Neuroscience
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The basolateral amygdala (BL) is a putative site for regulating anxiety, where inhibition and excitation respectively lead to decreases and increases in anxiety-like behaviors. The BL contains local networks of GABAergic interneurons that are subdivided into classes based on neurochemical content, and are hypothesized to regulate unique functional responses of local glutamatergic projection neurons. Recently it was demonstrated that lesioning a portion of the BL interneuronal population, those interneurons that express neurokinin1 receptors (NK(1r)), resulted in anxiety-like behavior. ⋯ In addition to enhancing the phenotypic characterization, the extent to which the NK(1r) cells of amygdala nuclei contribute to anxiety-like responses was also investigated. Lesioning the NK(1r) expressing interneurons, with a stable form of substance P (SSP; the natural ligand for NK(1r)) coupled to the targeted toxin saporin (SAP), in the anterior and posterior divisions of the BL was correlated to increased anxiety-like behaviors compared to baseline and control treated rats. Furthermore the phenotypic and regional selectivity of the lesions was also confirmed.
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Tumor necrosis factor-alpha (TNF) is a pro-inflammatory cytokine that is implicated in the initiation of neuropathic pain. Locally administered TNF antagonist etanercept offers a promising new treatment approach to target neuropathic pain. Here we evaluate the distribution and binding specificity for TNF isoforms of locally administered etanercept into injured and uninjured rat sciatic nerve. ⋯ Finally, locally administered etanercept inhibited pain-related behaviors in a rat sciatic nerve crush model. We conclude that locally administered etanercept reaches the endoneurial space in the injured nerve and preferentially binds to transmembrane and bioactive trimer TNF isoforms to modulate neuropathic pain. Locally administered etanercept has potential as a targeted immunomodulating agent to treat local pathogenesis in neuropathic pain after peripheral nerve injury.