Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial.

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag®, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly (p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.

The Added Value of Sensitivity to Nonnoxious Stimuli to Predict an Individual's Sensitivity to Pain.

BACKGROUND: Simple tools are needed to predict postoperative pain. Questionnaire-based tools such as the Pain Sensitivity Questionnaire (PSQ) are validated for this purpose, but prediction could be improved by incorporating other parameters. OBJECTIVES: To explore the potency of sensitivity to nonpainful stimuli and biometric data to improve prediction of pain. STUDY DESIGN: Transversal exploratory study. SETTING: Single clinical investigation center. METHODS: Eighty-five healthy volunteers of both genders underwent a multimodal exploration including biometry, questionnaire-based assessment of anxiety, depression, pain catastrophizing, sensitivity to smell, and the PSQ, followed by a psychophysical assessment of unpleasantness thresholds for light and sound, and sensitivity to mechanical, heat, and cold pain. These last 3 parameters were used to calculate a composite pain score. After a multi-step selection, multivariable analyses identified the explanative factors of experimental pain sensitivity, by including biometric, questionnaire-based, and psychophysical nonnociceptive sensitivity parameters, with the aim of having each domain represented. RESULTS: Female gender predicted mechanical pain, a younger age and dark eyes predicted cold pain, and the PSQ predicted heat pain. Sensitivity to unpleasantness of sound predicted mechanical and heat pain, and sensitivity to unpleasantness of light predicted cold pain. Sensitivity to smell was unrelated. The predictors of the composite pain score were the PSQ, the light unpleasantness threshold, and an interaction between gender and eye color, the score being lower in light-eyed men and higher in all women. The final multivariable multi-domain model was more predictive of pain than the PSQ alone (R2 = 0.301 vs 0.122, respectively). LIMITATIONS: Sensitivity to smell was only assessed by a short questionnaire and could lack relevance. Healthy volunteers were unlikely to elicit psychological risk factors such as anxiety, depression, or catastrophizing. These results have not been validated in a clinical setting (e.g., perioperative). CONCLUSION: The predictive potential of the PSQ can be improved by including information about gender, eye color, and light sensitivity. However, there is still a need for a technique suitable for routine clinical use to assess light sensitivity.

Non-specific analgesia during a clinical trial in fibromyalgia.

BACKGROUND: When patients suffering from fibromyalgia undergo a therapeutic trial, a non-negligible part of analgesia is not explained by the drug itself. The mechanisms of this non-specific effect need to be understood. MATERIALS AND METHODS: We undertook secondary analyses of a double-blind randomized trial in fibromyalgia patients in which 100 mg/day milnacipran was not found superior to placebo. Data from 49 patients belonging to both groups were pooled. Both before treatment and one month after treatment, all patients underwent a CaNTAB® neuropsychological test (related to spatial planning, reaction time, decision-making and risk-taking, and ability to name objects), and measurements of sensation and pain thresholds to heat and cold, supraliminal heat pain threshold, punctuate mechanical pain threshold and temporal summation, mechanical allodynia to skin brushing, and response to conditioned pain modulation. We studied the baseline predictors of analgesia and the indicators of change associated to analgesia separately. A stepwise approach was used to select the factors to enter into the final ANCOVAs, in which age, body mass index, treatment group and pain at baseline were covariates. RESULTS: No baseline predictor of non-specific analgesia other than pain at baseline was found to be predictive. Conversely, several neuropsychological (higher performance) or psychophysical (lower sensitivity) changes correlated with analgesia in unadjusted analyses. Multivariable analyses identified increases in warm/heat thermal thresholds and an increased ability to name objects, as factors associated with analgesia. CONCLUSIONS: The changes observed concomitantly to non-specific pain analgesia might be related to mild changes in brain functioning, based on convergent literature data.

Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial.

BACKGROUND: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks. METHODS: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo.The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. RESULTS: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was -0.2 (95% CI [-0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [-0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [-0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event. CONCLUSIONS: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive-emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.

Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study.

INTRODUCTION: Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnacipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if milnacipran could modify the status of conditioned pain modulation (CPM) in patients suffering from fibromyalgia. DESIGN AND SETTING: Randomized, double-blind controlled trial. SUBJECTS AND METHODS: Women with fibromyalgia received milnacipran 100 mg or placebo. The primary end point was the evolution of CPM with treatments after a 30-second painful stimulus. Secondary outcomes included the predictability of milnacipran efficacy from CPM performance, evolution of global pain, mechanical sensitivity, thermal pain threshold, mechanical allodynia, cognitive function, and tolerance. RESULTS: Fifty-four women with fibromyalgia (46.7±10.6 years) were included and randomized, and 24 patients were analyzed in each group. At inclusion, CPM was dysfunctional (CPM30=-0.5±1.9), and global pain was 6.5±1.8. After treatment, there was a nonsignificant CPM difference between milnacipran and placebo (CPM30=-0.46±1.22 vs -0.69±1.43, respectively, p=0.55) and 18.8% vs 6.3% (p=0.085) patients did reactivate CPM after milnacipran vs placebo. Initial CPM was not a predictor of milnacipran efficacy. Global pain, mechanical and thermal thresholds, allodynia, cognition, and tolerance were not significantly different between both groups. CONCLUSION: Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnacipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients.

Intervention Study with Algoplus® : A Pain Behavioral Scale for Older Patients in the Emergency Department.

OBJECTIVES: Evaluation of acute pain is often difficult in older patients admitted to the Emergency Department (ED), and self-evaluation of pain is not always possible. This observational study evaluates how the systematic use of Algoplus® , a validated behavioral scale, could improve pain management of older persons admitted to the ED. METHOD: The intervention study (NCT 02258503) took place in 4 steps in the ED, University Hospital Clermont-Ferrand, France. Pain assessment and analgesics prescription were collected from medical files for 3 months. For 6 months, the whole staff of the ED were trained on pain assessment and to use Algoplus® scale (3-same as step 1). To evaluate the intervention, pain assessment and analgesics prescription were compared before and after implementation by 2-sided tests with a type I error set at α = 0.05. RESULTS: The intervention led to systematic pain evaluation with Algoplus® in 100% of patients (≥ 75 years old, n = 434) and was completed by numeric rating scale (NRS) and other evaluations. Pearson's correlation between NRS ≥ 3 and Algoplus® < 2 was 0.61. Prescription of analgesics (+6%) especially opioids increased nonsignificantly but was similar for all patients whatever the evaluation. CONCLUSIONS: The systematic introduction of Algoplus® scale in the ED allowed a change in practice by improving evaluation and management of pain in patients ≥ 75 years old, especially when difficult to be evaluated. Algoplus® allowed an objective levelling of analgesics prescription in all admitted patients. It also promoted field action to improve pain management in ED.