The Effects of Minocycline in Opioid-maintained Patients

The Cold Pressor Test (CPT) measures pain threshold (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report the first time they experience pain (pain threshold). Lower scores indicate lower pain threshold. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

The Cold Pressor Test (CPT) measures pain threshold and pain tolerance (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report when the pain becomes unbearable (pain tolerance). Lower scores indicate lower pain tolerance. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

Brief Pain Inventory - Short Form: BPI-SF is a self-report questionnaire that assesses the impact of pain on daily function, location of pain, pain medications, and amount of pain relief in the past 24 hours or the past week. Each question is scored 0-10, and the scores are summed and then averaged to create a pain severity score. Minimum score is 0; maximum score is 10. Higher scores indicate more severely perceived pain.

Brief Pain Inventory - Short Form: BPI-SF is a self-report questionnaire that assesses 7 questions each rated on a scale of 0-10, which are added and divided by 7. This average score of 7 questions gives a "pain interference with living" score, with a minimum score of 0 and a maximum score of 10.

Higher scores indicate that pain interferes more with aspects of daily life.

For safety reasons, withdrawal signs and symptoms were assessed using a 22-item withdrawal instrument that has been reliably used to assess opiate withdrawal. As an additional assessment of daily pain, the presence of "back pain" item was analyzed. This item has a minimum score of 0 and maximum score of 4, with higher scores indicates more agreement with statement/more back pain.

The POMS is a 65-item scale that divides items amongst eight mood states (tension, depression, anger, fatigue, confusion, vigor) on a 5-point rating scale (0=not at all to 5=extremely). We analyzed the 15-item "Depression" subscale, which has a minimum score of 0 and a maximum score of 75. Higher score indicate more agreement with the statement/more feelings of depression.

The POMS is a 65-item scale that divides items amongst eight mood states (tension, depression, anger, fatigue, confusion, vigor) on a 5-point rating scale (0=not at all to 5=extremely). Total Mood Disturbance is calculated by adding the "tension, depression, anger, fatigue, and confusion" subscale scores and subtracting the "vigor" subscale score. This has a minimum of 0 and a maximum score of 210. Higher score indicate more mood disturbance.

This measure is a subscale of the SF-MPQ, comprised of 11 of the 15 total items. The measure is completed immediately after the CPT, where participants describe their experience of CPT pain by choosing among a series of possible answers [none (score=0), mild (score=1), moderate (score=2), or severe (score=3)]. The items to describe the pain are 'Throbbing','Shooting', 'Stabbing', 'Sharp', 'Cramping', 'Gnawing', 'Hot/burning', 'Aching', 'Heavy', 'Tender', and 'Splitting'. The scores for these 11 items are summed as a measure of Sensory pain, with a minimum score of 0 and a maximum score of 33.

This measure is a subscale of the SF-MPQ, comprised of 4 of the 15 total items. The measure is completed immediately after the CPT, where participants describe their experience of CPT pain by choosing among a series of possible answers [none (score=0), mild (score=1), moderate (score=2), or severe (score=3)]. The items to describe the pain are 'Tiring-Exhausting', 'Sickening', 'Fearful', 'Punishing-Cruel'. The scores for these 4 items are summed as a measure of Affective pain, with a minimum score of 0 and a maximum score of 12.

Serum cytokine analysis assayed using electrochemiluminescence multi-array technology (Meso Scale Discovery, Gaithersburg, MD). IL-1β is measured in pictograms per milliliter (pg/ml). Cytokines were assessed at screening (approximately 1 week prior to medication), and on the last day of medication treatment. Higher numbers indicate higher blood levels of this cytokine.

Serum cytokine analysis assayed using electrochemiluminescence multi-array technology (Meso Scale Discovery, Gaithersburg, MD). IL-6 is measured in pictograms per milliliter (pg/ml).Cytokines were assessed at screening (approximately 1 week prior to medication), and on the last day of medication treatment. Higher numbers indicate higher blood levels of this cytokine.

Serum cytokine analysis assayed using electrochemiluminescence multi-array technology (Meso Scale Discovery, Gaithersburg, MD). TNF-α is measured in pictograms per milliliter (pg/ml).Cytokines were assessed at screening (approximately 1 week prior to medication), and on the last day of medication treatment. Higher numbers indicate higher blood levels of this cytokine.

Participants will be asked "Do you feel any pain at this moment" on seven-point Likert scales (1=strongly disagree to 7=strongly agree) 4 times per day outside of the laboratory (in their natural environment) using a personal digital assistant on days 8-14 of medication treatment. All scores were averaged to compute one score. Higher scores indicate more feelings of pain.

Participants will be asked "Are you craving heroin at this moment" on seven-point Likert scales (1=strongly disagree to 7=strongly agree) 4 times per day outside of the laboratory (in their natural environment) using a personal digital assistant on days 8-14 of medication treatment. All scores were averaged to compute one score. Higher scores indicate more craving for heroin.

Self-report opioid withdrawal scale. Withdrawal symptoms are measured on a 7-point Likert scale (1=strongly disagree, 7=strongly agree). Participants complete these ratings 4 times per day on days 8-14 of medication treatment. All scores were averaged to compute one score. Higher scores indicate more withdrawal symptoms.

The DSST is a test of psychomotor performance, which measures motor persistence, sustained attention, response speed and visuomotor coordination. The task is to fill in blank spaces with the symbols that are paired with the number above the blank space as fast as possible for 90 sec. The minimum score is 0 and the maximum score is 120. Higher numbers indicate better cognitive performance.

The SART is a Go No-Go task. It assesses the ability to withhold responses to an infrequently occurring target (No-Go trials). A total of 225 single digits (25 x 9 digits) are presented on a computer monitor for 250 ms each, immediately followed by a mask for 900 ms. Subjects must press a spacebar in response to every digit except the "3". Higher numbers indicate more errors of commission.

The SART is a Go No-Go task. It assesses the ability to withhold responses to an infrequently occurring target (No-Go trials).The SART is a Go No-Go task. It assesses the ability to withhold responses to an infrequently occurring target (No-Go trials). A total of 225 single digits (25 x 9 digits) are presented on a computer monitor for 250 ms each, immediately followed by a mask for 900 ms. Subjects must press a spacebar in response to every digit except the "3". Higher numbers indicate more errors of omission.