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Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or prior experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo response in chronic low back pain using over 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not treated). Utilizing a nested leave-one-out cross-validated approach, we distinguished placebo responders from non-responders with 79% accuracy using language features alone; a subset of these features – semantic distances to identity and stigma and the number of achievement-related words – also explained 46% of the variance in placebo analgesia. Importantly, these language features were not due to generic treatment effects and were associated with patients' specific baseline psychological traits previously shown to be predictive of placebo including awareness and personality characteristics, explaining an additional 31% of the variance in placebo analgesia beyond that of personality. Initial interpretation of the features suggests that placebo responders differed in how they talked about negative emotions and the extent that they expressed awareness to various aspects of their experiences; differences were also seen in time spent talking about leisure activities. These results indicate that patients' language is sufficient to identify placebo response and implies that specific speech features may be predictive of responders prior to treatment.
Learn More >Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 as important aging-related protein with function of lifespan extension, whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. Following nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents while increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenile rodents. Furthermore, SIRT1 interacted with ClC-3 channel and mediated ClC-3 membrane trafficking and Cl¯ current in DRG neurons. Differential manipulation of ClC-3 also abolished the difference in pain vulnerability between adult and juvenile rodents. The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with pain score in chronic pain patients. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.
Learn More >Migraine is a cyclic disorder but also a chronic pain condition. Left-right recognition tasks have been shown to be impaired in patients with chronic pain.
Learn More >Pain and depression are episodic conditions that might take a chronic course. They are clearly related, but information on how they influence each other in the process of chronification is limited. Pain catastrophizing is hypothesized to play a role in the development of depression and chronic pain, but few longitudinal studies have investigated their association over a longer-term. In this study, a random cohort from the general population (n = 4764) answered questions about pain, catastrophizing, and depression at five assessments in yearly intervals. Linear mixed models showed that within persons, increases in pain intensity and catastrophizing were independently associated with increases in depressive symptoms (mean change = -1.12, 95% CI [-1.32, -0.91]) and -1.29, 95% CI [-1.52, -1.05], respectively). In prospective analyses restricted to individuals without depression above cut-off at baseline, chronic pain increased the risk of endorsing depression over the following four years (OR =2.01, 95% CI [1.71, 2.37]). Seven percent showed a chronic course of depression, as indicated by scores above cut-off on at least three of five assessments. Number of years lived with chronic pain was associated with a chronic course of depression, with odds ratios increasing from 1.55 (95% CI [0.87, 2.91]) to 14.19 (95% CI [8.99, 22.41]) when reporting chronic pain on two versus five assessments compared to none. The results suggest that when pain intensity or catastrophizing change, depressive symptoms change in the same direction. When pain and catastrophizing become chronic, they appear to be mutually reinforcing determinants for chronic depression.
Learn More >To evaluate the effect of erenumab on patient-reported, functional outcomes in patients with episodic migraine (EM) in whom 2-4 preventives were not useful from the Phase 3b LIBERTY study.
Learn More >To determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine.
Learn More >Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.
Learn More >Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate-induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.
Learn More >Biased interpretations of ambiguous bodily threat situations characterise youth with chronic pain, and have been associated with functional disability for this population. Despite predictions by the fear-avoidance model of chronic pain, that fear and avoidance of pain explain the association between threat perceptions and disability, this has not yet been explored in youth with chronic pain. The current study aimed to address this gap by investigating these proposed relationships, in addition to the association between bodily threat interpretations and daily aspects of disability (as well as social, and emotional impairments).
Learn More >Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3-12 months, little is known about long-term therapy.
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