IntroductionCeftriaxone (CFX) and clavulanic acid (CA) are 2 β-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects.MethodsThe carrageenan (Carr) test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-α and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay.ResultsBoth CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-α and IL-10 serum concentrations at different times.ConclusionOur results provide evidence that both CFX and CA cause an analgesic effect on a Carr inflammatory pain model and that said analgesic effect differs between each β-lactam molecule. Furthermore, this effect may be related to an anti-inflammatory effect of both molecules and a direct TNF-α and IL-10 serum concentration modulation.

The evidence supporting the use of pharmacological treatments in pediatric chronic pain is limited. Quantitative sensory testing (QST) and conditioned pain modulation evaluation (CPM) provide information on pain phenotype, which may help clinicians to tailor the treatment. This retrospective study aimed to evaluate the association between the use of QST/CPM phenotyping on the selection of the treatment for children with chronic pain conditions. We retrospectively analyzed the medical records of 208 female patients (mean age 15 ± 2 years) enrolled in an outpatient interdisciplinary pediatric complex pain center. Pain phenotype information (QST/CPM) of 106 patients was available to the prescribing physician. The records of 102 age- and sex-matched patients without QST/CPM were used as controls. The primary endpoint was the proportion of medications and interventions prescribed. The secondary endpoint was the duration of treatment. The QST/CPM group received less opioids (7% vs. 28%, respectively, p < 0.001), less anticonvulsants (6% vs. 25%, p < 0.001), and less interventional treatments (29% vs. 44%, p = 0.03) than controls. Patients with an optimal CPM result tended to be prescribed fewer antidepressants (2% vs. 18%, p = 0.01), and patients with signs of allodynia and/or temporal summation tended to be prescribed fewer NSAIDs (57% vs. 78%, p = 0.04). There was no difference in the duration of the treatments between the groups. QST/CPM testing appears to provide more targeted therapeutic options resulting in the overall drop in polypharmacy and reduced use of interventional treatments while remaining at least as effective as the standard of care.

Study Objectives Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause. Methods Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-minute wake periods and nap opportunities for ≥48 hours in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure. Results In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women. Conclusion These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause.