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To develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy-based, internet-delivered self-management program for chronic low back pain (cLBP) in veterans.
Learn More >Opioids are prescribed to manage moderate to severe pain and can be used with older adults; however, they may lead to several adverse effects, including cognitive impairment.
Learn More >Neuropathic pain correlates with a lesion or other dysfunction in the nervous system. Sphingosine-1-phosphate receptor 2 (S1P2) is expressed in the central nervous system and modulates synaptic plasticity. The present study aimed to investigate the role of S1P2 in neuropathic pain caused by chronic constriction injury (CCI). Sprague-Dawley rats were allocated into eight groups (n = 15 for each group): sham, CCI, CCI + green fluorescent protein, CCI + S1P2, CCI + Ctrl-short hairpin RNA (shRNA), CCI + S1P2 shRNA, CCI + S1P2 + CYM-5442, and CCI + S1P2 shRNA + CYM-5442. The CCI model was established via sciatic nerve ligation. S1P2 was overexpressed or knocked down by intrathecal injection of adeno-associated virus-S1P2 (AAV-S1P2) or AAV-S1P2 shRNA. The S1P1 agonist, CYM-5442 (1 mg/kg), was injected intraperitoneally after surgery. S1P2 expression, pain thresholds, apoptosis signaling, inflammation, and oxidative stress in rats were then examined. We found that sciatic nerve injury downregulated S1P2 expression in the spinal cords of rats. S1P2 overexpression enhanced pain thresholds. In contrast, S1P2 knockdown decreased pain thresholds in rats exposed to CCI. CCI and S1P2 silencing increased secretion of interleukin-1β (IL-1β), IL-6, and CCL2, whereas S1P2 overexpression decreased. S1P2 impeded CCI-induced reactive oxygen species (ROS) production and runt-related transcription factors 3 (RUNX3) downregulation, and S1P2 knockdown had the opposite effect. S1P2 overexpression suppressed Bax and active caspase 3 expression and promoted Bcl-2 expression, whereas loss of S1P2 reversed their expression. Additionally, S1P1 activation counteracted the effect of S1P2 on pain sensitivity. In conclusion, S1P2 is downregulated in CCI rats and may help modulate neuropathic pain via the ROS/RUNX3 pathway.
Learn More >This study investigated 1) if a prolonged noxious stimulus (24-hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and 2) if acute pain relief or exacerbation (cooling and heating the capsaicin patch) during the prolonged noxious stimulus would affect central pain modulation.
Learn More >Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain-meninges-bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response. Accordingly, this study examines the upregulation of an inflammatory marker in extra-axial tissues in migraine with visual aura.
Learn More >Pinprick evoked potentials (PEPs) represent a novel tool to assess the functional integrity of mechano-nociceptive pathways with a potential toward objectifying sensory deficits and gain seen in neurological disorders. The aim of the present study was to evaluate the feasibility and reliability of PEPs with respect to age, stimulation site, and skin type.
Learn More >Painful diabetic peripheral neuropathy (PDPN) is a chronic pain condition with modest response to pharmacotherapy. Participation in mindfulness-based stress reduction (MBSR) leads to improvements in pain-related outcomes but the mechanisms of change are unknown. The present study examined the mediators and moderators of change in 62 patients with PDPN who participated in a randomized controlled trial comparing MBSR to waitlist. Changes in mindfulness and pain catastrophizing were tested simultaneously as mediators. Increased mindfulness mediated the association between participation in MBSR and improved pain severity, pain interference, and the physical component of health-related quality of life (HRQoL) 3 months later. The mediation effect of pain catastrophizing was not significant. Linear moderated trends were also found. Post-hoc moderated mediation analyses suggested that MBSR patients with longer histories of diabetes might increase their mindfulness levels more, which in turn leads to improved pain severity and physical HRQoL. These results allow for a deeper understanding of pathways by which MBSR benefits patients with PDPN.
Learn More >Opioids are the recommended form of analgesia for patients with persistent cancer pain and regular dosing 'by the clock' is advocated in many international guidelines on cancer pain management. The development of sustained release opioid preparations has made regular dosing easier for patients. However, patients report that the intensity and impact of their cancer pain varies considerably day to day, and many try to find a trade-off between acceptable pain control and impact of cognitive (and other) adverse effects on daily activities. In acute care settings, (eg post-operative) as needed dosing and other opioid sparing approaches have resulted in better patient outcomes compared with regular dosing. The aim of this study was to determine whether regular dosing of opioids was superior to as needed dosing for persistent cancer pain. We systematically searched for randomised controlled trials that directly compared pain outcomes from regular dosing of opioids with as needed dosing in adult cancer patients. We identified 4347 records, 25 RCTs meet the inclusion criteria, nine were included in the review and 7 of these included in meta-analysis. We found no clear evidence demonstrating superiority of regular dosing of opioids compared with as needed dosing in persistent cancer pain and regular dosing was associated with significantly higher total opioid doses. There was, however, a paucity of trials directly answering this question and low-quality evidence limits the conclusions that can be drawn. It is clear that further high-quality clinical trials are needed to answer this question and to guide clinical practice.
Learn More >Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients' quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.
Learn More >Disturbances in the function of the mesostriatal dopamine system may contribute to the development and maintenance of chronic pain, including its sensory and emotional/cognitive aspects. In the present study, we assessed the influence of chronic constriction injury (CCI) of the sciatic nerve on the expression of genes coding for dopamine and opioid receptors as well as opioid propeptides in the mouse mesostriatal system, particularly in the nucleus accumbens. We demonstrated bilateral increases in mRNA levels of the dopamine D1 and D2 receptors (the latter accompanied by elevated protein level), opioid propeptides proenkephalin and prodynorphin, as well as delta and kappa (but not mu) opioid receptors in the nucleus accumbens at 7 to 14 days after CCI. These results show that CCI-induced neuropathic pain is accompanied by a major transcriptional dysregulation of molecules involved in dopaminergic and opioidergic signaling in the striatum/nucleus accumbens. Possible functional consequences of these changes include opposite effects of upregulated enkephalin/delta opioid receptor signaling vs. dynorphin/kappa opioid receptor signaling, with the former most likely having an analgesic effect and the latter exacerbating pain and contributing to pain-related negative emotional states.
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