Pain
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Patients with temporomandibular disorder (TMD) perform poorly in neuropsychological tests of cognitive function. These deficits might be related to dysfunction in brain networks that support pain and cognition, due to the impact of chronic pain and its related emotional processes on cognitive ability. We therefore tested whether patients with TMD perform poorly in cognitive and emotion tasks and whether they had abnormal task-evoked brain activity. ⋯ These findings suggest that the slow behavioral responses in idiopathic TMD may be due to attenuated, slower, and/or unsynchronized recruitment of attention/cognition processing areas. These abnormalities may be due to the salience of chronic pain, which inherently requires attention. Sluggish performance in cognitive and emotional interference tasks in patients with nontraumatic temporomandibular disorder is associated with pronounced and unsynchronized task-evoked fMRI brain responses.
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Proteinase-activated receptor-4 (PAR(4)) is a G-protein-coupled receptor activated by serine proteinases released during tissue repair and inflammation. We have previously shown that PAR(4) activation sensitises articular primary afferents leading to joint pain. This study examined whether mast cells contribute to this PAR(4)-induced sensitisation and consequent heightened pain behaviour. ⋯ These effects were blocked by pretreatment with cromolyn. These data reveal that PAR(4) is expressed on synovial mast cells and the activation of PAR(4) has a pronociceptive effect that is dependent on mast cell activation. Proteinase-activated receptor-4 is expressed on synovial mast cells, and the activation of Proteinase-activated receptor-4 has a pronociceptive effect that is dependent on mast cell activation.
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It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia. We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. ⋯ Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain.