Pain
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The standard rodent model of itch uses scratching with the hind limb as a behavioral response to pruritic stimuli applied to the nape of the neck. The assumption is that scratching is an indicator of the sensation of itch. But because only one type of site-directed behavior is available, one cannot be certain that scratching is not a response to nociceptive or other qualities of sensations in addition to, or instead of, itch. ⋯ In contrast, when the same chemicals were injected into the cheek of the mouse, there were two site-directed behaviors: histamine again elicited scratching with the hind limb, but capsaicin evoked wiping with the forelimb. We conclude that the "cheek model of itch" in the mouse provides a behavioral differentiation of chemicals that elicit predominantly itch in humans from those that evoke nociceptive sensations. That is, the model provides a behavioral differentiation between itch and pain in the mouse.
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The origins of chronic muscle pain development and maintenance are debated regarding the relative contributions of peripheral nociception and central pain processing. Bradykinin (BKN) and kallidin (KAL) have been suggested to be algesic kinins involved in muscle pain. This in vivo study investigates whether there were significant differences in interstitial muscle concentrations of BKN and KAL between chronic work-related trapezius myalgia (TM), chronic whiplash associated disorders (WAD), and healthy controls (CON). ⋯ In chronic pain, positive correlations existed between the two kinins and the difference in pain intensity between recovery and baseline. In this in vivo study of two groups of patients with chronic pain clinically involving the trapezius muscle, we found alterations - most prominent in TM - in the interstitial concentrations of BKN and KAL. The results indicated that the two kinins were involved in aspects of hyperalgesia.
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Accumulating evidence points to significant cognitive disruption in individuals with Fibromyalgia Syndrome (FMS). This study was carried out in order to examine specific cognitive mechanisms involved in this disruption. Standardized experimental paradigms were used to examine attentional function and working memory capacity in 30 women with FMS and 30 matched controls. ⋯ These findings point to disrupted working memory as a specific mechanism that is disrupted in this population. The results of this study suggest that pain in FMS may play an important role in cognitive disruption. It is likely that many factors, including disrupted cognition, play a role in the reduced quality of life reported by individuals with FMS.
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The synaptic vesicle protein synapsin II is specifically expressed in synaptic terminals of primary afferent nociceptive neurons and regulates transmitter release in the spinal cord dorsal horn. Here, we assessed its role in nerve injury-evoked molecular and behavioral adaptations in models of peripheral neuropathic pain using mice genetically lacking synapsin II. Deficiency of synapsin II resulted in reduced mechanical and cold allodynia in two models of peripheral neuropathic pain. ⋯ In addition, the expression of the vesicular glutamate transporters, VGLUT1 and VGLUT2, was strongly reduced in synapsin II knockout mice in the spinal cord. Conversely, synapsin II knockout mice showed a stronger and longer-lasting increase of GABA in lamina II of the dorsal horn after nerve injury than wild type mice. These results suggest that synapsin II is involved in the regulation of glutamate and GABA release in the spinal cord after nerve injury, and that a imbalance between glutamatergic and GABAergic synaptic transmission contributes to the manifestation of neuropathic pain.
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The glial cytokine, interleukin-1beta (IL-1beta), potentiates the excitability of nociceptive trigeminal ganglion (TRG) neurons via membrane depolarization following peripheral inflammation. Perforated patch-clamp technique was used this study to show that the mechanism underlying the excitability of small-diameter TRG neurons following inflammation is due to IL-1beta. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad. ⋯ IL-1beta inhibited I(A) to a significantly greater extent than I(K). These results suggest that the inhibitory effect of I(A) and I(K) currents by IL-1beta in small-diameter TRG neurons potentiates neuronal excitability thereby contributing to trigeminal inflammatory hyperalgesia. These findings provide evidence for the development of voltage-gated K(+) channel openers and IL-1beta antagonists as therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.