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Naltrexone reversibly blocks the effects of opioids and has been shown to decrease placebo analgesia. However, it is not clear (1) to what extent naltrexone affects pain modulation in a nontreatment context, for example, in response to pain cues or (2) how naltrexone given prior to pain-cue learning shapes pain responses. In a double-blind procedure prior to pain-cue conditioning, 30 healthy participants were randomized to receive an oral dose of naltrexone (50 mg) or inert pill. During functional magnetic resonance imaging, high and low pain pressures were paired with two different visual cues: a high pain cue and a low pain cue (learning sequence). During a test sequence, medium levels of pressure were used for both cues and the difference in subjective pain ratings following high and low pain cues was calculated. Results showed significant conditioned pain responses across groups (<.001); however, no significant difference between participants receiving naltrexone or inert pill (=.193). There was a significant correlation between the difference in high and low pain ratings during the learning sequence and the effect of high and low pain cues during the test sequence (r = .575, =.002). Functional magnetic resonance imaging analyses revealed no significant difference in brain activation between groups. Here, we demonstrate comparable learning of pain responses in participants treated with naltrexone or inert pill. The results point to the possibility that associative learning, and conditional responding to pain cues, is not dependent on endogenous opioids. Our results, using pain-cue conditioning to create reduced pain responses, contrast previous studies where opioid antagonists significantly reduced the placebo effect in treatment of pain.
Learn More >This study investigated the safety and efficacy of mirogabalin, a novel, potent, selective ligand of the α2δ subunit of voltage-dependent Ca channels, for the treatment of postherpetic neuralgia (PHN). In this multicenter, double-blind, placebo-controlled phase 3 study, Asian patients ≥20 years with PHN were randomized 2:1:1:1 to placebo or mirogabalin 15, 20, or 30 mg/day for up to 14 weeks (NCT02318719). The primary efficacy endpoint was the change from baseline in average daily pain score at week 14, defined as a weekly average of daily pain (0 = "no pain" to 10 = "worst possible pain," for the last 24 hours). Of 765 patients randomized, 763 received ≥ 1 dose of the study drug and were included in the analysis; 303, 152, 153, and 155 received placebo, mirogabalin 15, 20, or 30 mg/day, respectively. A total of 671 (87.7%) patients completed the study. At week 14, the difference in average daily pain score least squares mean vs placebo was -0.41, -0.47, and -0.77, respectively; all mirogabalin groups showed statistical significance. The most common treatment-emergent adverse events were somnolence, nasopharyngitis, dizziness, weight increase, and edema, and all of them were mild or moderate in severity. Mirogabalin was superior to placebo in all groups for relieving PHN and appeared well tolerated.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Normative data for chronic pain questionnaires are essential to the interpretation of aggregate scores on these questionnaires, for both clinical trials and clinical practice. In this study we summarised data from 13,343 heterogeneous patients on several commonly used pain questionnaires that were routinely collected from 36 pain clinics in Australia and New Zealand as part of the electronic Persistent Pain Outcomes Collaboration (ePPOC) including the Brief Pain Inventory (BPI); the Depression Anxiety and Stress Scales (DASS); the Pain Self-Efficacy Questionnaire (PSEQ); and the Pain Catastrophizing Scale (PCS). The data are presented as summarised normative data, broken down by demographic (age, sex, work status, etc) and pain site/medical variables. The mean BPI severity score was 6.4 (moderate-severe) and mean interference score was 7.0. The mean DASS depression score was 20.2 (moderate-severe), mean DASS anxiety was 14.0 (moderate), and mean DASS stress was 21.0 (moderate). The mean PCS scores were 10.0, 5.9, 14.1 and 29.8 for rumination, magnification, helplessness and total, respectively. The mean PSEQ score was 20.7. Males had slightly worse scores than females on some scales. Scores tended to worsen with age until 31-50 years, after which they improved. Scores were worse for those who had a greater number of pain sites, were unemployed, were injury compensation cases, or whose triggering event was a motor vehicle accident or injury at work or home. These results and comparisons with data on the same measures from other countries, as well as their uses in both clinical practice and clinical trials, are discussed.
Learn More >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 >The present study investigates how participants' locus of control and their family and friends' validation of their pain influences participants' chronic pain experiences. Four thousand, 25 adults were recruited through the Chronic Pain In America survey. Results show that individuals who endorse an internal locus of control and experience family and friends' validation of their chronic pain reported better chronic pain outcomes and less negative life impact due to chronic pain. The current results indicate the locus of control and family and friends' validation of chronic pain experience plays an important role in chronic pain and the impact of chronic pain across the life course.
Learn More >Despite the known involvement of depression in chronic pain, the association between persistence with and adherence to antidepressant medication and onset of chronic pain in patients with depression remains unclear.
Learn More >More patients are turning to medical marijuana as an alternative treatment, yet there are apparent knowledge gaps on the risk benefit of medical marijuana for a variety of indications. This study aimed to determine the priorities for medical marijuana research from the perspective of multiple stakeholders including patients, clinicians, and industry representatives.
Learn More >Allergic rhinitis symptoms can be reduced by behaviorally conditioning antihistamine. It is unclear whether these findings extend to histamine-induced itch, or work when participants are informed about the conditioning procedure (open-label conditioning). The current study aims to investigate the efficacy of (open-label) antipruritic behavioral conditioning for histamine-induced itch.
Learn More >Gerontological research reveals considerable interindividual variability in aging phenotypes, which has motivated research efforts to identify 'aging biomarkers.' Aging biomarkers are used to calculate biological age, which are better predictors of disease risk and residual lifespan when compared to chronological age alone. Emerging evidence using the epigenetic clock as an aging biomarker supports highly reliable individualized predictions about future health. The current study aimed to determine whether an epigenetic aging biomarker was associated with chronic pain in older adults (60-83 years old). A subset of participants (n=29) in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study underwent a blood draw, demographic, psychological, cognitive and pain assessments. We estimated Horvath's epigenetic clock and calculated the difference between epigenetic age and chronological age that has been previously reported to predict overall mortality risk. Older individuals without chronic pain (n=9) had significantly "younger" epigenetic age compared to those with chronic pain (n=20, p<0.05). Older epigenetic age was associated with greater pain during daily activities (r=0.494, p=0.010) and anatomical pain sites (r=0.741, p<0.001), but not pain frequency/duration. An older epigenetic age was also associated with higher vibratory detection thresholds (r=0.490, p=0.021), heat pain thresholds (r=-0.478, p=0.028), and pressure pain thresholds at the trapezius (r=-0.571, p=0.006), but not thermal detection, pressure pain at the quadriceps or pain inhibition (p's>0.05). Epigenetic aging was associated with greater emotional stability (r=-0.461, p=0.027), conscientiousness (r=-0.549, p=0.007) and lower extraversion (r=0.414, p=0.049), but not depression or affect (p's>0.05). Epigenetic aging was also associated with lower episodic (r=-0.698, p=0.001) and working memory (r=-0.760, p<0.001). Our findings suggest that chronic pain is associated with accelerated epigenetic aging in healthy, community-dwelling older individuals and future studies with larger samples are needed to confirm our findings. An aging biomarker such as the epigenetic clock may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.
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