Phenomics and Genomics of Clinically Relevant Chronic Postsurgical Pain

Measured using the numeric rating scale (0=no pain; 10=worst pain imaginable)

The SF-MPQ-2 is a 22-item, expanded and revised version of the SF-MPQ designed to measure the qualities of neuropathic and non-neuropathic pain. Exploratory and confirmatory factor analyses revealed the presence of the following four factors or subscales: (1) continuous pain, (2) intermittent pain, (3) neuropathic pain, and (4) affective pain descriptor.

The S-LANSS is a validated 7-item questionnaire designed to distinguish whether pain is predominately neuropathic or nociceptive in origin.

The ASI-3 is a revised version of the widely used, 16-item scale ASI that measures concerns that anxiety and anxiety-related symptoms will lead to harmful negative consequences. Each item is rated on a 5-point scale ranging from very little (0) to very much (4).

The PCS consists of 13 items describing thoughts and feelings that individuals may experience when they are in pain. Each item is rated on a 5-point scale ranging from not at all (0) to all the time (4).

The PASS-20 is a shortened 20-item version of the original Pain Anxiety Symptoms Scale designed to measure fear and anxiety responses specific to pain, including avoidance. The PASS-20 has four 5-item subscales, including (1) cognitive anxiety, (2) escape and avoidance, (3) fearful thinking, and (4) physiological anxiety.

The PDI assesses the extent to which persistent pain interferes with an individual's ability to engage in seven different areas of everyday activity including: (1) family/home responsibilities, (2) recreation, (3) social activity, (4) occupation, (5) sexual behavior, (6) self-care, and (7) life-support activity.

The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) is a 17-item self-report measure based on the current DSM-IV symptoms for PTSD. Respondents are asked to indicate how much they have been bothered by each symptom 5-point scale ranging from not at all (1) to extremely (5).

The HADS is the most widely used scale for measuring symptoms of anxiety and depression among medical inpatients, outpatients and the general population and consists of 7 anxiety and 7 depression-related items.

The SCL-90-R is a widely-used self-report symptom inventory measuring psychological symptoms of psychiatric and medical patients. Participants rate each item on a five-point scale of distress, ranging from 0 (no distress) to 4 (extreme distress).

The CPAQ is a 20-item questionnaire that measures how participants react and adapt to living with chronic pain. Participants respond to "how true" each item is by selecting a number from 0 ("never true") to 6 ("always true").

The MAAS is a 15-item scale designed to measure a central feature of dispositional mindfulness characterized by "open or receptive awareness of and attention to" the present. Participants respond to how frequently/infrequently they experience each item by selecting one of six response options on a Likert rating scale ranging from 1 ("Almost always") to 6 ("Almost never").

The PSEQ is a 10-item Likert-type questionnaire, designed specifically for chronic pain, where patients are asked to rate their confidence to complete certain activities despite pain.

The SPTS is a 12-item questionnaire that was designed to measure the anxiety-related cognitive, emotional and behavioural reactions to pain that resemble symptoms of a traumatic stress reaction. Each item is rated on a 5-item Likert scale (from 1 (not at all true) to 5 (entirely true)).

This is a general questionnaire that asks its questions providing responses in units of days.

The PSQI questionnaire is much more specific, identifying specific responses and reasons why patients may be having trouble sleeping such as: (1) cannot get to sleep within 30 minutes and (2) wake up in the middle of the night or early morning.

The Actiwatch-64 is a small wrist watch-like device that contains an accelerometer that records limb movements and has a memory storage capacity for up to 11 days109. The Actiwatch-64 provides a non-invasive method of collecting activity data around the clock. Activity data are downloaded to a laptop and standard sleep parameters such as latency to sleep (SOL), wake time after sleep onset (WASO), and total sleep time (TST) are inferred by software based on the presence and absence of limb movements during specified time intervals. Total activity during periods scored as not sleep is also available.

Each morning after surgery, up to and including the morning of discharge home from the hospital, a Sleep Diary will be completed.

Pain thresholds in response to mechanical pressure applied to the skin will be obtained using a Pressure Algometer.

Thermal stimuli will be delivered using the Medoc Thermal NeuroSensory Analyzer

Participants will be required to place their right hand on four plates, two of which will be pre-cooled to 10˚C and 20˚C and two preheated to 40˚C and 50˚C. Participants will alternate between these stimuli and a grill of mixed 20˚C and 40˚C interlaced bars with 5sec intervals between applications.

This simple test robustly activates the sympathetic system, which aggravates neuropathic pain in some chronic pain patients. Participants will be asked to rest supine on a couch and relax with eyes closed, and to take the deepest possible inspiration and then breathe normally. Three ratings of ongoing spontaneous pain will be taken at 1, 2, and 5 min after expiration. Two baseline blood pressure (systolic, diastolic and mean arterial pressure) and pulse rate measurements will be taken just before the Gasp Test and at 1 and 2 min thereafter, just after the pain ratings. Cardiovascular parameters will be carried out using an automated blood pressure cuff.

The participant will immerse their right hand (above the elbow) in ice cold water and keep it there until they cannot tolerate the pain. The pain tolerance threshold will be recorded with a stopwatch, as the time to withdrawal; cut-off at 3 min. They will then use the NRS (0-100) to rate the magnitude of pain and unpleasantness.

A genome-wide exomic sequencing and full genome sequencing will be carried out in search of a common and rare variants that predispose carriers to acute post-surgical pain and the transition to pain chronicity post-surgery.