Articles: itch.
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This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.
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GABAA receptors in the central nucleus of amygdala are involved in pain- and itch-related responses.
Itch and pain are unpleasant sensations that distress many patients with disease. However, most studies have focused on the neural mechanisms of pain, and much less effort has been devoted to itch. It has been reported that itch and pain might share a common pathway, and γ-aminobutyric acid type A (GABA(A)) receptors in the central nucleus of the amygdala (CeA) are involved in pain modulation. However, the contribution of GABAA receptors in the CeA to the modulation of itch remains poorly understood. Herein, we report that bilateral intra-CeA microinjection of a selective GABAA receptor agonist muscimol hydrochloride (Mus; 50 ng per side), but not a selective GABAA receptor antagonist bicuculline (Bic; 20 ng per side) or vehicle, showed significant analgesic effects, reflected by an increase in tail-flick latency and a decrease in allyl isothiocyanate (mustard oil)-evoked ipsilateral forelimb wipes. More importantly, rats subjected to intra-CeA infusion of Bic showed a significantly greater number of scratching bouts and time in acute and chronic pruritus animal models than control rats. Conversely, intra-CeA infusion of Mus in animal models dramatically decreased the number of scratching bouts and time compared with control rats. In addition, intra-CeA infusion of Bic or Mus at the current dose had no obvious effects on other behaviors including locomotor activity and spontaneous facial grooming in rats subjected to cheek microinjection of 5-hydroxytryptamine. Taken together, these results indicate that the GABA(A) receptor-mediated inhibitory system in the CeA is involved in itch modulation as well as is known in pain control. ⋯ Itch, especially chronic itch, remains a challenge in clinic. Results of this study showed that the GABAA receptors in the CeA play an important role in itch modulation, which might help us to better understand the mechanisms of itch and subsequently develop novel mechanisms-based strategies to treat chronic itch in clinic.
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Notalgia paresthetica (NP) is a focal neuropathic itch condition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging. In this case-series three female NP patients were treated with 8% capsaicin patches following a spatial quantification of their alloknetic area with a von Frey filament. ⋯ Although 8% topical capsaicin relieved itch in all three patients, the duration of the effectiveness varied greatly from only 3 days to >2 months. The treatment was well tolerated in the patients and there appear to be no significant hindrances to applying this treatment with NP as an indication, although it may only exhibit satisfactory effectiveness in certain patients. Placebo-controlled double-blinded trials are needed to confirm the effectiveness of the treatment and assess predictive parameters of the treatment outcome.
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There are substantial disagreements about the expression of gastrin-releasing peptide (GRP) in sensory neurons and whether GRP antibody cross-reacts with substance P (SP). These concerns necessitate a critical revaluation of GRP expression using additional approaches. Here, we show that a widely used GRP antibody specifically recognizes GRP but not SP. ⋯ Our comprehensive study demonstrates that a majority of GRPergic fibers are of primary afferent origin. A number of factors such as low copy number ofGrptranscripts, small percentage of cells expressingGrp, and the use of an eGFP GENSAT transgenic as a surrogate for GRP protein have contributed to the controversy. Optimization of experimental procedures facilitates the specific detection of GRP expression in dorsal root ganglia neurons.
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Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. ⋯ Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway.