The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain.

The complement cascade is a key component of the innate immune system that is rapidly recruited through a cascade of enzymatic reactions to enable the recognition and clearance of pathogens and promote tissue repair. Despite its well-understood role in immunology, recent studies have highlighted new and unexpected roles of the complement cascade in neuroimmune interaction and in the regulation of neuronal processes during development, aging, and in disease states. Complement signaling is particularly important in directing neuronal responses to tissue injury, neurotrauma, and nerve lesions. Under physiological conditions, complement-dependent changes in neuronal excitability, synaptic strength, and neurite remodeling promote nerve regeneration, tissue repair, and healing. However, in a variety of pathologies, dysregulation of the complement cascade leads to chronic inflammation, persistent pain, and neural dysfunction. This review describes recent advances in our understanding of the multifaceted cross-communication that takes place between the complement system and neurons. In particular, we focus on the molecular and cellular mechanisms through which complement signaling regulates neuronal excitability and synaptic plasticity in the nociceptive pathways involved in pain processing in both health and disease. Finally, we discuss the future of this rapidly growing field and what we believe to be the significant knowledge gaps that need to be addressed.

Work and social adjustment in patients with anorexia nervosa.

OBJECTIVE AND METHODS: The Work and Social Adjustment Scale (WSAS) assesses patients' perceptions of impairment in everyday functioning and has been reported as a simple and reliable self-report measure in different psychiatric disorders. This study compared WSAS data from an anorexia nervosa (AN) patient group with that from healthy controls (HCs) and published data from other patient groups. A total of 160 female participants (AN, 77; HC, 83) completed the WSAS as well as measures of eating disorder symptom severity and brief assessments of anxiety and depression. RESULTS: Work and Social Adjustment Scale scores for the AN group were found to be in the severely impaired range, whereas the scores for those within the HC group indicated very little, or no impairment. Total WSAS scores in the AN group were significantly correlated with severity of clinical symptoms, and eating disorder-specific symptoms were the best predictor of social and occupational functional impairment. The greatest impairment in the AN group was reported in the realm of social leisure. CONCLUSIONS: Consistent with reports in other clinical populations, it is suggested that the WSAS could be an extremely useful and meaningful measure to assess social and occupational functioning in people with eating disorders, in addition to eating disorder-specific assessments.

Stay or go? Neuronal activity in medial frontal cortex during a voluntary tactile preference task in head-fixed mice.

The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant sensation in the cortex involves multiple brain regions, although the specific role of the brain areas involved in voluntary, rather than reflexive movement away from unpleasant stimuli is not well understood. Here, we focused on the medial subdivision of secondary motor cortex, which is proposed to link sensory and contextual cues to motor action, and tested its role in controlling voluntary movement in the context of an aversive tactile cue. We designed a novel, 3D-printed tactile platform consisting of innocuous (grid) and mildly noxious (spiked) surfaces (50:50 % of total area), which enabled monitoring neuronal activity in the medial frontal cortex by two-photon imaging during a sensory preference task in head-fixed mice. We found that freely moving mice spent significantly less time on a spiked-surface, and that this preference was eliminated by administration of a local anesthetic. At the neuronal level, individual neurons were differentially modulated specific to the tactile surface encountered. At the population level, the neuronal activity was analyzed in relation to the events where mice chose to "stop-on" or "go-from" a specific tactile surface and when they "switched" surfaces without stopping. Notably, each of these three scenarios showed population activity that differed significantly between the grid and spiked tactile surfaces. Collectively, these data provide evidence that tactile quality is encoded within medial frontal cortex. The task pioneered in this study provides a valuable tool to better evaluate mouse models of nociception and pain, using a voluntary task that allows simultaneous recording of preference and choice.