Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain

Hydration in sport and exercise

Hypohydration, defined as a deficit in total body water that exceeds normal daily fluid fluctuations, is typically set as a fluid loss equivalent to >2% of body mass. The evaporation of sweat provides the principle means of heat dissipation during exercise in the heat; typical sweat rates of 300–2000 mL/h during sporting activities are generally not matched by fluid intake, leading to hypohydration. Although there are shortcomings in the literature related to hypohydration and sports performance, it is likely that some scenarios (hot conditions, larger fluid losses and prolonged aerobic exercise) are more at risk of incurring impaired performance. Guidelines for fluid intake during exercise and sporting activity are contentious since they need to span situations in which it is easy to overdrink compared with sweat losses and others in which significant levels of hypohydration occur. Nevertheless, athletes can be guided to develop fluid intake plans that are suited to their specific needs