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Background and aims Recognition of the biopsychosocial aspects of pain is important for a true understanding of the burden of pain and the necessity of pain management. Biopsychosocial aspects of pain may differ between countries and cultures. Market research methods can be well suited and effective for assessing patient perspectives of pain and biopsychosocial differences. We conducted and combined 3 cross-sectional, international surveys to document the impact of pain on physical and emotional aspects of life, as well as quality of life (QOL). Methods Online panelists from 24 countries took part in our surveys in 2014, 2016, and 2017. Fourteen countries (Australia, Brazil, Canada, China, Germany, Italy, Japan, Poland, Russia, United Kingdom, United States, Mexico, Sweden, Saudi Arabia) contributed data in all 3 surveys and comprise the analysis population. A Global Pain Index (GPI) was constructed using 8 questions in 3 categories: Physical (frequency, duration, intensity of pain), Emotional (anxiety, impact on self-esteem, happiness), and Impact on QOL and ability to enjoy life. Each item was scored as the percentage of respondents meeting a prespecified threshold indicative of a substantial pain impact. Scores for the items within each category were averaged to obtain a category score, category scores were averaged to obtain a total score for each survey, and total scores from each survey were averaged to obtain a final combined score. Scores were assessed for the overall population, by individual countries, by age and gender, and by self-identified pain-treatment status (treat immediately, wait, never treat). Results Of the 50,952 adult respondents, 28,861 (56.6%) had ever experienced musculoskeletal pain; 50% of those with pain had pain with a multifaceted impact based on the GPI (Physical: 51%; Emotional: 40%; QOL Impact: 59%). Russia (57%) and Poland (56%) had the highest scores; Mexico (46%), Germany (47%), and Japan (47%) had the lowest. GPI score was higher in women (52%) than men (48%), and initially increased with age through age 54 (18‒24 years: 45%; 25‒34 years: 52%; 35‒44 years: 53%; 45‒54 years: 54%), after which it decreased again (55‒64 years: 51%; ≥65 years: 45%). A majority (65%) of respondents wait to treat their pain, whereas 21% treat their pain immediately and 14% never treat pain. The most common reason for waiting (asked in survey 3 only) was to avoid taking medication. Conclusions In this combined analysis of 3 international surveys using a novel biopsychosocial pain assessment tool, pain had a substantial impact on ~50% of respondents' lives, spanning physical (51%), emotional (40%), and QOL effects (59%). Despite the substantial impact, a majority of patients tried to avoid treating their pain. Implications Clinicians should take a biopsychosocial approach to pain by asking patients not only about the presence and severity of pain, but the extent to which it affects various aspects of their lives and daily functioning. Patients may also need education about the efficacy and safety of available treatments for self-management of pain. The GPI may be a useful new tool for future studies of the biopsychosocial effects of pain in large populations.
Learn More >The descending serotonergic pathway, from the brainstem to spinal cord, modulates various aspects of pain processing. The spinal 5-hydroxytryptamine (5-HT) and 5-HT receptors play pivotal roles in pain modulation. Perospirone is a novel atypical antipsychotic that serves as a 5-hydroxytryptamine (5-HT) receptor agonist, a 5-HT receptor antagonist, and a dopamine D receptor antagonist. Little is known about the effect of perospirone on pain transmission. Here, we explored whether perospirone attenuated neuropathic and inflammatory pain in the spinal cord. A chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal administration of perospirone (10, 20, or 40 μg) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin test and for motor coordination employing the rotarod test. To define the mechanism underlying the action of perospirone, the effects of intrathecal pretreatment with the 5-HT receptor antagonist WAY-100635, the 5-HT receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI), and the dopamine D receptor agonist sumanirole on perospirone action were examined using the electronic von Frey test and cold plate test. Perospirone dose-dependently alleviated mechanical and cold hyperalgesia, but not inflammatory nociception in the spinal cord, and affected motor coordination. WAY-100635 reversed the antihyperalgesic action of perospirone significantly, but neither DOI nor sumanirole exhibited such an effect. We conclude that perospirone attenuates mechanical and cold hyperalgesia principally via 5-HT receptor activation in the spinal cord, and the agent is a promising novel candidate for neuropathic pain relief.
Learn More >To investigate the relationship of emotion regulation strategies (i.e., emotional suppression and reappraisal) with pain catastrophizing, fear of pain, pain intensity, worry, and depression as function of age in samples of older and younger adults.
Learn More >Chronic pruritus is a cardinal symptom of the inflammatory skin disease atopic dermatitis (AD). Pathogenic mechanisms in the periphery, spinal cord and the brain have been implicated in AD-related pruritus. Therefore, both systemic and topical administration of drugs could potentially provide relief. Despite efforts to elucidate the mechanisms behind AD-related pruritus and the relative contribution of peripheral nervous system and central nervous system (CNS), specific and successful treatment options have not yet been developed. Several small molecule drugs are currently being investigated to treat AD and AD-related pruritus. These small molecule drugs can be applied systemically but also topically, as they are able to penetrate into the skin due to their small size. Small molecule drugs specifically targeting peripheral itch transmission, e.g. peripherally selective κ-opioid receptors agonists and neurokinin 1 receptors antagonists, have so far been unable to improve AD-related pruritus when applied systemically, possibly because of the lack of CNS activity. Current evidence from clinical and preclinical trials with centrally acting or peripherally selective oral κ-opioid receptors agonists implies that CNS activity is required for an antipruritic effect. CNS activity is, however, directly associated with CNS-mediated side-effects. On the other hand, topical application of small molecules with anti-inflammatory activity such as Janus kinase inhibitors and phosphodiesterase 4 inhibitors, and also of κ-opioid receptor agonists, has shown promising results regarding their ability to reduce AD-related pruritus. In conclusion, topical application of anti-inflammatory compounds appears to be a highly promising strategy for the treatment of AD-related pruritus.
