Lesion-induced sprouting promotes neurophysiological integration of septal and entorhinal inputs to granule cells in the dentate gyrus of rats.

Axonal sprouting of dentate gyrus (DG) afferents after entorhinal cortex (EC) lesion is a model preparation to assess lesion-induced functional reorganization in a denervated target structure. Following a unilateral EC lesion, the surviving contralateral entorhinal projection, termed the crossed temporodentate pathway (CTD), and the heterotypic septal input to the DG, the septodentate pathway (SD), undergo extensive axonal sprouting. We explored whether EC lesion alters the capacity of the SD pathway to influence CTD-evoked granule cell excitability in the DG. We recorded extracellular field excitatory postsynaptic potentials (fEPSPs) after CTD stimulation alone and paired SD-CTD stimulation. Male rats were given unilateral EC lesions or sham operations; evoked fEPSPs in the DG were recorded at 4-, 15-, and 90-days post-entorhinal lesion to assess functional reorganization of the CTD and SD pathways. We found significantly increased fEPSP amplitudes in cases with unilateral lesions compared to sham-operates at 15- and 90-days post lesion. Within each time point, paired SD-CTD stimulation resulted in significantly depressed fEPSP amplitudes compared to amplitudes evoked after CTD stimulation alone and this effect was solely seen in cases with EC lesion. In cases where granule cell discharge was observed, SD stimulation increased discharge amplitude elicited by the CTD stimulation at 90-days postlesion. These findings demonstrate that synaptic remodeling following unilateral cortical lesion results in a synergistic interaction between two established hippocampal afferents that is not seen in uninjured brains. This work may be important for models of neurodegenerative disease and neural injury that target these structures and associated hippocampal circuitry.

Chronic low back pain comorbidity count and its impact on exacerbating opioid and non-opioid prescribing behavior.

RESEARCH OBJECTIVES: The objective of the study was to determine the characteristics of chronic low back pain (CLBP) comorbidity and its impact on opioid and non-opioid treatments among Chicagoland patients with CLBP. DESIGN: A retrospective cross-sectional study comparing differences in comorbidity and treatment patterns among Chicagoland patients with CLBP against a matched control arm without chronic low back pain (NCLBP). SETTING: Academic hospital system outpatient services. PARTICIPANTS: Using the International Classification of Diseases, 10th Revision codes (ICD 10) 9589 patients were identified with CLBP with a median age of 57 years old and 62.32% female distribution. The NCLBP group comprised 9589 age-, sex-, race-, and region-matched patients. RESULTS: An increased prevalence across all 17 studied comorbidities was found in CLBP patients as compared to NCLBP patients. CLBP patients carried an average of 3.5 comorbidities compared with 2.4 comorbidities in NCLBP patients. Rheumatoid arthritis (RA), joint arthritis, and obesity had the strongest relationship with CLBP. Additionally, we found that the most prescribed treatment for CLBP were opioids, which ranked above NSAIDs and physical therapy. 56% of CLBP patients were prescribed opioids as compared to 36% of NCLBP patients (Odds Ratio = 2.28, 95% CI: 2.16-2.42). Tramadol was the agent with the strongest relationship to CLBP. CLBP patients were more likely to use two or more opioids concomitantly. The number of total treatments was positively associated with the number of comorbidities in both CLBP and NCLBP patients (Cochran-Armitage trend test p < 0.0001). CONCLUSIONS: Chronic low back pain patients showed a higher number of comorbidities than their NCLBP counterparts. Comorbidity count trended positively with higher treatment burden with opioids being the most prescribed treatment, often with poly-opioid use, over conservative modalities such as NSAIDs and physical therapy.