Browse by Audience
There exists a limited number of studies investigating the correlation between spinal adenosine A1 receptors and Vincristine-induced peripheral neuropathy (VIPN). This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in neuropathic pain induced in rats by administering vincristine (100 μg/kg i.p.) for 10 days (two 5-day cycles with a 2-day pause).
Learn More >Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such phenomenon are unclear. Here we investigate how threat predictions generated from learning a cognitive schema leads to inaccurate sensory impressions of the pain stimulus. Healthy men and women participants first detected a linear association between cue-values and stimulus intensity and rated pain to reflect the linear schema when compared with un-cued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors increased, but pain perception was only partially updated when measured against stepped increases in prediction errors. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite of the prediction errors (p<0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventral medial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas on pain perception and indicates that pain perception is biased more towards predictions and less towards nociceptive inputs in individuals who report less mindfulness and more fear of pain.Significance statement: This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite of increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation with the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum respectively. These findings direct us to a significant role of top-down processes in pain perception.
Learn More >There is substantial evidence that pain intensity and sleep are related, with findings generally suggesting more support for the influence of sleep on pain intensity than vice versa. However, the strength and direction of the relationship has been found to vary among different populations, with few studies in individuals with chronic physical disabilities.
Learn More >This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n=142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single center, double blind, 12-week, four-arm, parallel groups controlled clinical trial of: 1) low concentration desipramine titrated to reach a serum concentration level of 15-65 ng/ml; 2) CBT and active placebo medication (benzotropine mesylate, 0.125mg); 3) low concentration desipramine and CBT; and 4) active benztropine placebo medication. Participants completed the Differential Description Scale and Roland-Morris Disability Questionnaires pre and post-treatment as validated measures of outcomes in back pain intensity and disability, respectively. Participants within each condition showed significant reductions from pre to post-treatment in pain intensity (mean changes ranged from = -2.58-3.87, Cohen's d's = 0.46-0.84) and improvements in pain disability (mean changes = -3.04-4.29, Cohen's d's = 0.54-0.88). However, intent-to-treat analyses at post-treatment showed no significant differences between any condition, with small effect sizes ranging from .06-.27. The results from this clinical trial did not support the hypothesis that desipramine, CBT, or their combination would be statistically superior to an active medicine placebo for reducing chronic back pain intensity or disability. Key limitations included recruiting 71% of the planned sample size and use of multiple inclusion/exclusion criteria that may limit generalizability to broader populations of patients with chronic back pain.
Learn More >Cancer-induced pain (CIP) is a kind of chronic pain that occurs during cancer progression over time. However, the mechanisms are largely unknown, and clinical treatment remains challenging. LncRNAs have been reported to play critical roles in various biological processes, including chronic pain. The aim of our study was to investigate whether lncRNAs participate in the development of CIP by regulating the expression levels of some molecules related to pain modulation. The CIP model was established by injecting Walker 256 mammary gland tumor cells into the tibial canal of rats. In this study, we found that lncRNA-NONRATT021203.2 was increased in the CIP rats and that lncRNA-NONRATT021203.2-siRNA could relieve hyperalgesia in these rats. For elucidation of the underlying mechanism, we showed that lncRNA-NONRATT021203.2 could target C-X-C motif chemokine ligand 9 (CXCL9), which was increased in the CIP rats, and that CXCL9-siRNA could relieve hyperalgesia. At the same time, silencing lncRNA-NONRATT021203.2 expression decreased the mRNA and protein levels of CXCL9. Immunofluorescence analysis showed that CXCL9 was mainly expressed in the CGRP-positive and IB4-positive DRG neurons. Further research showed that lncRNA-NONRATT021203.2 and CXCL9 were colocalized in the DRG neurons. Our data suggested that lncRNA-NONRATT021203.2 participated in the CIP in rats and likely mediates the upregulation of CXCL9. The present study provided us with a new potential target for the clinical treatment of cancer-induced pain.
Learn More >Although many patients with cluster headaches (CH) are disabled by their condition, few studies have examined this in detail. This cross-sectional, multicenter observational study prospectively collected demographic and clinical questionnaire data from 224 consecutive patients with CH. We assessed headache impact using the six-item Headache Impact Test (HIT-6) and evaluated the factors associated with the impact of CH. Participants with a HIT-6 score ≥ 60 were classified into a severe impact group. The majority (190, 84.8%) of the participants were classified into the severe impact group. These patients were characterized by younger age, earlier onset of CH, longer duration of each headache attack, higher pain intensity, more cranial autonomic symptoms, a higher proportion of depression or anxiety, higher score of stress, and lower score of quality of life. The anxiety (OR = 1.19, 95% CI: 1.08-1.31, p = 0.006), greater pain intensity (OR = 1.06, 95% CI: 1.02-1.10, p = 0.002), and age (OR = 0.99, 95% CI: 0.99-1.00, p = 0.008) were significant predictors for a severe impact of CH patients. According to the HIT-6 results, most of the CH patients were significantly affected by CH. As well as pain intensity, anxiety and age modulated CH's impact on their lives.
Learn More >: Document headache presence, intensity, and interference after concussion(s), as well as examine its association with cognition.: Participants 8-19 years of age were assessed on average 34 months ( = 21.5) after an orthopedic injury (OI, = 29), single concussion ( = 21), or multiple concussions ( = 15).: Headache intensity was rated using the Headache Rating Scale and headache interference was rated using the Post-Concussion Symptom Inventory (PCSI). Cognition was rated using the PCSI and measured using CNS Vital Signs.: Type of injury did not differ significantly in headache presence or intensity. However, there was a dose-response relationship found for children's ratings of headache interference, which was rated highest among children with multiple concussions, intermediate among those with single concussion, and lowest among children with OI. Both headache intensity and interference ratings correlated significantly with self and parent ratings of cognition on the PCSI, but not with cognitive test performance.: Youth with single or multiple concussions report greater headache interference – but not higher headache intensity – compared to youth without concussion. Although higher headache intensity and interference were associated with more self-reported cognitive symptoms, headaches did not correlate with cognitive test performance.
Learn More >G protein-coupled receptors can signal through both G proteins and ß-arrestin2. For the μ-opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia whereas ß-arrestin2 signalling mediates respiratory depression and constipation. Consequently, for more than a decade much research effort has been focused on developing biased μ-opioid agonists that preferentially target G protein signalling over β-arrestin signalling as it was believed that such drugs would be analgesics devoid of respiratory depressant activity. However, the prototypical compounds that have been developed based on this concept have so far failed in clinical and preclinical development.
Learn More >Almost one-quarter of Asian patients with diabetes experience diabetic peripheral neuropathic pain (DPNP), which may be associated with moderate or severe levels of pain, insomnia, mood disorders, and worsened quality of life. Current treatments are generally ineffective and may be poorly tolerated. We evaluated mirogabalin as a treatment for DPNP in Asian subjects.
Learn More >Musculoskeletal (MSK) pain is the primary contributor to disability worldwide. There is a growing consensus that MSK pain is a recurrent multifactorial condition underpinned by health and lifestyle factors. Studies suggest that education on work-related pain and individualised advice could be essential and effective for managing persistent MSK pain.
Learn More >