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Fear of pain demonstrates significant prognostic value regarding the development of persistent musculoskeletal pain and disability. Its assessment often relies on self-report measures of pain-related fear by a variety of questionnaires. However, based either on "fear of movement/(re)injury/kinesiophobia," "fear avoidance beliefs," or "pain anxiety," pain-related fear constructs plausibly differ while it is unclear how specific the questionnaires are in assessing these different constructs. Furthermore, the relationship of pain-related fear to other anxiety measures such as state or trait anxiety remains ambiguous. Advances in neuroimaging such as machine learning on brain activity patterns recorded by functional magnetic resonance imaging might help to dissect commonalities or differences across pain-related fear constructs. We applied a pattern regression approach in 20 human patients with nonspecific chronic low back pain to reveal predictive relationships between fear-related neural pattern information and different pain-related fear questionnaires. More specifically, the applied multiple kernel learning approach allowed the generation of models to predict the questionnaire scores based on a hierarchical ranking of fear-related neural patterns induced by viewing videos of activities potentially harmful for the back. We sought to find evidence for or against overlapping pain-related fear constructs by comparing the questionnaire prediction models according to their predictive abilities and associated neural contributors. By demonstrating evidence of nonoverlapping neural predictors within fear-processing regions, the results underpin the diversity of pain-related fear constructs. This neuroscientific approach might ultimately help to further understand and dissect psychological pain-related fear constructs.
Learn More >Research in adult populations indicates that several sociodemographic and environmental variables increase risk for pain and poor outcomes. There is little research exploring the impact of household income, health insurance coverage, barriers to health care, neighborhood and school safety, violence experienced, and neighborhood isolation on pediatric chronic pain. Data from the Add Health Study, a longitudinal examination of a nationally-representative adolescent sample were analyzed. The relationships between demographic variables, risk factors, chronic pain, and long-term health outcomes were examined. Adolescents with chronic pain had lower income, more health care barriers, greater safety concerns, and experienced more violence compared to those without pain. In a model together, female sex, White race/ethnicity, and greater health care barriers, safety concerns, and violence exposure conferred significant risk for chronic pain. Additional analyses revealed nuances in the strength of risk factors between racial/ethnic groups. Systemic health care barriers were significantly associated with chronic pain and may delay symptom alleviation and return to functioning. Considering access to care is necessary in prevention efforts. Among adolescents with chronic pain, greater safety concerns predicted poor mental health outcomes, particularly for White females. The cumulative stress of environmental concerns, such as safety, and managing chronic pain may worsen functioning. PERSPECTIVE: Adolescents with chronic pain had lower income, and more health care barriers, safety concerns, and violence exposure compared to those without chronic pain. Access to care is a significant problem in youth with chronic pain. The relationships between race/ethnicity, risk factors, and health outcomes is complex and requires additional research.
Learn More >Numerous studies have demonstrated a physiological interaction between the mu opioid receptor (MOR) and delta opioid receptor (DOR) systems. A few studies have shown that dual MOR-DOR agonists could be beneficial, with reduced tolerance and addiction liability, but are nearly untested in chronic pain models, particularly neuropathic pain. In this study, we tested the MOR-DOR agonist SRI-22141 in mice in the clinically relevant models of HIV Neuropathy and Chemotherapy-Induced Peripheral Neuropathy (CIPN). SRI-22141 was more potent than morphine in the tail flick pain test, and had equal or enhanced efficacy vs. morphine in both neuropathic pain models, with significantly reduced tolerance. SRI-22141 also produced no jumping behavior during naloxone-precipitated withdrawal in CIPN or naïve mice, suggesting that SRI-22141 produces little to no dependence. SRI-22141 also reduced Tumor Necrosis Factor-α and Cyclooxygenase-2 in CIPN in the spinal cord, suggesting an anti-inflammatory mechanism of action. The DOR-selective antagonist naltrindole strongly reduced CIPN efficacy and anti-inflammatory activity in the spinal cord, without affecting tail flick antinociception, suggesting the importance of DOR activity in these models. Overall, these results provide compelling evidence that MOR-DOR agonists could have strong efficacy with reduced side effects and an anti-inflammatory mechanism in the treatment of neuropathic pain. Perspective: This study demonstrates that a MOR-DOR dual agonist given chronically in chronic neuropathic pain models has enhanced efficacy with strongly reduced tolerance and dependence, with a further anti-inflammatory effect in the spinal cord. This suggests that MOR-DOR dual agonists could be effective treatments for neuropathic pain with reduced side effects.
