RESUMO
Introduction: Dysmenorrhea is associated with increased risk of chronic pain and hyperalgesia. Menstruating individuals with dysmenorrhea are more likely to have elevated pain reactivity when experiencing experimental pain, than those without. However, no study has examined intragroup differences in reactions to experimentally induced pain for individuals with dysmenorrhea. The main aim of this study was to examine the relative roles of dysmenorrhea severity and interference in the experience of experimentally-induced pain. Methods: Participants were 120 menstruating individuals involved in a larger research study examining the influence of expectations on experimentally-induced pain. As part of the study, participants completed an online questionnaire regarding demographic and menstrual information and participated in a cold pressor task. Participants were randomized into four groups based on the manipulation of two independent variables: (1) high vs. low expectations about pain severity (pain-expectations); (2) and high vs. low expectations about one's pain tolerance (self-expectations). Participants verbally rated their pain severity throughout the cold pressor task using a 0-10 scale. Regression analyses were conducted examining the relationships between dysmenorrhea experience (i.e., average severity and interference) and cold pressor data [pain severity ratings and pain tolerance (i.e., total time in the cold pressor)], controlling for the manipulated expectations and age. Then, moderation analyses were conducted examining expectation group differences. Results: When controlling for manipulated expectations and age, dysmenorrhea severity significantly predicted initial pain severity rating (p = 0.022) but did not predict final pain severity rating (p = 0.263) or pain tolerance (p = 0.120). Dysmenorrhea interference did not predict initial pain severity rating (p = 0.106), final pain severity rating (p = 0.134), or pain tolerance (p = 0.360). A moderation analysis indicated that the relationship between dysmenorrhea severity and initial pain severity rating was not moderated by pain-expectations, χ 2(1) = 0.412, p = 0.521. Discussion: During an experimentally-induced pain task, dysmenorrhea severity but not interference predicted initial pain severity rating, such that higher levels of dysmenorrhea severity predicted greater initial pain severity rating. This suggests individuals with more severe dysmenorrhea pain may experience greater initial sensitivity to pain and be at risk for increased sensitivity to acute pain and potentially the development of chronic pain.
RESUMO
Dendritic cells (DC) can be divided into three subsets, Langerhans cells, myeloid DC (MDC), and lymphoid DC (LDC), based upon phenotypic and functional differences. We hypothesized that different DC subsets are associated with the development of protective vs nonprotective cell-mediated immune (CMI) responses against the fungal pathogen, Cryptococcus neoformans. To test this, mice were immunized with protective and/or nonprotective immunogens, and DC subsets in draining lymph nodes were assessed by flow cytometry. The protective immunogen (cryptococcal culture filtrate Ag-CFA), in contrast to the nonprotective immunogen (heat-killed cryptococci-CFA), the nonprotective immunogen mixed with the protective immunogen (cryptococcal culture filtrate Ag + heat-killed cryptococci-CFA), or controls, stimulated significant increases in total leukocytes, Langerhans cells, MDC, LDC, and activated CD4+ T cells in draining lymph nodes. The protective immune response resulted in significantly increased levels of anticryptococcal delayed-type hypersensitivity reactivity and activated CD4+ T cells at the delayed-type hypersensitivity reaction site. Draining lymph node LDC:MDC ratios induced by the protective immunogen were significantly lower than the ratios induced by either immunization in which the nonprotective immunogen was present. In contrast, mice given the nonprotective immunogen had LDC:MDC ratios similar to those of naive mice. Our data indicate that lymph node Langerhans cells and MDC are APC needed for induction of the protective response. The predominance of LDC in mice undergoing nonprotective responses suggests that lymph node LDC, like splenic LDC, are negative regulators of CMI responses. In addition to showing DC subsets associated with functional differences, our data suggest that the LDC:MDC balance, which can be modulated by the Ag, determines whether protective or nonprotective anticryptococcal CMI responses develop.