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The relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up.
Learn More >Research on placebo analgesia commonly focuses on the impact of information about direction (i.e. increase or decrease of pain) and magnitude of the expected analgesic effect whereas temporal aspects of expectations have received little attention so far. In a recent study using short-lasting, low-intensity stimuli we demonstrated that placebo analgesia onset is influenced by temporal information. Here, we investigate whether the same effect of temporal suggestions can be found in longer lasting, high-intensity pain in a Cold Pressor Test (CPT).
Learn More >We provide national surveillance estimates of pain chronicity, severity and impact in adult subpopulations defined by both Hispanic Ancestry and Race. Data are from 144,434 adults who completed validated questionnaires in the 2010-2017 National Health Interview Survey asking about pain status within the last three (n=84,664) or six months (n=59,770). Multivariable logistic regression was used to assess the relationship between pain and ethnicity/race. Compared to White Puerto Rican participants, White participants with Central/South American and Mexican ancestry had reduced odds of reporting Category 3-4 pain and High-Impact Chronic Pain (HICP), while those of Cuban ancestry had reduced odds of only HICP – e.g., White participants with Mexican ancestry had 32% lower odds of having Category 3-4 pain and 50% lower odds of having HICP. While no differences were seen between White Puerto Rican and White Non-Hispanic participants for Category 3-4 pain, White Non-Hispanics had 40% lower odds of reporting HICP. Asian Non-Hispanic and Black Non-Hispanic participants had significantly lower odds of reporting Category 3-4 pain and HICP compared to White Puerto Rican participants, e.g., Black Non-Hispanic participants had 26% lower odds off having Category 3-4 pain and 42% lower odds of having HICP. Perspective: By examining pain status in discrete demographic groups based on Hispanic Ancestry and Race, this report further documents substantial differences in health status among underserved populations and provides a baseline for continuing surveillance research on pain, with the eventual goal of eliminating disparities in pain assessment and treatment.
Learn More >The experience of pain is a complex interaction of somatic, behavioral, affective, and cognitive components. Negative psychological states (e.g., anxiety, fear, and depression) are intertwined with pain and contribute to poorer outcomes for individuals suffering from chronic and acute pain by exacerbating the overall experience of pain and leading to increased dysfunction, disability, and distress. A need exists for efficient assessment of aversive emotional states that are associated with pain.
Learn More >Adult rats previously submitted to neonatal limited bedding (NLB), a model of early-life stress, display muscle mechanical hyperalgesia and nociceptor hyperexcitability, the underlying mechanism for which is unknown. Since voltage-gated sodium channel subtype 7 (Na1.7) contributes to mechanical hyperalgesia in several preclinical pain models and is critical for nociceptor excitability, we explored its role in the muscle hyperalgesia exhibited by adult NLB rats. Western blot analyses demonstrated increased Na1.7 protein expression in L4-L5 dorsal root ganglia (DRG) from adult NLB rats, and antisense oligodeoxynucleotide (AS ODN) targeting Na1.7 alpha subunit mRNA attenuated the expression of Na1.7 in DRG extracts. While this AS ODN did not affect nociceptive threshold in normal rats it significantly attenuated hyperalgesia in NLB rats. The selective Na1.7 activator OD1 produced dose-dependent mechanical hyperalgesia that was enhanced in NLB rats, whereas the Na1.7 blocker ProTx-II prevented OD1-induced hyperalgesia in control rats and ongoing hyperalgesia in NLB rats. AS ODN knockdown of extracellular signal-regulated kinase 1/2, which enhances Na1.7 function, also inhibited mechanical hyperalgesia in NLB rats. Our results support the hypothesis that overexpression of Na1.7 in muscle nociceptors play a role in chronic muscle pain induced by early-life stress, suggesting that Na1.7 is a target for the treatment of chronic muscle pain. PERSPECTIVE: We demonstrate that early-life adversity, induced by exposure to inconsistent maternal care, produces chronic muscle hyperalgesia, which depends, at least in part, on increased expression of Na1.7 in nociceptors.
Learn More >Findings on the short- and long-term effectiveness of intensive interdisciplinary pain treatment (IIPT) for children with severe chronic functional pain are promising. However, a definitive appraisal of long-term effectiveness cannot be made due to a lack of comparison groups. The aim of the present study was to compare the health status of former patients with the health status of an age- and sex-matched comparison group from the community.