Learn More >Electroencephalography During Nociceptive Stimulation in Chronic Pain Patients: A Systematic Review.
With its high temporal resolution, electroencephalography (EEG), a technique that records electrical activity of cortical neuronal cells, is a potentially suitable technique to investigate human somatosensory processing. By using EEG, the processing of (nociceptive) stimuli can be investigated, along with the functionality of the nociceptive pathway. Therefore, it can be applied in chronic pain patients to objectify whether changes have occurred in nociceptive processing. Typically, so-called event-related potential (ERP) recordings are used, where EEG signals are recorded in response to specific stimuli and characterized by latency and amplitude.
Learn More >Preclinical research using different rodent model systems has largely contributed to the scientific progress in the pain field, however, it suffers from interspecies differences, limited access to human models, and ethical concerns. Human induced pluripotent stem cells (iPSCs) offer major advantages over animal models, i.e., they retain the genome of the donor (patient), and thus allow donor-specific and cell-type specific research. Consequently, human iPSC-derived nociceptors (iDNs) offer intriguingly new possibilities for patient-specific, animal-free research. In the present study, we characterized iDNs based on the expression of well described nociceptive markers and ion channels, and we conducted a side-by-side comparison of iDNs with mouse sensory neurons. Specifically, immunofluorescence (IF) analyses with selected markers including early somatosensory transcription factors (BRN3A/ISL1/RUNX1), the low-affinity nerve growth factor receptor (p75), hyperpolarization-activated cyclic nucleotide-gated channels (HCN), as well as high voltage-gated calcium channels (VGCC) of the Ca2 type, calcium permeable TRPV1 channels, and ionotropic GABA receptors, were used to address the characteristics of the iDN phenotype. We further combined IF analyses with microfluorimetric Ca measurements to address the functionality of these ion channels in iDNs. Thus, we provide a detailed morphological and functional characterization of iDNs, thereby, underpinning their enormous potential as an animal-free alternative for human specific research in the pain field for unveiling pathophysiological mechanisms and for unbiased, disease-specific personalized drug development.
Learn More >Exercise and spinal manipulative therapy are commonly used for the treatment of chronic low back pain (CLBP) in Australia. Reduction in pain intensity is a common outcome; however, it is only one measure of intervention efficacy in clinical practice. Therefore, we evaluated the effectiveness of two common clinical interventions on physical and self-report measures in CLBP. Participants were randomized to a 6‑month intervention of general strength and conditioning (GSC; = 20; up to 52 sessions) or motor control exercise plus manual therapy (MCMT; =20; up to 12 sessions). Pain intensity was measured at baseline and fortnightly throughout the intervention. Trunk extension and flexion endurance, leg muscle strength and endurance, paraspinal muscle volume, cardio‑respiratory fitness and self-report measures of kinesiophobia, disability and quality of life were assessed at baseline and 3- and 6-month follow-up. Pain intensity differed favoring MCMT between-groups at week 14 and 16 of treatment (both, = 0.003), but not at 6-month follow‑up. Both GSC (mean change (95%CI): -10.7 (-18.7, -2.8) mm; = 0.008) and MCMT (-19.2 (-28.1, -10.3) mm; < 0.001) had within-group reductions in pain intensity at six months, but did not achieve clinically meaningful thresholds (20mm) within- or between‑group. At 6-month follow-up, GSC increased trunk extension (mean difference (95% CI): 81.8 (34.8, 128.8) s; = 0.004) and flexion endurance (51.5 (20.5, 82.6) s; = 0.004), as well as leg muscle strength (24.7 (3.4, 46.0) kg; = 0.001) and endurance (9.1 (1.7, 16.4) reps; = 0.015) compared to MCMT. GSC reduced disability (-5.7 (‑11.2, -0.2) pts; = 0.041) and kinesiophobia (-6.6 (-9.9, -3.2) pts; < 0.001) compared to MCMT at 6‑month follow-up. Multifidus volume increased within-group for GSC ( = 0.003), but not MCMT or between-groups. No other between-group changes were observed at six months. Overall, GSC improved trunk endurance, leg muscle strength and endurance, self-report disability and kinesiophobia compared to MCMT at six months. These results show that GSC may provide a more diverse range of treatment effects compared to MCMT.
Learn More >Chronic low back pain (cLBP) is a common disorder with unsatisfactory treatment options. Acupuncture has emerged as a promising method for treating cLBP. However, the mechanism underlying acupuncture remains unclear. In this study, we investigated the modulation effects of acupuncture on resting state functional connectivity (rsFC) of the periaqueductal gray (PAG) and ventral tegmental area (VTA) in patients with cLBP. Seventy-nine cLBP patients were recruited and assigned to four weeks of real or sham acupuncture. Resting state functional magnetic resonance imaging data were collected before the first and after the last treatment. Fifty patients completed the study. We found remission of pain bothersomeness in all treatment groups after four weeks, with greater pain relief after real acupuncture compared to sham acupuncture. We also found that real acupuncture can increase VTA/PAG rsFC with the amygdala, and the increased rsFC was associated with decreased pain bothersomeness scores. Baseline PAG-amygdala rsFC could predict four-week treatment response. Our results suggest that acupuncture may simultaneously modulate the rsFC of key regions in the descending pain modulation (PAG) and reward systems (VTA), and the amygdala may be a key node linking the two systems to produce antinociceptive effects. Our findings highlight the potential of acupuncture for chronic low back pain management.
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