Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

Randomized, double blind trial of zolpidem 10 mg versus triazolam 0.25 mg for treatment of insomnia in general practice.

OBJECTIVE: To compare the efficacy of two short acting hypnotics, the benzodiazepine triazolam and the imidazopyridine zolpidem, for treatment of insomnia in general practice. DESIGN: Randomized double-blind study. Patients were given triazolam 0.25 mg or zolpidem 10 mg for 14 days. SETTING: Multi-practice comprising 40 general practitioners. SUBJECTS: 178 patients suffering from insomnia were included in the study, data from 139 patients were used in the analyses. MAIN OUTCOME MEASURES: Sleep quality was recorded in the morning (duration of sleep in hours, number of awakenings, and sleep quality on a visual analogue scale (VAS)), and day quality was recorded in the evening (tired/rested, unalert/alert, tired/fresh, all on VAS-scales) during the 14 days' treatment period. RESULTS: We found no statistically significant differences between the two groups regarding sleeping time, number of awakenings, or sleep quality (VAS). Morning feeling (VAS) and day feeling (VAS) were numerically better for zolpidem, although not statistically significant. There was no statistically significant difference in the number of patients experiencing side effects in the two treatment groups. CONCLUSION: On a short-term basis administration of zolpidem (10 mg) appeared as effective and well tolerated as triazolam (0.25 mg)--and thus zolpidem constitutes a suitable alternative for the treatment of insomnia in general practice.

Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice.

In previous separate studies, dexfenfluramine (DF) and ephedrine/caffeine (EC) have been shown to promote weight loss in obese patients as compared with placebo. In order to compare the efficacy and safety of these two anorectic drugs, 103 patients with 20-80% overweight were included in a 15-week double-blind study in general practice. Patients were randomized to either 15 mg DF twice daily (n = 53), or 20 mg/200 mg ephedrine/caffeine three times a day (n = 50), supplementary to a 5 MJ/day diet. Forty-three patients from the DF group and 38 from the EC group completed the study. After 15 weeks of treatment, the DF group (n = 43) had lost 6.9 +/- 4.3 kg and the EC group (n = 38) had lost 8.3 +/- 5.2 kg (mean +/- s.d., P = 0.12). In the subgroup of patients with BMI > or = 30 kg/m2 (n = 59), the mean weight loss was 7.0 +/- 4.2 kg in the DF group (n = 29) and 9.0 +/- 5.3 kg in the EC group (n = 30), P < 0.05. Both systolic and diastolic blood pressures were reduced similarly during both treatments. Twenty-three patients in the DF group (43%) and 27 in the EC group (54%) complained of side-effects. Central nervous system side-effects, especially agitation, were more pronounced in the EC group (P < 0.05), whereas gastro-intestinal symptoms were more frequent in the DF group (P < 0.05). The side-effects declined markedly during the first month of treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)