Learn More >Chronic pain and suicidal behavior are prevalent in adolescents. This longitudinal study examined the associations between pain symptoms and suicidal behavior in adolescents. A total of 7,072 adolescents participated in a follow-up study of behavior and health in Shandong, China. A self-administered structured questionnaire was used to assess pain symptoms (headache, stomachache, and other nonspecific pain), insomnia, anxiety/depression, substance use, stressful life events, prior suicidal behavior, and family environment in November-December in 2015. One year later, a follow-up survey was conducted. Mean age of the sample was 14.6 years, and half were female. Of the sample, 44.8% and 8.4% reported having one or more pain symptoms "sometimes" and "often", respectively. A total of 22.4% and 10.6% reported having lifetime suicidal behavior at baseline and subsequent suicidal behavior over the 1-year follow-up, respectively. Frequent pain was significantly associated with increased risk of suicidal behavior at baseline (OR=1.64, 95%CI=1.32-2.03) and during the subsequent year (OR=1.50, 95%CI=1.17-1.93) while adjusting for covariates. Among adolescents without a history of prior suicidal behavior, frequent pain was significantly associated with an approximately 70% increased risk of incident suicidal behavior (OR= 1.69, 95%CI=1.14-2.51). In conclusion, frequent pain appears to be predictive of adolescent suicidal behavior while adjusting for family and personal psychosocial covariates. PERSPECTIVE: This article presents the prospective associations of frequent pain symptoms with suicidal behavior in adolescents. Frequent pain was associated with a 50-70% increased risk of suicidal behavior 1 year later. The finding underscores the importance of pain assessment and treatment in comprehensive suicide prevention efforts in adolescents.
Learn More >Pruritus is a common symptom of inflammatory skin conditions, including atopic dermatitis (AD). Although primary sensory neurons that transmit pruritic signals are well-cataloged, little is known about the neuronal alterations that occur as a result of skin disruption in AD. To address this question, we examined the molecular and behavioral consequences of challenging mice, which overexpress PAR2 in suprabasal keratinocytes, with serial topical application of the environmental allergen house dust mite (HDM). We monitored behavior and used RNA sequencing, qPCR, and in situ hybridization to evaluate gene expression in trigeminal ganglia (TG), before and after HDM. We found that neither nor wild-type (WT) mice exhibited spontaneous scratching, and pruritogen-induced acute scratching did not differ. In contrast, HDM exacerbated scratching in mice. Despite the absence of scratching in untreated mice, several TG genes in these mice were up-regulated compared to WT. HDM treatment of the mice enhanced up-regulation of this set of genes and induced additional genes, many within the subset of TG neurons that express TRPV1. The same set of genes was up-regulated in HDM-treated mice that did not scratch, but at lesser magnitude. Finally, we recorded comparable transcriptional changes in IL31Tg mice, demonstrating that a common genetic program is induced in two AD models. Taken together, we conclude that transcriptional changes that occur in primary sensory neurons in dermatitis-susceptible animals underlie a genetic priming that not only sensitizes the animal to chronic allergens but also contributes to pruritus in atopic skin disease.
Learn More >A growing body of evidence supports the modulation of pain by light exposure. As such, phototherapy is being increasingly utilized for the management of a variety of pain conditions. The modes of delivery, and hence applications of phototherapy, vary by wavelength, intensity, and route of exposure. As such, differing mechanisms of action exist depending upon those parameters. Cutaneous application of red light (660nm) has been shown to reduce pain in neuropathies and complex regional pain syndrome-I, whereas visual application of the same wavelength of red light has been reported to exacerbate migraine headache in patients and lead to the development of functional pain in animal models. Interestingly visual exposure to green light can result in reduction in pain in variety of pain conditions such as migraine and fibromyalgia. Cutaneous application typically requires exposure on the order of minutes, whereas visual application requires exposure on the order of hours. Both routes of exposure elicit changes centrally in the brainstem and spinal cord, and peripherally in the dorsal root ganglia and nociceptors. The mechanisms of photobiomodulation of pain presented in this review provide a foundation in furtherance of exploration of the utility of phototherapy as a tool in the management of pain. PERSPECTIVE: This review synopsizes the pathways and mechanisms through which light modulates pain and the therapeutic utility of different colors and exposure modalities of light on pain. Recent advances in photobiomodulation provide a foundation for understanding this novel treatment for pain on which future translational and clinical studies can build upon.
Learn More >Acid-sensing ion channels (ASICs) are expressed in the nervous system, activated by acidosis, and implicated in pain pathways. Mambalgins are peptide inhibitors of ASIC1 and analgesic in rodents via inhibition of centrally expressed ASIC1a and peripheral ASIC1b. This activity has generated interest in mambalgins as potential therapeutics. However, most mechanism and structure-activity relationship work on mambalgins has focused on ASIC1a, and neglected the peripheral analgesic target ASIC1b. Here, we compare mambalgin potency and mechanism of action at heterologously expressed rat and human ASIC1 variants. Unlike the nanomolar inhibition at ASIC1a and rodent ASIC1b, we find mambalgin-3 only weakly inhibits human ASIC1b and ASIC1b/3 under severe acidosis, but potentiates currents under mild/moderate acidosis. Our data highlight the importance of understanding the activity of potential ASIC-targeting pharmaceuticals at human channels.
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