Learn More >Opioid prescriptions in the surgical setting have been implicated as contributors to the opioid epidemic. The authors hypothesized that a multidisciplinary approach to perioperative pain management for patients on chronic opioid therapy could decrease postoperative opioid requirements while reducing postoperative pain scores and improving functional outcomes. Therefore, a Perioperative Pain Program (PPP) for chronic opioid users was implemented. This study presents outcomes from the first 9 months of the PPP. Sixty-one patients met the inclusion criteria. Opioid consumption in morphine milligram equivalent (MME) was calculated and physical and health status of patients was assessed with the Brief Pain Inventory, Short-Form McGill Pain Questionnaire, and Short Form-12. Preliminary results showed significant reduction in MME, improved pain scores, and improved function for surgical patients on chronic opioids. PPP effectively reduced opioid usage without negatively influencing patient-reported outcomes, such as physical pain score assessment and health-related quality of life.
Learn More >Cannabis is widely used for chronic pain. However, there is some evidence of an inverse dose-response relationship between cannabis effects and pain relief which may negatively affect analgesic outcomes. In this cross-sectional survey, we examined whether daily cannabis use frequency was associated with pain severity and interference, quality of life measures relevant to pain (e.g., anxiety and depressive symptoms), and cannabis use preferences (administration routes, cannabinoid ratio). Our analysis included 989 adults who used cannabis every day for chronic pain. Participant use was designated as light, moderate, and heavy (1-2, 3-4, and 5 or more cannabis uses per day, respectively). The sample was also sub-grouped by self-reported medical only use (designated MED, n=531, 54%) vs. medical use concomitant with a past-year history of recreational use (designated MEDREC, n=458, 46%). In the whole sample, increased frequency of use was significantly associated with worse pain intensity and interference, and worse negative affect, although high frequency users also reported improved positive affect. Subgroup analyses showed that these effects were driven by MED participants. Heavy MED participant consumption patterns showed greater preference for smoking, vaporizing, and high THC products. In contrast, light MED participants had greater preference for tinctures and high CBD products. Selection bias, our focus on chronic pain, and our cross-sectional design likely limit the generalizability our results. Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as lower risk cannabis use behaviors among MED participants. Future longitudinal studies are needed to examine how high frequency of cannabis use interacts with potential therapeutic benefits. PERSPECTIVE: Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as safer use behaviors (e.g., preference for CBD and non-inhalation administration routes). These trends highlight the need for developing cannabis use guidelines for clinicians to better protect patients using cannabis.
Learn More >Daily fluctuation in pain acceptance and its impact on the physical and psychosocial functioning of individuals living with spinal cord injury (SCI) and chronic pain has not been examined. We used end-of-day (EOD) diaries and multilevel mixed effects modeling (MLM) to examine the moderating effect of within- and between-person pain acceptance on associations between pain and physical and psychosocial functioning. Individuals with SCI and chronic pain (N = 124) completed seven days of EOD diaries, which included measures of pain acceptance, pain intensity, pain catastrophizing, pain interference, participation in social roles and activities (SRA), depressive symptoms, and positive affect and well-being (PAWB). We found within-person variability in pain acceptance (28% of the total variance) and a significant moderating effect of daily fluctuation in pain acceptance on the same-day pain intensity-SRA association. Within-person changes in pain acceptance were also associated with daily changes in pain interference, depressive symptoms, and PAWB, adjusting for pain intensity and catastrophizing. Findings highlight the potential for daily or momentary assessments of pain acceptance to enhance understanding of how psychological flexibility may contribute to pain-related outcomes. Future studies could further investigate stable and variable characteristics of pain acceptance and their individual contribution to physical and psychosocial functioning. PERSPECTIVE: Daily fluctuations in pain acceptance and their association with physical and psychosocial functioning were observed in the lives of individuals with spinal cord injury (SCI) and chronic pain. These findings may guide future studies to inform the development of effective, pain acceptance-focused individualized treatment approaches for chronic pain management in people with SCI.
Learn More >The size and modular structure of versican and its gene suggests the existence of multiple splice variants. We have identified, cloned and sequenced a previously unknown exon located within the non-coding gene sequence downstream of exon 8. This exon, which we have named exon 8 specifies two stop-codons. mRNAs of the versican gene with exon 8 are predicted to be constitutively degraded by nonsense mediated RNA decay. Here we tested the hypothesis that these transcripts become expressed in a model of neuropathic pain.
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