PAIN®最新文献

Abstract: Virtual reality (VR) is a promising intervention for both experimentally induced and clinical pain, but the factors contributing to the efficacy of VR remain relatively unclear, partially because selecting adequate controls in existing VR studies is challenging. Here, we identified and isolated several factors potentially influencing the hypoalgesic effect of VR. In this within-subjects, counterbalanced controlled study, healthy participants received painful heat stimulation under 5 conditions: VR Ocean (immersive ocean environment), Sham VR Ocean (nonimmersive ocean environment), VR Neutral (immersive neutral environment), Imagination (self-imagined ocean environment), and No-intervention. Participants underwent a pain tolerance test under each condition, stopping the heat stimulation when they reached their maximum tolerance. Participants were also divided into a group with information highlighting the VR Ocean as a highly effective intervention, and a control group receiving no such information. Results showed that pain tolerance, expressed in degree Celsius, was significantly higher in the VR Ocean condition compared with all other conditions, despite VR Ocean not attenuating self-reported pain intensity and disengagement from pain. In addition, VR Ocean decreased pain unpleasantness relative to all conditions except Sham VR Ocean. Virtual reality Ocean also improved mood relative to all other conditions and was perceived as the most engaging. Expectations did not affect the results. Taken together, we found that being immersed in an externally generated pleasant environment is key to the hypoalgesic effect of VR. Virtual reality is effective in increasing the level of pain being tolerated and mitigating the subjective affective experience of pain.

Abstract: Whiplash injury is associated with high socioeconomic costs and poor prognosis. Most people are classified as having whiplash-associated disorder grade II (WADII), with neck complaints and musculoskeletal signs, in the absence of frank neurological signs. However, evidence suggests that there is a subgroup with underlying nerve involvement in WADII, such as peripheral neuroinflammation. This study aimed to investigate the presence of neuroinflammation in acute WADII using T2-weighted magnetic resonance imaging of the brachial plexus, dorsal root ganglia and median nerve, and clinical surrogates of neuroinflammation: heightened nerve mechanosensitivity (HNM), raised serum inflammatory mediators, and somatosensory hyperalgesia. One hundred twenty-two WADII participants within 4 weeks of whiplash and 43 healthy controls (HCs) were recruited. Magnetic resonance imaging T2 signal ratio was increased in the C5 root of the brachial plexus and the C5-C8 dorsal root ganglia in WADII participants compared with HCs but not in the distal median nerve trunk. Fifty-five percent of WADII participants had signs of HNM. Inflammatory mediators were also raised compared with HCs, and 47% of WADII participants had somatosensory changes on quantitative sensory testing. In those WADII individuals with HNM, there was hyperalgesia to cold and pressure and an increased proportion of neuropathic pain. Many people with WADII had multiple indicators of neuroinflammation. Overall, our results present a complex phenotypic profile for acute WADII and provide evidence suggestive of peripheral neuroinflammation in a subgroup of individuals. The results suggest that there is a need to reconsider the management of people with WADII.

Abstract: Immune cells play a critical role in the transition from acute to chronic pain. However, the role of mast cells in pain remains underinvestigated. Here, we demonstrated that the resolution of inflammatory pain is markedly delayed in mast cell-deficient mice. In response to complete Freund adjuvant, mast cell-deficient mice showed greater levels of nitric oxide, leukocyte infiltration, and altered cytokine/chemokine profile in inflamed skin in both sexes. In wild-type mice, the number of mast cell and mast cell-derived chymases, chymase 1 (CMA1) and mast cell protease 4 (MCPT4), increased in the inflamed skin. Inhibiting chymase enzymatic activity delayed the resolution of inflammatory pain. Consistently, local pharmacological administration of recombinant CMA1 and MCPT4 promoted the resolution of pain hypersensitivity and attenuated the upregulation of cytokines and chemokines under inflammation. We identified CCL9 as a target of MCPT4. Inhibition of CCL9 promoted recruitment of CD206+ myeloid cells and alleviated inflammatory pain. Our work reveals a new role of mast cell-derived chymases in preventing the transition from acute to chronic pain and suggests new therapeutic avenues for the treatment of inflammatory pain.

Abstract: Back pain is a common and recurrent health complaint in adolescence. Psychosocial factors may be associated with the onset and persistence of back pain symptoms. This systematic review aims to determine the association between bullying victimization and back pain in young people. Observational studies that quantified the association between bullying victimization and back pain in participants were included in this systematic review. Estimates of associations and confidence intervals were extracted. A random effects meta-analysis of estimates of association was performed. The quality of evidence was assessed using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Database searches yielded 18,311 citations. Nineteen studies (n = 212,058, 51.4% female) were included in our review. Meta-analysis showed a positive association between bullying victimization and back pain (odds ratio 1.93, confidence interval 1.75-2.13). Subgroup analysis showed no statistically significant effect of sex, age, bullying type, pain type, recall periods, bullying frequency, back pain frequency, risk estimate adjustment, and study critical appraisal rating. All studies were rated at moderate-high risk of bias. Our synthesis of evidence found a weak-moderate association between bullying victimization and back pain in young people. Methodological shortcomings and heterogeneity in the field limit causal inference. Future longitudinal studies are required.

