European journal of pain : EJP
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Pathological pain states are often associated with neuronal hyperexcitability in the spinal cord. Reducing this excitability could theoretically be achieved by amplifying the existing spinal inhibitory control mediated by GABAA receptors (GABAARs). In this study, we used the non-benzodiazepine anxiolytic etifoxine (EFX) to characterize its interest as pain killer and spinal mechanisms of action. EFX potentiates GABAAR function but can also increase its function by stimulating the local synthesis of 3α-reduced neurosteroids (3αNS), the most potent endogenous modulators of this receptor. ⋯ This preclinical study shows that stimulating the production of endogenous analgesics such as 3αNS represents an interesting strategy to reduce neuropathic pain symptoms. Since EFX is already prescribed as an anxiolytic in several countries, a translation to the human clinic needs to be rapidly evaluated.
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Burrowing is an evolutionarily conserved behaviour in rodents. This study validates a refined burrowing paradigm (requiring a reduced number of animals) in a rat model of sub-chronic knee joint inflammation and evaluates its sensitivity and specificity for analgesic drugs. ⋯ This study provides pharmacological validation of a refined burrowing paradigm for analgesic efficacy that exhibits good predictive validity, with high sensitivity and specificity.
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Randomized Controlled Trial
Tropisetron alleviate early post-operative pain after gynecological laparoscopy in sevoflurane based general anaesthesia: A randomized, parallel-group, factorial study.
Studies have suggested that 5-hydroxytryptamine-3A (5-HT-3A) receptor antagonists may have analgesic effects. This randomized, double-blind, placebo-controlled, factorial study tested the hypothesis that 5-HT-3A receptor antagonist tropisetron attenuates post-operative pain in women receiving either sevoflurane or propofol based anaesthesia. ⋯ A single-dose intravenous administration of tropisetron after anaesthesia induction is associated with statistically significant decreased early post-operative pain in patients undergoing gynaecological laparoscopies under sevoflurane based general anaesthesia.
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In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain. ⋯ Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.
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The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile. ⋯ Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon.