A randomized trial to examine the mechanisms of cognitive, behavioral and mindfulness-based psychosocial treatments for chronic pain: Study protocol.

This randomized trial will evaluate the mechanisms of three chronic pain treatments: cognitive therapy (CT), mindfulness meditation (MM), and activation skills (AS). We will determine the extent to which late-treatment improvement in primary outcome (pain interference) is predicted by early-treatment changes in cognitive content, cognitive process, and/or activity level. The shared versus specific role of these mechanisms across the three treatments will be evaluated during treatment (Primary Aim), and immediately post-treatment to examine relapse mechanisms (Secondary Aim). We will enroll 300 individuals with chronic pain (with low back pain as a primary or secondary condition), with 240 projected to complete the study. Participants will be randomly assigned to eight, 1.5 h telehealth group sessions of CT, MM, or AS. Mechanisms and outcomes will be assessed twice daily during 2-week baseline, 4-week treatment period, and 4-week post-treatment epoch via random cue-elicited ecological momentary assessment (EMA); activity level will be monitored during these time epochs via daily monitoring with ActiGraph technology. The primary outcome will be measured by the PROMIS 5-item Pain Interference scale. Structural equation modeling (SEM) will be used to test the primary aims. This study is pre-registered on clinicaltrials.gov (Identifier: NCT03687762). This study will determine the temporal sequence of lagged mediation effects to evaluate rates of change in outcome as a function of change in mediators. The findings will provide an empirical basis for enhancing and streamlining psychosocial chronic pain interventions. Further, results will guide future efforts towards optimizing maintenance of gains to effectively reduce relapse risk.

Stimulation-produced analgesia and its cross-tolerance between dorsal and ventral PAG loci.

This study explored the development of tolerance to brain stimulation-produced analgesia in both dorsal and ventral periaqueductal gray (PAG) sites and the development of cross-tolerance between naloxone-reversible and non-reversible sites. Cross-tolerance was produced from non-naloxone-reversible sites to naloxone-reversible sites (NNR-NR) and from naloxone-reversible sites to non-naloxone-reversible sites (NR-NNR). The following conclusions can be drawn from the present study: (1) the descending pain inhibitory systems within the PAG do not operate in isolation of each other since cross-tolerance to chronic stimulation can be produced between systems; (2) the interaction between the two systems is apparently bi-directional in that cross-tolerance was produced from naloxone-reversible to non-reversible sites and vice versa; and (3) the interaction may be the result of a co-activation of opioid and non-opioid systems produced by electrical stimulation or by a co-utilization of a common neuronal substrate. It is speculated that serotonin is a neurotransmitter involved in the mechanism of convergence.