Pain
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Randomized Controlled Trial Multicenter Study
Paracetamol is ineffective for acute low back pain even for patients who comply with treatment: complier average causal effect analysis of a randomized controlled trial.
In 2014, the Paracetamol for Acute Low Back Pain (PACE) trial demonstrated that paracetamol had no effect compared with placebo in acute low back pain (LBP). However, noncompliance was a potential limitation of this trial. The aim of this study was to investigate the efficacy of paracetamol in acute LBP among compliers. ⋯ Mean between-group differences in pain intensity on a 0 to 10 scale using the primary time point and definition of compliance were not clinically relevant (propensity-weighted CACE 0.07 [-0.37 to 0.50] P = 0.76; joint modelling CACE 0.23 [-0.16 to 0.62] P = 0.24; intention-to-treat 0.11 [-0.20 to 0.42] P = 0.49; per protocol 0.29 [-0.07 to 0.65] P = 0.12); results for secondary outcomes and for exploratory analyses were similar. Paracetamol is ineffective for acute LBP even for patients who comply with treatment. This reinforces the notion that management of acute LBP should focus on providing patients advice and reassurance without the addition of paracetamol.
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Randomized Controlled Trial
A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery.
Endogenous opioid peptides and exogenous opioids modulate immune function, and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance, eg, in cancer patients and surgery. The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients. ⋯ At 2 hours, a large number of genes were downregulated with morphine but not with control analgesia or oxycodone. Statistically significant increases in IL-6 concentrations were induced by morphine only; NK cell activity was suppressed with morphine, but maintained with oxycodone and epidural analgesia. Gene expression profiles suggest that at 2 hours, post incision morphine appeared to be immunosuppressive as compared to oxycodone and nonopioid control analgesia.
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As well established for patients with chronic pain, patients suffering from chronic itch also exhibit signs of peripheral and central sensitization. This has been linked to parallel neuroplastic sensitization processes. However, for chronic itch, sensitization has not yet been systematically assessed, studied, and hence validated. ⋯ For numerous other chemical provocations as well as for mechanical, thermal, and electrical stimulation paradigms, results were ambiguous or based on few studies. Patients with chronic itch are only robustly sensitized to various chemical pruritic stimuli when applied lesionally. More studies on somatosensory aberrations in chronic itch conditions other than AD are needed to establish whether sensitization is robustly present across chronic itch conditions.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of cancer treatment with no Food and Drug Administration-approved medication for its prevention or management. Using RNA sequencing analysis of dorsal root ganglia (DRG), we identify critical contributions of histone deacetylase 6 (HDAC6) and mitochondrial damage to the establishment of CIPN in a mouse model of cisplatin-induced neuropathy. We show that pharmacological inhibition of HDAC6 using ACY-1215 or global deletion of HDAC6 is sufficient to prevent cisplatin-induced mechanical allodynia, loss of intraepidermal nerve fibers (IENFs), and mitochondrial bioenergetic deficits in DRG neurons and peripheral nerves in male and female mice. ⋯ We further reveal a critical role of T cells in the protective effects of HDAC6 inhibition on these signs of CIPN. In summary, we show that cisplatin-induced mechanical allodynia is associated with mitochondrial damage in DRG neurons, whereas the loss of IENFs is related to bioenergetic deficits in peripheral nerves. Moreover, our findings identify cell-specific contributions of HDAC6 to mechanical allodynia and loss of IENFs that characterize cisplatin-induced peripheral neuropathy.
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Randomized Controlled Trial
Effects of open-label placebo on pain, functional disability and spine mobility in chronic back pain patients: a randomized controlled trial.
Chronic back pain (CBP) is a major global health problem, while its treatment is hampered by a lack of efficacy and restricted safety profile of common frontline therapies. The present trial aims to determine whether a 3-week open-label placebo treatment reduces pain intensity and subjective and objective functional disability in patients with CBP. This randomized controlled trial, following a pretest-posttest design, enrolled 127 patients with CBP (pain duration >12 weeks) from the Back Pain Center, Neurology, University Hospital Essen, Germany. ⋯ Open-label placebo treatment did not affect objective mobility parameters, anxiety and stress. Our study demonstrates that a 3-week open-label placebo treatment is safe, well tolerated and reduces pain, disability, and depressive symptoms in CBP. Trial registration: German Clinical Trials Register, DRKS00012712.