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Regulation of mechanical hypersensitivity in a model of neuropathic pain by endogenous and exogenous amyloid-beta in the spinal dorsal horn.
We hypothesize that Ab contributes to synaptic plasticity and sensory processing in the spinal dorsal horn. Our overall aim is to modulate Ab in the spinal dorsal horn to improve hypersensitivity in pain models. Sensory sensitivity was tested using Von Frey and Hargreaves. These technologies promise to reveal new molecular pathways and thereby provide the basis for novel treatments for disease. However, the majority of omics studies focus on describing a phenomenon or providing an atlas rather than finding a treatment.
Methods : Here, intending to close the knowledge gap, we designed a MedSeek, multi-targeting design R package that predicts potential treatments from already approved drugs by starting with data on of differentially expressed genes DEGs. MedSeek then interrogates the drug-gene interaction database DGIb for approved therapies and calculates the drug impact score based on the integrated value of influence IVI for each node.
Results : We tested this approach by inputting genes found to be differentially expressed in the spinal dorsal horn after peripheral nerve injury, a model of neuropathic pain, in two rodent species in both males and females. We found that administering R, the active metabolite of fostamatinib, significantly reversed pain hypersensitivity in both sexes. Thus, we believe this approach can be useful for finding new indications for existing drugs.