Abstract: Repetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. Ischemia with reperfusion injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity caused by I/R injury may be due to sex-specific gene expression in the dorsal root ganglia (DRG) and distinct upregulation of growth factors and cytokines in the affected muscles. To determine how these unique gene expression programs may be established in a sex-dependent manner in a model that more closely mimics clinical scenarios, we used a developed prolonged ischemic myalgia model in mice whereby animals experience repeated I/R injuries and compared behavioral results with unbiased and targeted screening strategies in male and female DRG. Several distinct proteins were found to be differentially expressed in male and female DRG, including phosphorylated AU-rich element RNA-binding protein (pAUF1), which is known to regulate gene expression. Nerve-specific siRNA-mediated knockdown of AUF1 inhibited prolonged hypersensitivity in females only, whereas overexpression of AUF1 in male DRG neurons increased pain-like responses. AUF1 knockdown was able to specifically inhibit repeated I/R-induced gene expression in females potentially downstream of prolactin receptor signaling. Data suggest RNA-binding proteins such as pAUF1 may underlie the sex-specific effects on DRG gene expression that modulates behavioral hypersensitivity after repeated I/R injury through prolactin signaling. This study may aid in finding distinct receptor differences related to the evolution of acute to chronic ischemic muscle pain development between sexes.

Abstract: One-fifth of US adults experience chronic pain, which is associated with increased tobacco and cannabis use. Although bidirectional relationships between tobacco and pain have been demonstrated, pathways between pain, cannabis use, and co-use of cannabis and tobacco are understudied. We aimed to estimate the effects of (1) substance use (exclusive and co-use of cannabis and tobacco) on later pain intensity, and (2) pain intensity on later substance use. Data were from 31,983 adults in biennial surveys (2015-2021) of the US nationally representative longitudinal Population Assessment of Tobacco and Health Study (n = 71,055 pairs of consecutive surveys; T1 and T2). Past-week pain intensity was dichotomized (≤4/10 no/low pain; >4/10 moderate/severe pain). Mutually exclusive substance use categories (past 30 days) were no cannabis/tobacco use; exclusive cannabis/tobacco use; and co-use. Logistic regression assessed whether T1 substance use affected moderate/severe pain at T2. Multinomial models assessed whether pain status at T1 affected substance use at T2. Compared with no cannabis/tobacco use at T1, co-use (OR: 2.29 [95% CI: 2.09-2.51]), exclusive tobacco use (2.00 [1.86-2.14]), and exclusive cannabis use (1.35 [1.13-1.61]) were all associated with moderate/severe pain at T2. Moderate/severe pain at T1 increased odds of co-use (2.43 [2.22-2.66]), exclusive tobacco (2.12 [1.98-2.28]), and exclusive cannabis use (1.46 [1.29-1.65]) compared with no cannabis/tobacco use at T2, and increased odds of co-use at T2 compared with exclusive cannabis/tobacco use. Findings demonstrated bidirectional relationships between pain and the exclusive use and co-use of cannabis and tobacco and indicate potential synergy in the co-use of cannabis and tobacco with respect to pain.

Abstract: Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. Data from 58 participants were included in study 1 (chronic pain n = 34, pain free n = 24, mean age = 16 years), and 39 participants were included in study 2 (chronic pain n = 26, pain free n = 13, mean age = 16 years). Both studies used a threat-safety learning paradigm with memory recall (≈1 month later). Participants completed structural and functional (resting-state) magnetic resonance imaging, salivary cortisol measurements, and self-report measures. Adolescents with pain and pain-free peers consistently recalled being more afraid of safety cues (CS-) and, during heightened stress at encoding (higher cortisol levels), also reported being more afraid of threat cues (CS+). However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain.

Abstract: Prescription opioids for noncancer pain in the United Kingdom have increased over the past 2 decades, alongside associated harms. Policies addressing opioid prescribing must be tailored to individual patient needs with specific disease systems. The aim of this study was to evaluate clinical conditions associated with new opioid initiation in noncancer pain using nationally representative UK data. Primary care electronic health records from January 1, 2006, to September 31, 2021, were used from the Clinical Research Practice Datalink to identify incident opioid prescriptions. Patient histories were reviewed using code lists for opioid-related conditions with a 5-year look-back for chronic conditions and a 1-year look-back for surgical indications before opioid initiation. In total, 3,030,077 new opioid use episodes in 2,027,402 patients were identified, with 61% being women, 77% aged 45 years and older, and 48% from the highest deprivation quintile. Ten systems associated with opioid initiation were identified, which were not mutually exclusive, as patients could have opioids prescribed for multiple indications. The most common were musculoskeletal (80.8%), respiratory (57.6%), infections (30.4%), trauma/injury (20.4%), neurology (19.9%), and postsurgical indications (5.5%). Osteoarthritis (60.7%) and low back pain (41.0%) were the most frequent musculoskeletal conditions. Orthopedic surgeries accounted for 41.2% of all postsurgical indications. This is the first study in the United Kingdom evaluating large-scale national data to assess indications associated with opioid initiation. Nearly 3 quarters of new opioid prescriptions for noncancer pain were in patients with musculoskeletal conditions, often for conditions with limited evidence for opioid efficacy. These findings could inform targeted interventions and future policies to support nonpharmacological interventions in the most common conditions where opioid harms outweigh benefits.