Pain Catastrophizing as a Cause for Systemic Inflammation

A main goal of the study is to better understand pain mechanics. Research has linked pro-inflammatory cytokines to the development and progression of pain. Research has also linked female gender with increases in pro-inflammatory cytokines (relative to males) following psychological stress. Therefore, we hypothesize that women in the study who evidence significantly increased pro-inflammatory cytokines following pain catastrophizing may be at risk for the progression of their pain condition.

The sample will be 60 women having chronic musculoskeletal pain (we will enroll up to 75 persons to account for attrition and screen failures but require the usable data of only 60 women). Based on enrollment rates for our previous study, and given our expanded catchment area, we expect to enroll 60 persons within approximately 14 months and to complete the experimental phase of the study within approximately 17 months. The follow-up phase of the study will continue, for as long as participants agree to be followed for up to 10 years.

The study design is a randomized, controlled experiment. Participants are consented and enrolled under the impression that they will undergo one stress experiment day (lasting about 5.5 hours). However, on their study day we will randomize subjects to either be in the control group or the catastrophizing (stress) group.

Screening Visit: The purpose of this visit is to determine eligibility and obtain informed consent. Inclusion and exclusion criteria will be assessed through medical record review, a screening interview, and a hormonal bloodspot kit. A questionnaire will also be given to determine level of depressive symptoms and to assess for suicidality. The hormonal bloodspot kit involves a finger prick and obtaining about 5-6 drops of blood. If lab analysis of this kit determines abnormal hormonal levels, persons will be excluded from further participation in the study. Participants will be given a saliva kit to gather 4 saliva samples at home over the course of one day. Participants will store these saliva samples in their refrigerator. They will either bring in the kit at the time of their study visit or mail the kit in a prepaid box given to them (the hormones in the saliva are shelf stable for up to 3 weeks; we will ask participants to refrigerate the samples if they are not immediately mailing them or bringing them to the study site. In this way we will best ensure that samples will be preserved and usable). All participants enrolled in the study will be under the impression that they will be participating in a catastrophizing experiment during their study day. However, only half of the participants will actually experience the 10-minute stress experiment on experiment day. We have included this minor form of deceit in the protocol so we can control for the anticipatory stress of expecting to experience a negative emotional experiment. We highlight here that the mild deception will occur for only half the sample (those going into the control group) and it represents a decrease in risk for these persons.

Study Visit: This study visit is scheduled to occur during the follicular phase of the menstrual cycle (this phase follows the menstrual period and is easy to predict in our sample of normally menstruating women by using a calendar). If difficulty is encountered in predicting the date of the follicular phase, participants will call the PI or study coordinator when their menstrual period begins to schedule their study date (approximately 5-6 days from onset on menses). All participants arrive in a fasting state, during their follicular phase to control for sex-steroid influences on immunity. 3ml of blood will be drawn for hormone levels. The hormone level will not be analyzed at this time, but saved until the end of the study for analysis, if needed. A complete cardiometabolic panel will be measured via bloodspot. If the subject agrees to take part in the sub study, we will take an additional 10mL of blood for an extra bloodspot card that we will store for future pain/genomic research. Pain ratings will be assessed, and questionnaires will be completed. Standardized meals (with no caffeine) will be served to participants (breakfast, lunch, snacks). An OCTRI research nurse will place an intravenous catheter into the arm of participant's choosing. A Holter heart monitor will be placed on participants by nursing. This is a portable device that measures heart beat. Placement of the leads around the heart involves cleaning the skin. The monitor will remain affixed for the duration of the study visit. At this point participants will be randomized to either be in the control group or in the catastrophizing group using a random number generator. After they are randomized into one of the two groups, the deception will be revealed to the control group, and its rationale explained. Those randomized to the stress group will be informed of the deception, and the rationale for having used it, at the conclusion of the study visit .