Pain
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This systematic investigation of the neurocognitive correlates of complex regional pain syndrome (CRPS) in a single case also reports agnosia for object orientation in the context of persistent CRPS. We report a patient (JW) with severe long-standing CRPS who had no difficulty identifying and naming line drawings of objects presented in 1 of 4 cardinal orientations. In contrast, he was extremely poor at reorienting these objects into the correct upright orientation and in judging whether an object was upright or not. ⋯ The neuroanatomical correlates are discussed. The patient had no structural brain lesion, raising the possibility that nonstructural reorganisation of cortical networks may be responsible for his deficits. Other patients with CRPS may have related neurocognitive defects.
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The neuropeptide bradykinin (BK) sensitizes nociceptor activation following its release in response to inflammatory injury. Thereafter, the bioactivity of bradykinin is controlled by the enzymatic activities of circulating peptidases. One such enzyme, the metalloendopeptidase EC3.4.24.15 (EP24.15), is co-expressed with bradykinin receptors in primary afferent neurons. ⋯ In addition, bradykinin-induced sensitization of TRPV1 activation was increased in the presence of the EP24.15/16 inhibitor JA-2. Furthermore, behavioral analyses illustrated a significant dose-response relationship between JA-2 and bradykinin-mediated thermal hyperalgesia. These results indicate an important physiological role for the metallopeptidases EP24.15 and EP24.16 in regulating bradykinin-mediated sensitization of primary afferent nociceptors.
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Multicenter Study
Elevated levels of gonadotrophins but not sex steroids are associated with musculoskeletal pain in middle-aged and older European men.
The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79 years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. ⋯ Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR=1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR=1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men.
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Electrical high-frequency stimulation (HFS) of skin afferents elicits long-term potentiation (LTP)-like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP-like pain plasticity. HFS in healthy subjects (n=55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). ⋯ Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer-lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders.