Articles: hyperalgesia.
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Spinal nociceptive long-term potentiation (LTP) can be induced by high- or low-frequency conditioning electrical stimulation (CES) in rodent preparations in vitro. However, there is still sparse information on the effect of different conditioning frequencies inducing LTP-like pain amplification in humans. In this study, we tested two other paradigms aiming to explore the CES frequency effect inducing pain amplification in healthy humans. ⋯ In the 10 and 200 Hz sessions, the superficial blood flow 10 min after CES was significantly higher than in the control session reaching a plateau after 20 and 10 min, respectively; for the 100 Hz paradigm, a stable level was found without significant differences compared with CES and control sessions. 10 Hz CES caused a lower SF-MPQ score than 100 Hz. High-frequency (200 Hz) and low-frequency (10 Hz) paradigms can induce heterotopic pain amplification similar to the traditional 100 Hz paradigm. The 10 Hz paradigm can be an appealing alternative paradigm in future studies due to its specific association with low-level discharging of C-fibers during inflammation.
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Randomized Controlled Trial
A Randomized, Double-blind, Positive-controlled, 3-way Cross-over Human Experimental Pain Study of a TRPV1 Antagonist (V116517) in Healthy Volunteers and Comparison with Preclinical Profile.
This experimental, translational, experimental pain, single-center, randomized, double-blind, single-dose, 3-treatment, 3-period cross-over proof-of-concept volunteer trial studied the efficacy of a novel TRPV1 antagonist (V116517) on capsaicin- and UV-B-induced hyperalgesia. Heat and pressure pain thresholds, von Frey stimulus-response functions, and neurogenic inflammation were assessed together with safety. Each treatment period was 4 days. ⋯ The TRPV1 antagonists and the COX-2 inhibitor showed different antihyperalgesic profiles indicating different clinical targets. In addition, the preclinical profile of V116517 in rat models of UV-B and capsaicin-induced hypersensitivity was compared with the human experimental data and overall demonstrated an alignment between 2 of the 3 end points tested. The TRPV1 antagonist showed a potent antihyperalgesic action without changing the body temperature but heat analgesia may be a potential safety issue.
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Expert Opin Pharmacother · Sep 2016
Randomized Controlled Trial Comparative StudyEvaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models - the TapCapMentho pilot trial.
Tapentadol is effective in the treatment of neuropathic and nociceptive pain and in acute and chronic pain conditions; two mechanisms combining opioid µ-receptor agonism and noradrenergic reuptake inhibition underlie its analgesic effect. ⋯ The discrepancy between pain models using healthy volunteers and drug trials under real acute and chronic pain conditions in patients as well as methodological aspects may have contributed to this result. The impact of these findings questions the general use of pain models as predictors for early decision making during drug development. The study was registered in ClinicalTrials.gov (NCT01615510).
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This study aimed to compare the reliability and magnitude of conditioned pain modulation (CPM) by applying different test stimuli (TS) and conditioning stimuli (CS). Twenty-six healthy male participants were recruited in the study of two identical sessions. In each session, four TS (electrical, heat, handheld, and cuff pressure algometry) were applied before and during CS (cold pressor test (CPT) or cuff algometry). ⋯ Significant CPM effects were found for all combinations, except the combinations of electrical and heat pain thresholds with cuff CS, which indicates the novel classification of the CPM mechanism. The combinations of handheld pressure and heat pain threshold with CPT would provide the minimum sample size to detect the significant CPM changes in further studies. It is beneficial to provide and compare both ICC and CV to design further clinical trials.
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Anesthesia and analgesia · Sep 2016
PICK1 Regulates the Expression and Trafficking of AMPA Receptors in Remifentanil-Induced Hyperalgesia.
Remifentanil is used widely in clinical anesthesia because it induces more rapid and more common hyperalgesia than other opioid analgesics. Activation of N-methyl-D-aspartate (NMDA) receptors takes a pivotal part in remifentanil-induced hyperalgesia. Like NMDA receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are excitatory ion glutamate receptors in postsynaptic membrane, which are involved in the transmission of both acute and chronic pain. Protein interacting with C kinase 1 (PICK1) plays an important role in NMDA receptor-mediated internalization of glutamate receptor 2 (GluR2)-containing AMPARs and contributes to the induction and maintenance of inflammation-induced pain. This study aimed to test the hypothesis that PICK1 contributes to remifentanil-induced hyperalgesia by regulating AMPAR expression and trafficking in the spinal cord. ⋯ These results indicate that PICK1 deficiency might reverse remifentanil-induced hyperalgesia through regulating GluR2-containing AMPAR expression and trafficking in the spinal cord dorsal horn.