Psychology

The purpose of this study is to evaluate the effectiveness of a multimodal approach to treating chronic low back pain.

Therapeutic interventions for neuropathic pain (NP), such as the NMDA-antagonist ketamine, can vary widely in effectiveness; Here, we conducted a longitudinal functional MRI study to test the hypothesis that the pain relieving effect of ketamine is due to reversal of abnormalities in regional low frequency brain oscillations (LFOs) and abnormal cross-network functional connectivity (FC) of the dynamic pain connectome. We found that: 1) ketamine decreased regional LFOs in the posterior cingulate cortex (PCC) of the default mode network (DMN), 2) a machine learning algorithm demonstrated that treatment-induced brain changes could be used to make generalizable inferences about pain relief, 3) treatment responders exhibited a significant decrease in cross-network static FC between the PCC and regions of the sensorimotor (SM) and salience networks following treatment, 4) the degree of reduced cross-network FC was correlated with the amount of pain relief, and 5) ketamine treatment did not produce significant differences in static or dynamic FC within the ascending nociceptive- or descending antinociceptive pathway. These findings support the proposition that regional LFOs contribute to cross-network connectivity that underlie the effectiveness of ketamine to produce significant relief of neuropathic pain. Together with our recent findings that pre-treatment dynamic FC of the descending antinociceptive pathway can predict ketamine treatment outcomes, these new findings indicate that pain relief from ketamine arises from a combination of a strong and flexible pre-treatment FC of the descending antinocieptive pathway together with plasticity (reduction) of cross-network connectivity of the DMN with SM and salience networks.

Chronic pain affects 1 in 5 people and has been shown to disrupt attention. Here, we investigated whether pain disrupts everyday decision making. In Study 1, 1322 participants completed two tasks online: a shopping decisions task and a measure of decision outcomes over the previous 10 years. Participants who were in pain during the study made more errors on the shopping task than those who were pain-free. Participants with a recurrent pain condition reported more negative outcomes from their past decisions than those without recurrent pain. In Study 2, 44 healthy participants completed the shopping decisions task with and without experimentally-induced pain. Participants made more errors while in pain than while pain-free. We suggest that the disruptive effect of pain on attending translates into poorer decisions in more complex and ecologically valid contexts, that the effect is causal, and that the consequences are not only attentional, but financial.

Clinicians report reluctance to deliver opioid-tapering advice to patients with chronic pain, in part due to concerns that patients will be angry and dissatisfied. An experiment was conducted to examine chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice. Patients scheduled for an initial assessment at a tertiary pain clinic and currently taking opioid medications for pain (N = 196) were randomly assigned to view video footage of a standardized patient receiving one of three forms of treatment advice: 1) stay on current medication, 2) change to a different pain medication, or 3) taper off pain medications and participate in a CBT-based pain self-management program. Participants reported how positive/enthusiastic, anxious/worried, and angry/irritable they felt in response to the simulated treatment advice, and how satisfied with and willing they would be to accept and follow the advice. Participants expressed more positive emotional and attitudinal responses to simulated opioid-tapering advice than to simulated opioid-maintenance advice. Furthermore, participants' responses to simulated opioid-tapering and opioid-change advice were not significantly different, suggesting that participants responded positively to the prospect of change in treatment strategy. Additional analyses revealed that participants with a longer history of chronic pain and opioid use responded less positively to simulated opioid-tapering advice. The results of this study contribute to our understanding of factors that may shape chronic pain patients' responses to opioid-tapering advice and suggest that patients may respond more positively to opioid tapering advice if it is presented together with an alternative treatment approach.

Pain after surgery remains a major health problem, calling for optimized treatment regimens to maximize the efficacy of pharmacological interventions. In this randomized controlled trial, we tested in a routine surgical treatment setting whether postoperative pain can be reduced by a brief preoperative intervention, i.e., positive verbal suggestions in combination with sham acupuncture, designed to optimize treatment expectations. We hypothesized that the expectancy intervention as add-on to patient-controlled intravenous analgesia (PCIA) with morphine reduces patient-reported postoperative pain and improves satisfaction with analgesia.Ninety-six women undergoing breast cancer surgery were randomized at two stages: Prior to surgery, anesthesiologists delivered either positive or neutral verbal suggestions regarding the benefits of acupuncture needling on postoperative pain ("information condition"). Patients were then randomized to receive sham acupuncture or no sham-acupuncture during postoperative care ("sham acupuncture condition"). Average pain during the 24h observation period after surgery as primary and satisfaction with analgesia as secondary outcome were assessed with standardized measures, and analyzed with ANCOVA accounting for morphine dose, surgery-related and psychological parameters.Postoperative pain ratings were significantly reduced in patients who received positive treatment-related suggestions (F=4.45, p=0.038, main effect of information). Moreover, patients who received an intervention aimed at optimized treatment expectations reported significantly greater satisfaction with analgesia (F=4.89, p=0.030, interaction effect).Together, our proof-of-concept data support that optimizing treatment expectations via verbal suggestions may offer a promising approach to improve patient-reported outcomes. Future translational and clinical studies are needed to test such psychological strategies in different surgical interventions, patient groups, and pharmacological treatment regimens.

Most studies fail to show an association between higher levels of pain-related fear and protective movement behavior in patients with chronic low back pain (CLBP). This may be explained by the fact that only general measures of pain-related fear have been used to examine the association with movement patterns. This study explored whether task-specific, instead of general measures of pain-related fear can predict movement behavior.

We have reported child anxiety sensitivity (CASI) predicts chronic post-surgical pain (CPSP). Here, we evaluated DNA methylation profiles to understand gene-environmental interactions underlying CPSP and CASI, in order to identify shared, enriched, genomic pathways. In 73 prospectively recruited adolescents undergoing spine fusion, preoperative CASI, and pain data over 12 months post-surgery were collected. DNA from peripheral blood of evaluable subjects with (n=16) and without CPSP (n=40) were analyzed using MethylationEPIC arrays. We identified 637 and 2,445 differentially methylated positions (DMPs) associated with CPSP and CASI respectively (p≤0.05). Ingenuity pathway analysis of 39 genes with DMPs for both CPSP and CASI revealed enrichment of several canonical pathways, including GABA receptor (p=0.00016 (CPSP); 0.0008 (CASI)) and Dopamine-DARPP32 Feedback in cAMP (p=0.004 (CPSP) and 0.00003 (CASI)) Signaling. Gene-gene interaction network enrichment analysis revealed participation of pathways in cell signaling, molecular transport, metabolism and neurological diseases (p-value <10-8). Bioinformatic approaches to identify histone marks and transcription factor (TF) binding events underlying DMPs, showed their location in active regulatory regions in pain pathway relevant brain cells. Using Enrichr/Pinet enrichment and Library of Integrated Network-Based Cellular Signatures (LINCS) knockdown signatures, we identified TFs regulating genes with DMPs in association with CPSP and CASI. In conclusion, we identified epigenetically enriched pathways associated with CPSP and anxiety sensitivity in children undergoing surgery. Our findings support GABA hypofunction and Dopamine-DARPP32 pathway's roles in emotion/reward and pain. This pilot study provides new epigenetic insights into the pathophysiology of CPSP, and a basis for future studies in biomarker development and targetable interventions. Perspective: Differential DNA methylation in regulatory genomic regions enriching shared neural pathways were associated with chronic post-surgical pain and anxiety sensitivity in adolescents undergoing spine surgery. Our findings support GABA hypofunction and Dopamine-DARPP32 pathway's roles in emotion/reward contributing to behavioral maintenance of pain 10-12 months after surgery.

School anxiety is a prevalent and debilitating mental health problem among youth with chronic pain. Despite evidence that anxiety in the context of school is associated with significant school-related disability, no studies have examined specific aspects of school anxiety in a pediatric chronic pain population.