Chronic low back pain (CLBP) afflicts up to 50 million US adults and is a primary cause of disability. Currently, opioid analgesics are a cornerstone of pain management, and are among the most common medications prescribed by physicians for CLBP. Despite their potential benefits, major concerns have been raised regarding opioids due to their potential iatrogenic consequences, such as the development of opioid-induced hyperalgesia (OIH) and prescription opioid misuse (POM), both of which have the potential to impair treatment benefits. It is clear that not all patients taking long-term opioids will experiene these maladaptive effects. Our preliminary data indicate that specific subgroups of pain patients might be more prone to developing OIH, as well as deleterious shifts in central nervous system (CNS) pain-modulatory processes. Furthermore, our preliminary data suggest that OIH and opioid-induced changes in pain modulation might increase patients' propensity to misuse opioids. Given the current opioid prescribing rates in the U.S., there is an urgent need to better understand effects of opioids on CNS pain processing and, in turn, the effects of those sensory changes on risk for opioid misuse or addiction. In this study, we propose to conduct a 4-month randomized, controlled trial of oral opioids among patients with CLBP. In this trial, each participant will undergo quantitative sensory testing (QST) at baseline, before being randomized to receive either extended-release oral morphine or matched placebo. Patients will then undergo repeat QST at 1, 2, 3, and 4 months. At each of these follow-up time points, we will assess changes in pain sensitivity and modulation, and prescription opioid misuse. Treatment efficacy will be assessed using daily electronic dairy entries We hypothesize that an identifiable subgroup of patients, characterized by high levels of negative affect and pain catastrophizing, will be at the greatest risk for experiencing maladaptive opioid-induced changes in pain sensitivity (i.e., OIH) and pain modulation, as well as an increased likelihood of prescription opioid misuse. Collectively, there is a very strong animal literature on OIH (which seems to be a highly robust phenomenon in rats), but there is currently a paucity of prospective human data. We hope that findings from this research would be novel, timely, and would have direct implications for the field of opioid pain management. Identifying subgroups of patients who are at elevated risk for OIH and POM should facilitate more effective tailoring of treatment regimens to individual patients, and aid in reducing the potentially severe iatrogenic impacts of long-term opioid therapy in patients with chronic pain.
The prescription of opioids for the treatment of chronic pain has increased exponentially over the past several decades. While opioids remain a first-line treatment for many acute pain conditions, major concerns have arisen regarding their long-term effects. In the proposed project, we will examine whether specific subgroups of chronic pain patients prescribed opioids are more vulnerable to the potential deleterious effects of opioids, such as opioid-induced hyperalgesia. We will also examine whether those changes in pain sensitivity are associated with the subsequent development of opioid misuse behaviors. This study will have substantial implications for understanding who is at risk for adverse outcomes of long-term opioid treatment.
|Martel, Marc O; Petersen, Kristian; Cornelius, Marise et al. (2018) Endogenous Pain Modulation Profiles Among Individuals With Chronic Pain: Relation to Opioid Use. J Pain :|
|Carriere, Junie S; Martel, Marc Olivier; Meints, Samantha M et al. (2018) What do you expect? Catastrophizing mediates associations between expectancies and pain-facilitatory processes. Eur J Pain :|
|Tompkins, D Andrew; Johnson, Patrick S; Smith, Michael T et al. (2016) Temporal preference in individuals reporting chronic pain: discounting of delayed pain-related and monetary outcomes. Pain 157:1724-32|
|Martel, Marc O; Finan, Patrick H; McHugh, R Kathryn et al. (2016) Day-to-day pain symptoms are only weakly associated with opioid craving among patients with chronic pain prescribed opioid therapy. Drug Alcohol Depend 162:130-6|
|Edwards, Robert R; Dworkin, Robert H; Sullivan, Mark D et al. (2016) The Role of Psychosocial Processes in the Development and Maintenance of Chronic Pain. J Pain 17:T70-92|
|Tsui, Judith I; Lira, Marlene C; Cheng, Debbie M et al. (2016) Chronic pain, craving, and illicit opioid use among patients receiving opioid agonist therapy. Drug Alcohol Depend 166:26-31|
|Edwards, R R; Dolman, A J; Michna, E et al. (2016) Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect. Pain Med 17:1882-1891|
|McHugh, R Kathryn; Weiss, Roger D; Cornelius, Marise et al. (2016) Distress Intolerance and Prescription Opioid Misuse Among Patients With Chronic Pain. J Pain 17:806-14|