Pain
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The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg(-1)·d(-1), orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. ⋯ In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics.
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Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. ⋯ In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.
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Number-based assessment tools are used to evaluate pain perception in patients and determine the effect of pain management. The aim of this study was to determine the ability of chronic and acute pain patients to score their response to randomly applied noxious stimuli and assess the effect of opioid treatment. Thirty-seven healthy controls, 30 fibromyalgia patients, and 62 postoperative patients with acute pain received random heat pain (Hp) and electrical pain (Ep) stimuli. ⋯ The data were analyzed using a penalty score system, based on the assumption that stimuli of higher intensity are scored with a greater NRS, and stratified into cohorts corresponding to "good," "mediocre," and "poor" scoring. Healthy controls were well able to score pain with 73% (Hp) and 81% (Ep) of subjects classified into cohort "good." Fibromyalgia had a negative effect on scoring with 45% (Hp, P = 0.03 vs controls) and 67% (Ep) of patients in cohort "good." In controls, scoring deteriorated during opioid administration leaving just 40% (Hp, P = 0.015 vs baseline) and 70% (Ep) of subjects in the cohort "good." Similar observations were made in fibromyalgia patients (P = 0.02) but not in surgical patients with postoperative pain. Consistency to grade pain using an NRS is high in healthy volunteers but deteriorates in chronic pain and during opioid administration to volunteers and chronic pain patients but not to acute pain patients.
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Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1. ⋯ Systemic or intrathalamic delivery of Z944 to rats with CCI normalized these changes. Systemic Z944 also reversed thermal hyperalgesia and conditioned place preference. These data suggest that pain-induced cortical synchrony and thalamocortical disconnectivity are directly related to burst firing in VPL.
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Randomized Controlled Trial
A randomized, phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain.
Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after bunionectomy. ⋯ TRV130 at 2 and 3 mg produced significantly greater categorical pain relief than morphine (P < 0.005) after the first dose, with meaningful pain relief occurring in under 5 minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. These results demonstrate that TRV130 rapidly produces profound analgesia in moderate-to-severe acute pain, suggesting that G-protein-biased μ-opioid receptor activation is a promising target for development of novel analgesics.