Pain
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Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. ⋯ Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.
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Repetitive transcranial magnetic stimulation (rTMS) has had partly incongruous effects on cutaneous sensibility, and there are no systematic studies on the effects of rTMS on facial sensory function. We assessed modulation of thermal sensitivity of facial skin in healthy subjects by navigated rTMS (10 Hz), enabling accurate localization of predefined cortical targets: right primary motor cortex (M1) of facial muscles, primary somatosensory cortex (S1) representing the cheek, dorsolateral prefrontal cortex (DLPFC), and secondary somatosensory cortex (S2); the control site was occipital cortex (OCC). Applying signal detection theory, we investigated whether the rTMS-induced changes in heat-pain threshold (HPT) relate to an alteration in the subject's discriminative capacity (sensory factor) or response criterion (non-sensory factor). ⋯ Stimulation of M1 decreased capacity to discriminate painful heat without influencing HPT; there was large interindividual variation in rTMS effects in the M1/S1 areas. Detection threshold for innocuous warming rose similarly after rTMS of M1, S1, DLPFC, S2 and OCC, whereas sensibility to innocuous cooling transiently improved after rTMS of S1. The results indicate that rTMS applied anatomically accurately to S2 may produce analgesia in the face via multiple mechanisms, partly depending on gender, and involving decreased discriminative capacity and increased response criterion.
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The present study was carried out to examine global gene expression in the brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice that received facial carrageenan injection showed increased mechanical allodynia, demonstrated by increased responses to von Frey hair stimulation of the face. The brainstem was harvested at 3 days post-injection, corresponding to the time of peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. ⋯ Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin mediates the capturing of leukocytes from the bloodstream and rolling of leukocytes along the endothelial surface. We hypothesize that increased nociceptive input to the brainstem could attract circulating macrophages into the brain, resulting in neuroinflammation and pain.
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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.