Pain
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We describe an animal model of nociceptive sensory neuropathy induced by repeat intravenous administration of oxaliplatin in which treated animals partly reproduce the characteristic pain symptoms in oxaliplatin-treated patients. We tested the ability of 1, 2 and 4 mg/kg oxaliplatin doses injected twice-weekly for four-and-a-half consecutive weeks to induce a nociceptive peripheral neuropathy in male Sprague-Dawley rats. ⋯ The 2mg/kg oxaliplatin dose and the tail-immersion test in cold water (10 degrees C) were selected to compare pharmacological sensitivity between single administered drugs as morphine, lidocaine, carbamazepine, gabapentin and repeated administration of drugs as clomipramine, venlafaxine, calcium and magnesium solutions. Magnesium solution (90 mg/kg) and venlafaxine (7.5 mg/kg) administration induced an antinociceptive effect whereas gabapentin (300 mg/kg), clomipramine (2.5 mg/kg) and lidocaine (3 and 6 mg/kg) only induced an antiallodynic effect.
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Intra-articular injection of mono-iodoacetate (MIA) in the rat knee joint induces a histopathology with similarities to osteoarthritis (OA). Typically, a synovitis (days 1-3) is observed followed by thinning of articular cartilage and subsequent lesion of subchondral bone at days 8-14 onwards. Behaviourally, weight-bearing asymmetry is observed, which is sensitive to anti-inflammatory pharmacology at early but not later (days 14+) time points. ⋯ Significant resolution of weight-bearing was observed at high and intermediate doses of amitriptyline and gabapentin at all time points (P<0.05, ANOVA, post-hoc Bonferroni's, vs pre-dose measurements). Transient and weak effects were observed with naproxen (10mg/kg) on days 14 and 28, whereas celecoxib showed no significant effects. Collectively, these data suggest that this putative model of OA is associated with an early phase neuropathy in the L5 innervation territory of the knee.
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Comparative Study
Defining the nociceptive flexion reflex (NFR) threshold in human participants: a comparison of different scoring criteria.
Despite the widespread use of the nociceptive flexion reflex (NFR) paradigm in clinical and experimental pain research, there is currently no consensus on how best to define NFR threshold. Accordingly, the present studies were designed to assess the accuracy and reliability of different NFR threshold scoring criteria. Study 1 compared 13 scoring criteria in their accuracy for identifying the presence of the NFR, then generated empirically derived cut-points for the best criteria, and examined the test-retest reliability of NFR thresholds derived from these cut-points. ⋯ Results from the two studies suggested that standardized peak (NFR Interval Peak z score) and mean (NFR Interval z score) biceps femoris electromyogram (EMG) activity were accurate and reliable criteria for defining NFR threshold. Acknowledging that cut-points may need to be adjusted for different research designs, graphs depicting sensitivity and specificity across a range of cut-points have been provided to facilitate researcher's decision-making. It is hoped that the results of these studies will promote a standard NFR threshold assessment methodology, and further encourage the application of the NFR paradigm in the investigation of mechanisms and characteristics of both painful and non-painful diseases.
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Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. ⋯ There was a weak, but significant positive correlation between SP levels and ACE activities (P<0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.