Articles: hyperalgesia.
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The aim of this study was to investigate whether the injection of nerve growth factor induces spontaneous nociceptive behavior in the intact or sensitized temporomandibular joint (TMJ) of rats. ⋯ Taken together, these results indicate that NGF can induce TMJ nociception during TMJ inflammation. Moreover, the expression of this nociceptive response seems to depend on the synergic activity of NGF and sympathetic amines released during TMJ inflammation acting on beta2-adrenergic receptors.
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Previous studies suggest that nocebo effects, sometimes termed "negative placebo effects," can contribute appreciably to a variety of medical symptoms and adverse events in clinical trials and medical care. In this study, using a within-subject design, we combined functional magnetic resonance imaging (fMRI) and an expectation/conditioning manipulation model to investigate the neural substrates of nocebo hyperalgesia using heat pain on the right forearm. ⋯ Functional connectivity analysis of spontaneous resting-state fMRI data from the same cohort of subjects showed a correlation between two seed regions (left frontal operculum and hippocampus) and pain network including bilateral insula, operculum, ACC, and left S1/M1. In conclusion, we found evidence that nocebo hyperalgesia may be predominantly produced through an affective-cognitive pain pathway (medial pain system), and the left hippocampus may play an important role in this process.
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Randomized Controlled Trial Comparative Study
Effect of morphine and pregabalin compared with diphenhydramine hydrochloride and placebo on hyperalgesia and allodynia induced by intradermal capsaicin in healthy male subjects.
Intradermal (ID) capsaicin injection in humans induces spontaneous pain, flare, primary hyperalgesia, secondary hyperalgesia, and allodynia. Secondary hyperalgesia and allodynia are a reflection of central sensitization. The effect of treatment of single doses of (1) pregabalin, 300 mg single oral dose, and (2) morphine, 10 mg IV, on the area of secondary hyperalgesia induced by ID capsaicin injection was studied by using a randomized, double-blinded, placebo-controlled, 4-period, cross-over design in 20 healthy men. Compared with active placebo diphenhydramine (50 mg oral dose), pregabalin and morphine significantly reduced the area of secondary hyperalgesia over 15 to 240 minutes after capsaicin injection (approximately 25%, P = .002 and approximately 33%, P < .001, respectively). A smaller reduction was observed when pregabalin and morphine were compared with true placebo (approximately 13%, P = .081 and approximately 24%, P = .009, respectively). Diphenhydramine, on the other hand, increased the area of secondary hyperalgesia in comparison with true placebo (approximately 16%, P = .061). The relationship between the baseline area of hyperalgesia and assay sensitivity suggests that establishing minimum entry criteria for the baseline area of hyperalgesia requirement increases the sensitivity of the assay. ⋯ These results suggest that the minimally invasive intradermal capsaicin model, when it is compared with true placebo, can potentially be used for an early assessment of relevant pharmacology of novel analgesic compounds in healthy subjects. This platform may provide a means to rapidly assess new analgesics and enhance dose selection and decision-making during clinical development.
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Prostaglandins Leukot. Essent. Fatty Acids · Dec 2008
COX-2 expression and function in the hyperalgesic response to paw inflammation in mice.
Peripheral inflammation and edema are often accompanied by primary and secondary hyperalgesia which are mediated by both peripheral and central mechanisms. The role of cyclooxygenase-2 (COX-2)-mediated prostanoid production in hyperalgesia is a topic of substantial current interest. We have established a murine foot-pad inflammation model in which both pharmacologic and genetic tools can be used to characterize the role of COX-2 in hyperalgesia. ⋯ Zymosan-induced primary hyperalgesia in Cox-2-/- mice is similar to that of their Cox-2+/+ littermate controls. However, the central component of hyperalgesia is substantially reduced in Cox-2-/- versus Cox-2+/+ mice, and returns to baseline values much more rapidly. Thus pharmacological data suggest, and genetic experiments confirm, (i) that primary hyperalgesia in response to zymosan inflammation in the mouse paw is not mediated by COX-2 function and (ii) that COX-2 function plays a major role in the central component of hyperalgesia in this model of inflammation.
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Human brain mapping · Dec 2008
Representation of UV-B-induced thermal and mechanical hyperalgesia in the human brain: a functional MRI study.
Surrogate models of pain and hyperalgesia allow the investigation of underlying mechanisms in healthy volunteers. Here, we investigated brain activation patterns during mechanical and heat hyperalgesia in an inflammatory human pain model using functional magnetic resonance imaging. Heat and mechanical hyperalgesia were induced on the right forearm by UV-B application in 14 healthy subjects. ⋯ We conclude that different types of hyperalgesia in a human surrogate model of inflammatory pain produce different brain activation patterns. This is partly due to a differential processing of thermal and mechanical pain and an interaction of sensitization and modality in the caudal portion of the IFC. Finally, the data provide evidence for the existence of a common "sensitization network" consisting of ACC, bilateral anterior insula, and parts of the IFC.