Pain
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Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel that functions as an integrator of multiple pain stimuli including heat, acid, capsaicin and a variety of putative endogenous lipid ligands. TRPV1 antagonists have been shown to decrease inflammatory pain in animal models and to produce limited hyperthermia at analgesic doses. Here, we report that ABT-102, which is a potent and selective TRPV1 antagonist, is effective in blocking nociception in rodent models of inflammatory, post-operative, osteoarthritic, and bone cancer pain. ⋯ Although a single dose of ABT-102 produced a self-limiting increase in core body temperature that remained in the normal range, the hyperthermic effects of ABT-102 effectively tolerated following twice-daily dosing for 2 days. Therefore, the present data demonstrate that, following repeated administration, the analgesic activity of TRPV1 receptor antagonists is enhanced, while the associated hyperthermic effects are attenuated. The analgesic efficacy of ABT-102 supports its advancement into clinical studies.
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Randomized Controlled Trial Clinical Trial
Opposite effects of opioid blockade on the blood pressure-pain relationship in depressed and non-depressed participants.
The effect of the opioid antagonist naltrexone on the relationship between blood pressure and pain was examined in 24 participants with major depressive disorder and 31 non-depressed controls, before and after 25 min of stressful mental arithmetic. Pain was induced by immersing the non-dominant foot in 2 degrees C ice-water for as long as possible or until 4 min had elapsed (the cold pressor test). Blood pressure was measured before each cold pressor test, and at 2-min intervals during mental arithmetic. ⋯ However, naltrexone unmasked an association between blood pressure and pain--those with highest blood pressure reported least cold-induced pain. Thus, endogenous opioids apparently masked an analgesic mechanism linking elevated blood pressure with reduced sensitivity to pain in participants with major depressive disorder. Noradrenergic mechanisms involved in active coping, stress-induced analgesia and baroreflexes might account for these findings.
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The present study investigated the effect of the child's pain catastrophizing and self-reported pain upon the child's facial expression of pain and parental inferences of their child's pain. School children (n=62) experienced pain by taking part in a cold water procedure. Analyses revealed that more intense pain was associated with higher levels of facial pain expression in children who reported a low frequency of catastrophizing. ⋯ A similar pattern was obtained for the pain inferences by the parent: pain intensity as reported by the child was positively related to pain inferences by the parent in children who reported a low frequency of catastrophizing, but such relationship was not significant for children with high catastrophizers. Further analyses revealed that when pain intensity was low, parents of high catastrophizing children judged the pain of their child to be higher than parents of low catastrophizing children. The implications of the findings are discussed in terms of the importance of assessing different dimensions of pain encoded in expression, different types of pain expression, and its differential effects upon others.
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Relatively little is known on pain-induced neurotransmitter release in the human cerebral cortex. We used proton magnetic resonance spectroscopy (1H-MRS) during tonic painful heat stimulation to test the hypothesis of increases in both glutamate and GABA, two neurotransmitters with a key role in pain processing. Using a 3T MR scanner, we acquired spectra from the rostral anterior cingulate cortex (rACC) in 13 healthy right-handed subjects at rest and during painful heat stimulation. ⋯ No changes in glutamate concentrations were detected during noxious stimulation. This study provides the first evidence that GABA is released in the human cerebral cortex during painful stimulation. The results are in line with animal findings on the role of GABA in pain processing and with studies in humans showing analgesic efficacy of GABA-related drugs in clinical pain conditions.