Efficacy of mecobalamin (vitamin B12) in the treatment of long-term pain in women diagnosed with fibromyalgia: protocol for a randomised, placebo-controlled trial.

INTRODUCTION: Fibromyalgia causes long-term pain. It affects at least 2% of the population, the majority being women. In addition, extended symptoms corresponding to vitamin B12 deficiency occur. Findings from several studies have indicated that vitamin B12 may be a possible treatment for pain in fibromyalgia. The aim of the proposed study is to evaluate whether vitamin B12 decreases pain sensitivity and the experience of pain (ie, hyperalgesia and allodynia) in women with fibromyalgia. METHODS AND ANALYSIS: The study is a randomised, placebo-controlled, single-blind, clinical trial with two parallel groups which are administered mecobalamin (vitamin B12) or placebo over 12 weeks. 40 Swedish women aged 20-70 years with an earlier recorded diagnosis of fibromyalgia are randomised into the placebo group or the treatment group, each consisting of 20 participants. Outcomes consist of questionnaires measured at baseline and after 12 weeks of treatment. A final re-evaluation will then follow 12 weeks after treatment ends. The primary outcome is tolerance time, maximised to 3 min, which is assessed using the cold pressor test. In order to broaden the understanding of the lived experience of participants, qualitative interviews will be conducted using a phenomenological approach on a lifeworld theoretical basis (reflective lifeworld research approach). ETHICS AND DISSEMINATION: The protocol for the study is approved by the local ethical committee at Linkoping (EPM; 2018/294-31, appendices 2019-00347 and 2020-04482). The principles of the Helsinki Declaration are followed regarding oral and written consent to participate, confidentiality and the possibility to withdraw participation from the study at any time. The results will primarily be communicated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05008042.

Using firefighters as medical first responders to shorten response time in rural areas in Sweden.

OBJECTIVE: To map out and describe an earlier response by using firefighters as medical first responders on while waiting for the ambulance and first incident person assignments focusing on frequency, event time and survival >30 days after performed cardiopulmonary resuscitation. DESIGN: Retrospective descriptive design. SETTING: Ambulance service in a county of southern Sweden with a population of 200 000 inhabitants (23/km2 ). PARTICIPANTS: Data were collected from four data systems within different organizations; emergency medical communication centre, fire deparment, ambulance services and conty hospital analysis unit. MAIN OUTCOME MEASURE(S): Data from 600 while waiting for the ambulance assignments, whereof 120 with first incident person present, collected between 1 January 2012 and 31 December 2016. Between 1 June 2014 and 1 October 2015, the two fire departments were dually dispatched on out-of-hospital cardiac arrests. RESULTS: Three main findings were made: there was a prolonged process time for dispatching fire fighters on while waiting for the ambulance assignments. Dual dispatches did not shorten the process time for dispatching full-time firefighters, and, in a majority of while waiting for the ambulance assignments where cardiopulmonary resuscitation was performed, firefighters or first incident persons arrived first on the scene. CONCLUSION: Minimising every minute that delays the performance of life-saving actions is crucial. By dispatching firefighters on while waiting for the ambulance assignments in rural areas, the response time in a majority of assignments was shortened. However, there was substantial delay in dispatching firefighters due to prolonged process time at the emergency medical communication centre. The emergency medical communication centre operator's ability to quickly assess the need for while waiting for the ambulance assignments plays a crucial role in the chain of survival.

Pain here and now: physical pain impairs transcendence of psychological distance.

BACKGROUND: The ability to traverse psychological distance by going beyond the experienced reality of the self, here and now, is fundamental for effective human functioning. Yet, little is known about how physical pain affects transcendence of psychological distance. Using a construal level theory framework of psychological distance, the current research examines the hypothesis that pain impairs people's ability to traverse any kind of psychological distance whether it be temporal, social, and spatial distance, or the hypothetical. METHODS: Using the cold pressor test, 151 participants participated in an experiment where they were either induced with acute pain (treatment group) or no pain (control group) while completing a battery of questions measuring to what extent their current thoughts were transcending psychological distance. RESULTS: The results were largely consistent with the hypothesis. Relative to the control group, pain induced participants showed significantly less transcendence of past temporal distance, social distance, spatial distance, and the hypothetical. Furthermore, greater self-reported pain intensity was significantly associated with less transcendence of temporal (past and future), social, and spatial distance. CONCLUSION: Physical pain impairs the ability to traverse psychological distance. The research has practical implications for the pain clinic and for pain-afflicted individuals in everyday life.

Influence of estrogen levels on thermal perception, pain thresholds, and pain tolerance: studies on women undergoing in vitro fertilization.

UNLABELLED: We examined the relationship between estrogen and pain in women undergoing in vitro fertilization (IVF). Quantitative sensory tests (QST) were performed twice during the IVF-regimen: once during hormonal down-regulation and once during hormonal up-regulation. A group of healthy men and a group of women using monophasic contraceptives were also examined, to control for session-to-session effects. Among the women undergoing IVF, serum 17ß-estradiol levels differed strongly between treatments as expected, and increased from 65.7 (SD = 26) pmol/L during the down-regulation phase, to 5,188 (SD = 2,524) pmol/L during the up-regulation phase. Significant outcomes in the QST were only seen for temperature perception thresholds (1.7 °C versus 2.2 °C; P = .003) and cold pain threshold (11.5 °C versus 14.5 °C; P = .04). A similar change in cold pain threshold was also seen in the 2 control groups, however, and statistical analysis suggested that this change was due to a session-to-session effect rather than being the result of hormonal modulation. Heat pain thresholds, heat tolerance, pressure pain thresholds, and the cold pressor test showed no significant differences between sessions. These data demonstrate that pain perception and pain thresholds in healthy women show little, if any, changes even with major variations in serum estradiol levels. PERSPECTIVE: This study shows that pain perception and tolerance in women undergoing in vitro fertilization do not vary, despite the dramatic changes in 17ß-estradiol levels induced by the treatment regimen. The result thus suggests that in humans, contrary to experimental animals, changes in estrogen levels have little influence on pain sensitivity.

Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized, placebo-controlled trial.

OBJECTIVES: FM is a condition that preferentially affects women. Sex hormones, and in particular oestrogens, have been shown to affect pain processing and pain sensitivity, and oestrogen deficit has been considered a potentially promoting factor for FM. However, the effects of oestrogen treatment in patients suffering from FM have not been studied. Here, we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM. METHODS: Twenty-nine post-menopausal women were randomized to either 8 weeks of treatment with transdermal 17ß-oestradiol (50 µg/day) or placebo according to a double-blind protocol. A self-estimation of pain, a set of quantitative sensory tests measuring thresholds to temperature, thermal pain, cold pain and pressure pain, and a cold pressor test were performed on three occasions: before treatment, after 8 weeks of treatment and 20 weeks after cessation of treatment. RESULTS: Hormonal replacement treatment significantly increased serum oestradiol levels as expected (P < 0.01). However, no differences in self-estimated pain were seen between treatment and placebo groups, nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points. CONCLUSION: Eight weeks of transdermal oestradiol treatment does not influence perceived pain, pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM. TRIAL REGISTRATION: ClinicalTrials.gov Registration; http://www.clinicaltrials.gov; NCT01087593.

Pain sensations to the cold pressor test in normally menstruating women: comparison with men and relation to menstrual phase and serum sex steroid levels.

The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17beta-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. Hence, these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent.