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Placebo treatments even if known to the patient to be placebo, so-called "open label placebo," may be effective in reducing chronic painThe effects of the extent of placebo education are poorly understood WHAT THIS ARTICLE TELLS US THAT IS NEW: Using a well-characterized electrical pain sensitization model in human volunteers, the effects of short versus detailed placebo educational protocols were measuredOpen label placebo treatment reduced pain sensitization in the volunteers, but the extent of placebo education did not modify these responses BACKGROUND:: Open label placebos with patient education are effective in reducing chronic pain, and recent studies on their effect on pain have established interest in this field. Nevertheless, data on their effect on acute pain are scarce, and on hyperalgesia and allodynia, absent. This study assessed the effect of open label placebos on acute pain in healthy adult males and the influence of placebo education.
Learn More >Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk for continued pain in adulthood. Abberations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally-appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional MRI responses (N = 72 after fMRI exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and fronto-limbic activity in response to learned threat and safety cues compared to both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus, amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant fronto-limbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by fronto-limbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.
Learn More >Chronic neuropathic pain (NP) is debilitating and impacts sleep health and quality of life. Treatment with gabapentinoids (GB) has been shown to reduce pain, but its effects on sleep health have not been systematically evaluated. The objective of this systematic review and meta-analysis was to assess the relationship between GB therapy dose and duration on sleep quality, daytime somnolence, and intensity of pain in patients with neuropathic pain. Subgroup comparisons were planned for high vs. low dose GB, where 300mg per day or more of pregabalin was used to classify high-dose therapy. Trial data was segregated by duration less than 6 weeks and 6 weeks or greater. Twenty randomized controlled trials were included. Primary outcome measures included pain-related sleep interference and incidence of daytime somnolence. Secondary outcomes included daily pain scores (NRS 0-10) and patient global impression of change (PGIC). Significant improvement in sleep quality was observed after 6 weeks of GB treatment when compared to placebo (SMD 0.39, 95% CI 0.32 to 0.46 p<.001). Increased daytime somnolence was observed among all GB-treated groups when compared to placebo. Treated patients were also more likely to report improvement of PGIC scores. Pain scores decreased significantly in patients both after 6 weeks of treatment (p<.001) and in trials less than 6 weeks (p=0.017) when compared to placebo. Our data demonstrates that GBs have a positive impact on sleep health, quality of life, and pain in patients with NP syndromes. However, these benefits come at the expense of daytime somnolence.
Learn More >Chronic pain is mainly treated with opioid analgesics such as morphine. However, the use of these substances can cause adverse effects, including dependence and tolerance, necessitating the discovery of a new approach to analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) is linked to thermal sensibility and has been considered as a new therapeutic option for pain treatment. This study aims to investigate the antinociceptive effect and toxicity of SB-366791, a TRPV1 antagonist. Morphine-tolerant and morphine non-tolerant Swiss mice were submitted to the hot plate and thermal tail flick tests. Toxicological evaluations of the genotoxic and mutagenic activities of SB-366791 were assessed using a comet assay and micronucleus test, and the Salmonella/microsome mutagenicity assay. In the hot plate test, intrathecal injection of SB-366791 or morphine resulted in significantly increased antinociception in non-tolerant mice. SB-366791 also led to an analgesic effect in the tail flick test. Tolerant mice that received SB-366791 demonstrated a central antinociceptive effect in both thermal tests. No genotoxic effects were observed in the comet assay and no mutagenic effects were detected in the micronucleus test or in the Salmonella/microsome assay. Behavioral results of the thermal nociception tests show that SB-366791 has antinociceptive potential in both morphine-tolerant and non-tolerant mice and does not cause genotoxic or mutagenic effects. Nevertheless, new studies should be performed to clarify the activity and participation of vanilloid channels in the antinociception of SB-366791.
Learn More >To compare the effectiveness of an integrated rehabilitation programme with an existing rehabilitation programme in patients with chronic low back pain.
Learn More >Orexin-A is known to induce anti-nociceptive effects in animal models of chronic pain. We have found that orexin-A inhibits KCl loading-induced increases in the intracellular calcium ion levels ([Ca ] ) in C-fiber-like neurons of rats showing inflammatory nociceptive behavior. Here, we examined the effects of orexin-A on the depolarization of C-fiber-like neurons derived from a rat model for another type of chronic pain, namely neuropathic pain. Thus, we analyzed the effects of orexin-A on KCl-induced increases in [Ca ] in C-fiber-like neurons of rats with sciatic nerve ligation.
Learn More >When evaluating sensory dysfunctions and pain mechanisms in patients with low back pain (LBP), a specific subgroup of patients with radicular symptoms is often excluded. Comparative studies that evaluate sensory sensitivity in patients with a dominant nociceptive and neuropathic pain component are rarely performed. Therefore, the goal of this study was to examine differences in electrical thresholds and conditioned pain modulation (CPM) between patients with low back-related leg pain (LBRLP) and patients with failed back surgery syndrome (FBSS).
Learn More >Schwannomatosis and neurofibromatosis type 2 (NF2) are two distinct neuro-genetic tumor predisposition disorders which however share some clinical and genetic features. While germline mutations in the NF2 gene are only found in NF2, a majority of schwannomatosis patients have germline mutations in the SMARCB1 or LZTR1 genes. The overlapping clinical phenotypes pose a serious challenge in differential diagnosis and in risk stratification of these two entities which is further complicated by frequent mosaicism in both disorders. Chronic neuropathic pain which is a typical consequence of small fiber neuropathy, is characteristic for schwannomatosis. By contrast, NF2 patients do not have chronic pain but may have moderate to severe sensory deficits and paresis which are not characteristic for schwannomatosis. In the present study, we determined intra-epidermal nerve fiber density (IEND) in skin biopsies of 34 clinically ascertained schwannomatosis and 25 NF2 patients. In the NF2 group, 11/25 (44%) presented with IEND below the age- and gender-matched bottom 5% normative reference IEND. In contrast, nearly all (33/34=97%) schwannomatosis patients showed IEND below or on the bottom 5% normative reference. The reduction of IEND in schwannomatosis patients was age-independent. Paired t-test revealed no difference between the NF2-IEND and the corresponding bottom 5% normative reference (P=0.98). By contrast, IEND in the schwannomatosis patients were highly significantly lower than the corresponding 5% normative reference IEND (P<0.0001). In addition, the difference between the IEND of our patients and the 5% lowest normative reference IEND was highly significantly larger in schwannomatosis patients than in NF2 patients (P<0.0001). IEND of our patients did not correlate with neither the presence nor types of germline mutations in neither the NF2 nor the LZTR1 gene. In conclusion, schwannomatosis patients have marked low IEND which provides a major parameter for diagnosis and differential diagnosis. This article is protected by copyright. All rights reserved.
Learn More >We investigated the influence of sleeplessness and number of insomnia symptoms on the probability of recovery from chronic low back pain (LBP), and the possible interplay between sleeplessness and co-occurring musculoskeletal pain on this association.
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