Protocol for the impact of CBT-I and tapered withdrawal from opioids on pain and opioid use: A randomized controlled trial

INTRODUCTION: Individuals with chronic pain experience comorbid insomnia, heightened arousal, and abnormal pain-related brain activation. Although opioid therapy is commonly prescribed for widespread pain, it offers questionable long-term benefit and is associated with arrhythmias, overdose, and death. The Cognitive Activation Theory of Stress (CATS) suggests poor sleep and arousal lead to critical changes in brain activation that increase pain severity and lead to opioid use. Cognitive Behavioral Therapy for Insomnia (CBT-I) improves sleep and holds promise for improving arousal, abnormal brain activation, and pain in individuals with comorbid chronic pain and insomnia, but does not reduce opioid use. Because CBT-I improves each mediator hypothesized to contribute to opioid use, it warrants evaluation as a neoadjuvant to opioid tapering. This trial tests whether improving sleep and decreasing arousal can normalize brain activation and decrease pain prior to gradual opioid tapering, facilitating reduced opioid use. METHODS & ANALYSIS: 165 adults with comorbid chronic widespread pain and chronic insomnia who use prescription opioids will be recruited from Tampa, Florida, and surrounding areas, and randomized to CBT-I or Sleep Hygiene and Related Education (SHARE). Following intervention, they will undergo gradual opioid tapering. Two booster sessions will be administered after intervention and withdrawal, but before the 6-month follow-up. Compared with SHARE, CBT‑I is expected to improve insomnia severity, reduce physiological and subjective arousal, reduce pain intensity, and normalize pain‑related brain activation (i.e. reduced BOLD responses to painful stimuli in the Right Insula, Left Inferior Frontal Gyrus, and Right Lentiform Nucleus) and altered functional connectivity, at post‑treatment and 6‑ month follow‑up.