Propofol-Enhanced Assessment of Ketamine for Chronic Pain and Depression

A numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain) over the past 24 hours will be used to assess pain intensity.

The 16-item Quick Inventory of Depressive Symptomatology Self-Report will be used to assess the severity of depressive symptoms. Items are self-rated on a 4-point scale tailored to each depression-related symptom. Higher total scores indicate greater depression symptom severity.

Blinding will be assessed by asking participants to guess which treatment they received and rate their certainty on a simple 0-100 scale.

Adverse events (AEs) will be assessed through a combination of patient self-report, interviews by study staff, and surveillance of medical records by the research team. AEs will be graded by severity (1=mild, 2=moderate, 3=severe, 4=life threatening, and 5=death) and relatedness to the intervention (0=definitely unrelated, 1=unlikely, 2=possibly related, 3=probably related, 4 definitely related).

The Ketamine Side Effect Tool (KSET) is a standardized questionnaire designed to systematically assess the side effects experienced during or after ketamine administration. It covers a range of potential adverse effects, including dissociative, cardiovascular, and psychotomimetic symptoms. Participants are asked to rate the severity of each adverse effect as 'Never', 'Mild', 'Moderate', or 'Severe'.

Participants will be interviewed by study staff using the modified Brice Questionnaire, a set of questions asked in sequence to determine if the participant remembers anything between the time of induction and their awakening.

Expectations will be measured by asking participants to rate how effective they expect their treatment will be using a visual analog sliding scale from 0 ("Not effective at all") to 100 ("Completely effective"). They will then be asked to rate their level of confidence on a scale from 0 to 100%.

A pressure algometer device applied to the upper trapezius muscle will measure the pressure pain threshold by applying a controlled, gradually increasing force until the participant reports pain.

Mechanical temporal summation will be measured by applying the blunt tip of a thin flexible filament to the back of the hand and the lumbar region. Participants will be asked report pain intensity on a sale from 0 to 100 after a single application and after 10 repeated applications.

Conditioned pain modulation (CPM) measures the ability of the nervous system to inhibit a painful stimulus in the presence of another aversive stimulus. In this study, participants will immerse one hand in cold water and undergo pressure pain threshold measurements in the opposite trapezius muscle before, during, and after immersion.

The CHOIR Body Map is a visual tool that allows individuals to indicate the location(s) of their pain on a human body outline.

The 8-item PROMIS Pain Interference Short Form assesses the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are self-rated on a 5-point scale ranging from 1 ("Not at all") to 5 ("Very Much"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater pain interference.

Participants are asked to rate how their pain medication usage has changed compared to before treatment

The 20-item PROMIS Physical Function Short Form assesses the ability to carry out physical tasks and activities in one's daily life. Items are self-rated on a 5-point scale ranging from 1 ("Unable to do") to 5 ("Without any difficulty"). Raw score totals are converted to standardized T-scores, with a higher T-score representing better physical function.

The 8-item PROMIS Sleep Disturbance Short Form assesses an individual's perception of their sleep quality. Items are self-rated on a 5-point scale ranging from 1 ("Not at all") to 5 ("Very much"). Raw scores are converted to standardized T-scores, with higher a T-score representing more severe sleep disturbance.

The 7-item Generalized Anxiety Disorder (GAD-7) Scale assesses the severity of anxiety symptomsover the past two weeks. Items are self-rated on a 4-point scale ranging from 0 ("Not at all") to 3 ("Nearly every day"), reflecting the frequency of symptoms. Higher total scores indicate greater anxiety symptom severity.

The 7-item Peace of Mind Scale assesses an individual's overall sense of inner calm and contentment. Items are self-rated on a 5-point scale ranging from 1 ("Not at all") to 5 ("All of the time"). Higher total scores reflect a greater sense of peace of mind.

The 10-item Emotion Regulation Questionnaire assesses individual differences in the habitual use of cognitive reappraisal and expressive suppression strategies. Items are self-rated on a 7-point scale ranging from 1 ("Strongly disagree") to 7 ("Strongly agree"). Higher scores on the cognitive reappraisal subscale indicate a greater tendency to reinterpret situations to manage emotions, while higher scores on the expressive suppression subscale indicate a greater tendency to inhibit outward emotional expression.

The 14-item Snaith-Hamilton Pleasure Scale measures an individual's capacity to experience pleasure from various activities over the past 2 weeks, the absence of which indicates anhedonia. Items are self-rated on a 4-point scale ranging from 0 ("Strongly disagree") to 3 ("Strongly agree"). Lower total scores indicate greater degree of anhedonia.

The total number of consented, eligible participants enrolled by the end of the study divided by the amount of time between date of opening enrollment and the date of consent from the last participant.

The proportion of patients who are contacted by study staff for recruitment who provide written informed consent to study procedures.

Participants are asked at the end of the study to rate their experience with study procedures and to provide feedback for improvement.