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To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method.
Learn More >Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-EM structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with Protoxin-II and saxitoxin with Huwentoxin-IV, both determined at overall resolutions of 3.2 Å. The two structures are nearly identical except for minor shifts of VSD, whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional Protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics.
Learn More >Functional abdominal pain disorders (FAPD) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age-and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. CPM was recorded as an increase in the pressure pain threshold at the trapezius test site in response to experimental conditioning pain imposed by the cold pressure task (12°C ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower pressure pain thresholds at all test sites (P<0.05), a lower CPM response (P=0.02), more functional disability (P<0.001) and pain-related fear (P<0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P<0.001). No sex differences were found for the experimental pain measurements (P>0.05), nor was there a significant correlation between the child-and parent questionnaires and the CPM-effect (P>0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.
Learn More >Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at six months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate and severe interference) as a dependent three-stage factor. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Of 2,322 patients, 15.3% reported CPSP with an average pain score ≥3 (NRS 0-10). Risk for a higher PITS group increased by 190% (OR (95%-CI): 2.9 (2.7-3.2); p<0.001) in patients with, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 (1.12-1.45), p<0.001). Pre-existing chronic pain (3.6 (2.6-5.1); p<0.001), time spent in severe acute pain (2.9 (1.3-6.4); p=0.008), neurosurgical back surgery in males (3.6 (1.7-7.6); p<0.001) and orthopedic surgery in females (1.7 (1.0-3.0); p=0.036) were the variables with strongest association with PITS. PITS might provide more precise information about patients' outcomes than pain scores only. As neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.
Learn More >The role of sex hormones on postsurgical pain perception is basically unclear. Here we studied the role of endogenous gonadal hormones for pain and hyperalgesia in human volunteers after experimental incision.A 4-mm incision was made in the volar forearm of 15 female volunteers both in the follicular and the luteal phase (random block design). Somatosensory profiles were assessed at baseline and 1-72 h after incision by quantitative sensory testing (QST), compared between both cycle phases and related to individual plasma levels of gonadal hormones.Sensory testing at baseline revealed significantly lower pain thresholds (25 vs. 46 mN, p<0.005) and increased pain ratings to pinprick (0.96 vs. 0.47, p<0.0001) in the luteal phase; similar, one hour after incision, pain intensity to incision (38 vs. 21/100, p<0.005), pinprick hyperalgesia by rating (p<0.05) and area of secondary hyperalgesia (p<0.001) were enhanced in the luteal phase. Multiple regression analysis revealed that pinprick pain sensitivity at baseline was significantly predicted by progesterone (partial r= 0.67, p<0.001), FSH (partial r=0.61, p<0.005) and negatively by testosterone (partial r=-0.44, p<0.05). Likewise, incision-induced pain and pinprick hyperalgesia (rating and area) were significantly predicted by progesterone (partial r=0.70, r=0.46 and r=0.47, respectively; p<0.05-0.0001) and in part by FSH; the contribution of estrogen, however, was fully occluded by progesterone for all measures.In conclusion, pinprick pain as well as incision-induced pain and mechanical hyperalgesia were greater in the luteal phase and predicted by progesterone suggesting a major role for progesterone. Other hormones involved are testosterone (protective) and in part FSH.
Learn More >Sleep loss increases the experience of pain. However, the brain mechanisms underlying altered pain processing following sleep deprivation are unknown. Moreover, it remains unclear whether ecologically modest night-to-night changes in sleep, within an individual, confer consequential day-to-day changes in experienced pain. Here, we demonstrate that acute sleep-deprivation amplifies pain reactivity within human (male and female) primary somatosensory cortex yet blunts pain-reactivity in higher-order valuation and decision-making regions of the striatum and insula cortex. Consistent with this altered neural signature, we further show that sleep deprivation expands the temperature range for classifying a stimulus as painful, specifically through a lowering of pain thresholds. Moreover, the degree of amplified reactivity within somatosensory cortex following sleep deprivation significantly predicts this expansion of experienced pain across individuals. Finally, outside of the laboratory setting, we similarly show that even modest nightly changes in sleep quality (increases and decreases) an individual determine consequential day-to-day changes in experienced pain (decreases and increases, respectively). Together, these data provide a central brain framework underlying the impact of sleep loss on pain, and furthermore, establish that the association between sleep and pain is expressed in a night-to-day, bidirectional relationship within a sample of the general population. More broadly, our findings highlight sleep as a novel therapeutic target for pain management within and outside the clinic, including circumstances where sleep is frequently short yet pain is abundant (e.g. the hospital setting).Are you experiencing pain? Did you have a bad night of sleep? This study provides underlying brain and behavioral mechanisms explaining this common co-occurrence. We show that sleep deprivation enhances pain responsivity within the primary sensing regions of the brain's cortex yet blunts activity in other regions that modulate pain processing-the striatum and insula. We further establish that even subtle night-to-night changes in sleep in a sample of the general population predict consequential day-to-day changes in pain (bidirectionally). Considering the societal rise in chronic pain conditions in lock-step with the decline in sleep time through the industrial world, our data support the hypothesis that these two trends may not simply be co-occurring but are significantly inter-related.
Learn More >The U.S. Advisory Committee on Immunization Practices recently developed recommendations for use of a new recombinant zoster vaccine (RZV).
Learn More >Gender disparities in chronic pain are well documented in the literature. However, little is known regarding the relationship between physical activity (PA) and gender disparities in chronic pain. This study described gender differences in prevalence of chronic pain and PA, and identified a type of leisure time PA that individuals frequently chose in a nationally representative sample of US adults ( = 14,449). Data from the National Health Nutrition Examination Survey 1999⁻2004 were analyzed. Individuals were categorized into no chronic pain (NCP), localized chronic pain (LCP), and widespread chronic pain (WCP) groups based on responses to a pain questionnaire. A self-report PA questionnaire was used to estimate the time spent in different types of PA. Women showed higher prevalence of LCP and WCP compared to men. Men spent more hours per week for leisure time PA compared to women, but men and women showed similar prevalence of sufficient PA to meet a PA recommendation (≥150 min/week of moderate-to-vigorous intensity PA) across chronic pain categories. However, the prevalence of sufficient PA was substantially higher among men and women with NCP compared to men and women with LCP and WCP. Additionally, both men and women chose walking as the primary type of leisure time PA. Together, gender disparities exist in the prevalence of chronic pain and hours spent for leisure time PA. More research is needed to explore the role of increasing leisure time PA, such as walking, in reducing gender disparities in chronic pain.
Learn More >Complex regional pain syndrome (CRPS) is a debilitating condition where trauma to a limb results in devastating persistent pain that is disproportionate to the initial injury. The pathophysiology of CRPS remains unknown; however, accumulating evidence suggests it is an immunoneurological disorder, especially in light of evidence of auto-antibodies in ~ 30% of patients. Despite this, a systematic assessment of all circulating leukocyte populations in CRPS has never been performed.
Learn More >Self-management interventions are well recognised and widely used in chronic conditions. Their application to chronic headaches has been limited and generally of low quality. We describe here our process for developing an evidence based, and theory driven, education and self-management intervention for those living with chronic headache.
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