Articles: neuropathic-pain.
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Randomized Controlled Trial
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial.
In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. ⋯ No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
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High molecular weight hyaluronan (HMWH) inhibits hyperalgesia induced by diverse pronociceptive inflammatory mediators and their second messengers, in rats of both sexes. However, the hyperalgesia induced by ligands at 3 pattern recognition receptors, lipopolysaccharide (a toll-like receptor 4 agonist), lipoteichoic acid (a toll-like receptor 2/6 agonist), and nigericin (a NOD-like receptor family, pyrin domain containing 3 activator), and oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy are only attenuated in males. After gonadectomy or intrathecal administration of an antisense to G-protein-coupled estrogen receptor 30 (GPER) mRNA, HMWH produces antihyperalgesia in females. ⋯ In females, hyperalgesia induced by PKCε agonist, ψεRACK, in control but not in primed nociceptors, was inhibited by HMWH. Inhibitors of 2 GPER second messengers, extracellular-regulated kinase 1/2 and nonreceptor tyrosine kinase, also unmasked HMWH antihyperalgesia in females with oxaliplatin chemotherapy-induced peripheral neuropathy, a condition in which nociceptors are primed as well as sensitized. Our results support GPER-dependent sex dimorphism in HMWH-induced antihyperalgesia for pain induced by pattern recognition receptor agonists, and chronic inflammatory and neuropathic pain, mediated by changes in signaling downstream of PKCε in primed nociceptors.
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Neuropathic pain is pain due to a disease or lesion of the somatosensory system, and can be either spontaneous, evoked or both. Hyperpathia is a type of evoked pain defined by IASP as 'a painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold'. The literature is sparse, and definitions are unclear and inconsistent. ⋯ Hyperpathia is a syndrome of evoked pain. It is poorly defined and little is known about its clinical presentation. Since it is part of pain symptomatology it is important to have a clear definition and understand the pathophysiology behind. This study explored signs of hyperpathia in a heterogeneous group of patients with peripheral neuropathic pain. We used stimulus-response function and repetitive pinprick stimulation to group patients based on the IASP definition. More studies are needed to understand how symptoms and signs coincide.
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This study explored surface brain morphometry in type 1 diabetes including focus on painful diabetic peripheral neuropathy (DPN). Brain MRI was obtained from 56 individuals with diabetes (18 without DPN, 19 with painless DPN, 19 with painful DPN) and 20 healthy controls. Cortical thickness, sulcus depth, and gyrification were analysed globally and regionally in each group and in the combined diabetes group. ⋯ Cortical thinning manifested across the brain cortex in diabetes, especially for painful DPN. Altered postcentral gyrus morphometry may be associated with neuropathic pain. Assessing cortical morphometry may be critical for comprehending central neuropathy and the manifestation of painful DPN in diabetes.
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Spine-related neck-arm pain is heterogeneous and may present on a spectrum between nociceptive and neuropathic pain. A recently developed mechanism-based clinical framework for spine-related pain distinguishes between spinally referred pain without neurological deficits (somatic referred pain, heightened nerve mechanosensitivity, radicular pain), with neurological deficits (radiculopathy), and mixed-pain presentations. This study investigated differences in somatosensory and clinical profiles of patients with unilateral spine-related neck-arm pain grouped according to the clinical framework. ⋯ Symptom descriptors, such as burning (P < 0.031), tingling (P < 0.018), pins and needles (P < 0.031), numbness (P < 0.016), spontaneous pain (P < 0.001), and electric pain/shock (P < 0.026) were more common in the radicular/radiculopathy groups compared with the somatic/mechanosensitivity groups. There were no differences in psychosocial parameters between the groups. The phenotypic profiles support the construct of the clinical examination and patient classification and its application in clinical practice according to a clinical framework for spine-related pain.