
• Surgery duration exceeding 2 hours.

Exclusion Criteria:

• Patients are unwilling to participate in the study.
• Surgery duration less than 2 hours.
• Patients under the age of 18.
• Patients with a history of abdominal surgery.
• Patients who received antibiotic therapy for intestinal pathology within the last 3 weeks.
• Patients with known abdominal pathologies suspected to alter the microbial flora (e.g., Crohn's disease, ulcerative colitis, celiac disease).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tryptophan metabolites (Picolinic Acid)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between picolinic acid and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the picolinic acid levels (ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (3-Hydroxykynurenine)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between 3-Hydroxykynurenine and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the 3-Hydroxykynurenine levels(ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (Anthranilic Acid)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between anthranilic acid and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. The relevant laboratory team measured the anthranilic acid levels (ng/mL) following the required centrifugation procedures.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (Kynurenine)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between kynurenine and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the kynurenine levels (ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (Quinolinic Acid)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between quinolinic acid and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the quinolinic acid levels (ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (Kynurenic Acid)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between kynurenic acid and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the kynurenic acid levels (ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Tryptophan metabolites (Xanthurenic Acid)	2 mL of blood was used from the blood samples taken during routine surgery preparation for the patients and from the routine blood samples taken in the postoperative period, and no additional invasive intervention was performed. The investigator elucidated the relationship between xanthurenic acid and its variations due to microbiota alterations with VAS in acute pain. Preoperative, postoperative, 8th-hour, and 24th-hour blood samples were routinely collected from patients, with 2 mL of sample material used each time. After the necessary centrifugation processes, the relevant laboratory team analyzed the xanthurenic acid levels (ng/mL).	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Visual Analog Scale	In VAS assessment, patients are typically asked to choose a value between "0, no pain" and "10, the worst imaginable pain." VAS is an 11-point scale (ranging from 0 to 10) that allows patients to numerically express the intensity of their pain. Blood samples were planned and collected from patients during the preoperative evaluation, at the 8th postoperative hour, and at the 24th postoperative hour, adhering to clinical routines for these procedures. Concurrently with each blood draw, the patient's VAS score, the nature of the pain, and vital signs were recorded.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure (mmHg)	The study measured the systolic blood pressure (mmHg) of patients at specified time points.The patients' systolic blood pressure data were recorded simultaneously with the blood samples taken during routine surgery preparation and at the 8th and 24th hours postoperatively.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Diastolic Blood Pressure (mmHg)	The study measured the diastolic blood pressure (mmHg) of patients at specified time points.The patients' diastolic blood pressure data were recorded simultaneously with the blood samples taken during routine surgery preparation and at the 8th and 24th hours postoperatively.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Pulse Rate (beats per minute)	The study measured patients' pulse rate (beats per minute) at specified time points.The patients' pulse data were recorded simultaneously with the blood samples taken during routine surgery preparation and at the 8th and 24th hours postoperatively.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Respiratory Rate (breaths per minute)	The study measured the respiratory rate (breaths per minute) of patients at specified time points. The patients' respiratory rate data were recorded simultaneously with the blood samples taken during routine surgery preparation and at the 8th and 24th hours postoperatively.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Oxygen Saturation (%)	The study measured patients' oxygen saturation (%) at specified time points.The patients' oxygen saturation data were recorded simultaneously with the blood samples taken during routine surgery preparation and at the 8th and 24th hours postoperatively.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Nature of Postoperative Pain Assessed by the McGill Pain Questionnaire (MPQ)	The McGill Pain Questionnaire (MPQ) was used to evaluate and categorize the nature of pain. The study assessed the nature and quality of acute postoperative pain using the McGill Pain Questionnaire (MPQ) at specified time points. Although all of the patients' pain was acute postoperative pain, the pain qualities were recorded simultaneously, taking into account the differences in pain qualities. The MPQ was used to evaluate and categorize the nature of pain. The MPQ includes descriptors of pain which are categorized into sensory, affective, evaluative, and miscellaneous dimensions. Each descriptor is rated on an intensity scale of 0 (none) to 3 (severe), and scores are summed to provide an overall pain score. Higher scores indicate worse pain.	Preoperative: Before surgery; Postoperative 8th-hour: 8 hours after surgery;Postoperative 24th-hour: 24 hours after surgery
Comorbidity Assessment in Relation to Pain and Tryptophan Metabolites	The study recorded patients' comorbidities, specifically those identified during the preoperative anamnesis process, and evaluated their potential impact on the nature of pain and tryptophan metabolites. Comorbidities identified as exclusion criteria, particularly those believed to affect intestinal microbiota and related to abdominal conditions, were also considered. Patients' comorbidities identified during the preoperative anamnesis process were meticulously documented to assess their influence on pain characteristics and tryptophan metabolites. Additionally, comorbidities identified as exclusion criteria due to their potential to alter intestinal microbiota and their association with abdominal conditions were thoroughly evaluated.	Preoperative anamnesis process: Prior to surgery, during patient assessment, Follow-up: Through study completion, an average of 1 year
Anesthesia induction drugs	Although standardization of drugs used in anesthesia is difficult, standardization of induction drugs was partially achieved because the investigators chose a single surgery group. The investigators recorded all of this data during anesthesia applications.	During anesthesia procedure
Anesthesia duration and surgery times	Our study detailedly recorded the duration of anesthesia and surgery. To ensure a certain level of standardization, we included only lumbar disc surgery, which is considered sterile. Additionally, surgeries shorter than a specified duration were excluded as they might not provide significant metabolic changes. These durations were carefully recorded throughout the entire surgery and anesthesia period. The investigators accepted these durations as one of the elimination criteria due to their potential impact on pain and physiological mechanisms.	During surgery
Age of Investigator	The investigator's age was recorded during the preoperative anamnesis process to understand its influence on the study variables.	Preoperative: During the preoperative anamnesis process
Weight of Investigator	The weight of the investigator was recorded during the preoperative anesthesia process to understand its influence on the study variables.	Preoperative: During the preoperative anamnesis process
Height of Investigator	The height of the investigator was recorded during the preoperative anamnesis process to understand its influence on the study variables.	Preoperative: During the preoperative anamnesis process
Body Mass Index (BMI) of Investigator	The Body Mass Index (BMI) of the investigator was calculated from recorded height (in meters) and weight (in kilograms) during the preoperative anamnesis process to understand its influence on the study variables.BMI values are reported in units of kg/m².	Preoperative: During the preoperative anamnesis process
Gender of Investigator	The gender of the investigator was recorded during the preoperative anamnesis process to understand its influence on the study variables.	Preoperative: During the preoperative anamnesis process

Collaborators and Investigators

• Sponsor: Dokuz Eylul University
• Investigators: Study Chair: Yunus Celik, M.D., Dokuz Eylül University Hospital, Faculty of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Actual): November 24, 2022
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Microbiota; Acute Pain; Tryptophan; Picolinic Acid; Kynurenic Acid; Xanthurenic Acid; Quinolinic Acid
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Pathological Conditions, Anatomical; Spinal Diseases; Bone Diseases; Hernia; Pain, Postoperative; Intervertebral Disc Displacement; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; Tryptophan
• Other Study ID Numbers: DEU-Çelik001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigators do not see any harm in sharing the data of our study to contribute to other studies and meta-analyses. The investigators received our informed consent, but the investigators made such a choice because the investigators doubted that it would be public.

Drug and device information, study documents

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