Pain
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Human unmyelinated (C) tactile afferents signal the pleasantness of gentle skin stroking on hairy (nonglabrous) skin. After neuronal injury, that same type of touch can elicit unpleasant sensations: tactile allodynia. The prevailing pathophysiological explanation is a spinal cord sensitization, triggered by nerve injury, which enables Aβ afferents to access pain pathways. ⋯ In addition, reduced activation in the medial prefrontal cortices, key areas for C-tactile hedonic processing, was identified. These findings suggest that dynamic tactile allodynia is associated with reduced C-tactile mediated hedonic touch processing. Nevertheless, because the patients did not develop allodynic pain, this seems dependent on Aβ signaling, at least under these experimental conditions.
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We studied the number of musculoskeletal pain sites as a predictor of sickness absence during a 7-year follow-up among a nationally representative sample (the Health 2000 survey) of occupationally active Finns 30 to 55years of age (3420 subjects who did not retire or die during the follow-up). Baseline data (questionnaire, interview, clinical examination by a physician) were gathered in 2000 to 2001 and linked with information from national registers on annual compensated sickness absence periods (⩾10workdays) covering the years 2002 to 2008. Pain during the preceding month in 18 body locations was inquired and combined into 4 sites (neck, upper limbs, low back, lower limbs). ⋯ The confidence intervals of the ORs did not include unity. The adjusted ORs for belonging to the Ascending trajectory were 1.1, 1.3, 1.7, and 1.7, respectively. As the number of pain sites was a strong independent predictor of work absenteeism, early screening of workers with multisite pain and interventions to support work ability seem warranted.
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Recent evidence indicates that pain-related fear can be acquired through associative learning. In the clinic, however, spreading of fear and avoidance is observed beyond movements/activities that were associated with pain during the original pain episode. One mechanism accounting for this spreading of fear is stimulus generalization. ⋯ These data illustrate that spreading of pain-related fear is fostered by previously acquired movement-pain contingencies. Based on recent advances in anxiety research, we proposed an innovative approach conceptualizing predictable pain as a laboratory model for fear of movement in regional musculoskeletal pain, and unpredictable pain generating contextual pain-related fear as a prototype of widespread musculoskeletal pain. Consequently, fear generalization might play an important role in spreading of pain-related fear and avoidance behavior in regional and widespread musculoskeletal pain.
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T-type calcium channels encoded by the Ca(V)3.2 isoform are expressed in nociceptive primary afferent neurons where they contribute to hyperalgesia and thus are considered as a potential therapeutic target to treat pathological pain. Here we report that the small organic state-dependent T-type channel antagonist TTA-A2 efficiently inhibits recombinant and native Ca(V)3.2 currents. Although TTA-A2 is a pan Ca(V)3 blocker, it demonstrates a higher potency for Ca(V)3.2 compared to Ca(V)3.1. ⋯ Oral administration of TTA-A2 produced a dose-dependent reduction of hypersensitivity in an IBS model, demonstrating its therapeutic potential for the treatment of pathological pain. Overall, our results suggest that the high potency of TTA-A2 in the depolarized state strengthen its analgesic efficacy and selectivity toward pathological pain syndromes. This characteristic would be beneficial for the development of analgesics targeting T-type channels, in particular for the treatment of pain associated with IBS.
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Hemiplegic shoulder pain (HSP) is common after stroke. Whereas most studies have concentrated on the possible musculoskeletal factors underlying HSP, neuropathic aspects have hardly been studied. Our aim was to explore the possible neuropathic components in HSP, and if identified, whether they are specific to the shoulder or characteristic of the entire affected side. ⋯ Those with HSP had higher heat-pain thresholds in both the affected shoulder (P<0.001) and leg (P<0.01), exhibited higher rates of hyperpathia in both these regions (each P<0.001), and more often reported chronic pain throughout the affected side (P<0.001) than those without HSP. The more prominent sensory alterations in the shoulder region suggest that neuropathic factors play a role in HSP. The clinical evidence of damage to the spinothalamic-thalamocortical system in the affected shoulder and leg, the presence of chronic pain throughout the affected side, and the more frequent involvement of the parietal cortex all suggest that the neuropathic component is of central origin.