Chronic Widespread Pain and White Blood Cell Activation

"Since beginning treatment, how would you describe the change (if any) in ACTIVITY LIMITATIONS, SYMPTOMS, EMOTIONS and OVERALL QUALITY OF LIFE related to your painful condition?" (CHOOSE ONE).

• No change (or condition has got worse)
• Almost the same, hardly any change at all
• A little better, but not noticeable change at all
• Somewhat better, but the change has not made any real difference
• Moderately better, and a slight but noticeable change
• Better, and a definite improvement that has made a real and worthwhile difference
• A great deal better, and a considerable improvement that has made all the difference

Patients scoring either 6 or 7 on the PGIC scale are categorized as "improved". Patients scoring either 6 or 7 on the PGIC scale are categorized as "improved". We will use this definition as a dichotomous variable.

we will use a 0 to 10 numerical ranking scale adapted to RedCap to collect pain intensity ratings. In this scale, '0' means 'no pain at all' and '10' means 'the worst intense pain imaginable'. At baseline, weeks 4, 8, 12 and 16 clinical visits, patients will be asked by the research team to rate their lowest, average, and highest pain intensity for the previous day.

Intensity of the lowest, average, and highest pain at 'week 16' will be on of the secondary end points of the study.

We are also interested in the proportion of patients that show a 50% reduction in their pain intensity after 16 weeks of treatment with KF. Thus, we will assess this proportion also for the lowest, average, and highest pain intensity.

As patients rate their lowest, average, and highest pain intensity daily on RedCap, they will be prompted to indicate also for how many hours each of these pains lasted. The product of pain intensity by pain duration (in hours) will generate the pain index (Example: pain intensity of 9 with a duration of 6 hours = pain index 54)

Pressure pain thresholds (PPT) will be determined using a digital pressure algometer with a flat round transducer, applied bilaterally at the trapezius muscle and lateral epicondyle. Pressure will be increased at a steady rate of approximately 1 kg/s until the subject indicates that the pressure sensation is perceived as painful sensation (threshold), and the pressure in kg recorded. The first trial at each test site will be considered a practice trial, and will be excluded from data analysis. In subsequent trials, the pressure level at the time the subject indicates to first perceive the pressure sensation to become a painful sensation will be recorded as the threshold estimate. If no response is given at the point the algometer reaches maximum pressure, the maximum value will be used as the threshold value. This procedure will be repeated three times at each test site, and the mean value will be recorded as the subjects threshold.

The scale can be completed in person, by mail, or by phone. Scoring: item scores range from 0-4. The total FDI score is a sum of all of the items and can be easily hand scored. Scores range from 0-60, with higher scores indicating greater functional disability. (no/minimal disability 0 -12, moderate disability 13-29, and severe disability >30)

): is a 47-item scale intended to assess children's report of symptoms corresponding to selected DSM-IV anxiety disorders and depression. The RCADS is a 47-item scale with subscales including: separation anxiety disorder (SAD), social phobia (SP), generalized anxiety disorder (GAD), panic disorder (PD), obsessive compulsive disorder (OCD), and major depressive disorder (MDD). It also yields a Total Anxiety Scale (sum of the 5 anxiety subscales) and a Total Internalizing Scale (sum of all 6 subscales). Recall period for item: one week. Scoring programs are available at www.childfirst.ucla.edu/resources for scoring the RCADS.

Pittsburgh Sleep Quality Index (PSQI): 19 items scale assessing sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. Recall period for item: one month Scoring: Point values of each item in of the seven subscales are summed and then combined as indicated to generate a subscale score. These totals are summed to create the global PSQI score.

Patients will be asked at each evaluation to quantify the number of days lost because of pain and/or associated symptoms in the previous four weeks. Days of school missed because of medical appointments will not be quantified for the role functioning analysis.

Patients will be allowed to reduce the doses or, eventually, to stop the use analgesic medication under medical supervision if there is a significant reduction in pain intensity (50% reduction in pain intensity rating) or in the associated symptoms

We will use an electronic list of adverse reactions to check for treatment-emergent adverse events. This list was created by us to run on RedCap, based on the list of adverse reactions reported by patients participating in a double-blind, placebo controlled Canadian Multicentre Trial (196 asthmatic children aged 5- 17 years) (Rackham, A. et al. A Canadian multicenter study with Zaditen (ketotifen) in the treatment of bronchial asthma in children aged 5 to 17 years. The Journal of allergy and clinical immunology 84, 286-296 (1989).

RNA expression patterns will be compared before and after treatment,