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Diagnostic utility of small fiber analysis in skin biopsies from children with chronic pain.

Small fiber neuropathies (SFN) are associated with a reduction in quality of life. In adults, epidermal nerve fiber density (END) analysis is recommended for the diagnosis of SFN. In children, END assessment is not often performed. We analyzed small nerve fiber innervation to elucidate the potential diagnostic role of skin biopsies in young patients with pain.

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Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain: preplanned subgroup analyses of the multicenter randomized PANSAID trial.

The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.

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Cannabinoid effects on responses to quantitative sensory testing among individuals with and without clinical pain: a systematic review.

There has been an explosion of interest in the utility of cannabinoids as potential analgesics. This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic non-cancer pain (CNCP). Our systematic review protocol is pre-registered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1,217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for the present study. Due to substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted. More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids. Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with CNCP. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.

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Effects of chronic pain history on perceptual and cognitive inhibition.

Measures of sensory and cognitive inhibition were obtained from university students with and without a history of chronic pain. The form of sensory inhibition measured was diffuse noxious inhibitory controls (DNIC), the capacity of a painful stimulus to reduce the subjective intensity of a second stimulus delivered to a remote body site. To measure cognitive inhibition, the Stroop effect was used. Participants with a history of chronic pain showed less DNIC (i.e., less sensory inhibition) than the healthy controls, but had a smaller Stroop effect (indicating greater cognitive inhibition). The fact that chronic pain history is associated with opposite changes in these two measures casts doubt on the view that the two inhibitory processes are related. Scores on each experimental measure were equivalent in pain-history subjects with ongoing chronic pain and those whose chronic pain had resolved. This equivalence suggests that chronic pain in childhood or adolescence may have lingering effects on sensory and cognitive inhibition.

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Identification of the cerebral effects of paracetamol in healthy subjects: an fMRI study.

Paracetamol is commonly used for its antipyretic properties and analgesic effects, but the central mechanism remains elusive. We designed a study in healthy volunteers to detect the central functional working mechanism of paracetamol.

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Histamine, histamine receptors and neuropathic pain relief.

Histamine, acting via distinct histamine H , H , H and H receptors (H R, H R, H R, H R), regulates various physiological and pathological processes, including pain. In the last two decades, there has been a particular increase in evidence to support the involvement of H R and H R in the modulation of neuropathic pain, that remains challenging in terms of management. However, recent data show contrasting effects on neuropathic pain due to multiple factors that determine the pharmacological responses of histamine receptors and their underlying signal transduction properties (e.g., localization on either the pre- or postsynaptic neuronal membrane). This review summarizes the most recent findings on the role of histamine and the effects mediated by the four histamine receptors in response to the various stimuli associated with and promoting neuropathic pain. We particularly focus on mechanisms underlying histamine-mediated analgesia, as we aim to clarify the analgesic potential of histamine receptor ligands in neuropathic pain.

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A QST-based Pain Phenotype in Adults with Sickle Cell Disease: Sensitivity and Specificity of Quality Descriptors.

We sought to refine a screening measure for discriminating a sensitized or normal sensation pain phenotype among African American adults with sickle cell disease (SCD).

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Small-fiber neuropathy and pruritus: histological patterns of nerve fibers in skin biopsies.

Small fiber neuropathy (SFN) is a disease of intraepidermal nerves fibers (IENF) (myelinated Aδ and unmyelinated C-fibers) prevalent in about 53/100,000 people. Mostly idiopathic, SFN can have various etiologies as alcoholism, diabetes, immune-mediated or infectious diseases. SFN commonly affects limbs in a distal to proximal gradient and manifests as various sensory symptoms. The diagnosis of SFN must fulfill following criteria : 1- a symptomatology consistent with neuropathic pains and autonomic complaints; 2- no central or motor involvement; 3- no nervous trunk achievement detected on electromyogram; 4- a reduction of IENF density (IENFD) in the distal area measured on skin biopsy ("gold standard" for diagnosis). This article is protected by copyright. All rights reserved.

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Role of transient receptor potential ankyrin 1 (TRPA1) on nociception caused by a murine model of breast carcinoma.

Breast carcinoma causes severe pain, which decreases the quality of life of patients. Current treatments produce adverse effects and have limited efficacy. Transient potential receptor ankyrin 1 (TRPA1) is related to the onset of cancer and neuropathic pain. The aim of this study was to evaluate the involvement of TRPA1 in a model of breast carcinoma. We injected 4T1 cells in the fourth caudal mammary fat pad of female BALB/c mice, and after 20 days we observed mechanical and cold allodynia and spontaneous nociception behavior (mouse grimace scale detection, MGS). TRPA1 selective antagonist (HC-030031 or A-967079) administration or intrathecal administration of TRPA1 antisense (AS) oligonucleotide was performed. The activity of NADPH oxidase, superoxide dismutase (SOD) and hydrogen peroxide (HO) levels were evaluated. The chemical hyperalgesia produced by a TRPA1 agonist (allyl isothiocyanate, AITC) was also detected. The administration of TRPA1 antagonists, TRPA1 AS, or antioxidant, transiently attenuated MGS, or mechanical and cold allodynia. Intraplantar injection of AITC also caused nociception. NADPH oxidase or SOD activity and HO levels were increased in the sciatic nerve and hind paw skin samples. The 4T1 cells did not express TRPA1, and the use of HC-030031 or α-lipoic acid did not reduce the cytotoxic effect of a chemotherapeutic drug (paclitaxel). Thus, TRPA1 could be investigated as a target for breast carcinoma pain treatment.

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An exploratory investigation into the longevity of pain reduction following multisensory illusions designed to alter body perception.

Previous research suggests that multisensory body illusions that alter the conscious bodily experience can modulate pain in osteoarthritis, which may be a result of modifying cortical misrepresentations of the painful body part. However, the longevity and underlying mechanisms of such illusion-induced analgesia is unknown.

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