Pain
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It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund adjuvant (CFA, 0.08mL, 40μg Mycobacterium tuberculosis) into one hind paw of the rat. ⋯ Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for Western blot testing of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time polymerase chain reaction of IL-17RA. The data reveal that IL-17 is up-regulated in activated and nonactivated astrocytes; that IL-17RA is localized in NR1-immunoreactive neurons and up-regulated; and that IL-17 antibody at 2μg/rat significantly increased PWL (P<.05) and decreased p-NR1 and IL-17RA compared to control in CFA- and IL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain.
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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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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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Comparative Study
Variability of "optimal" cut points for mild, moderate, and severe pain: neglected problems when comparing groups.
Defining cut points for mild, moderate, and severe pain intensity on the basis of differences in functional interference has an intuitive appeal. The statistical procedure to derive them proposed in 1995 by Serlin et al. has been widely used. Contrasting cut points between populations have been interpreted as meaningful differences between different chronic pain populations. ⋯ Optimal cut points are strongly influenced by random fluctuations within a sample. Differences in optimal cut points between study groups may be explained by chance variation; no other substantial explanation is required. Future studies that aim to interpret differences between groups need to include measures of variability for optimal cut points.