Peripheral Inflammation Induces C-fos Expression In Hypothalamic Arcuate Nucleus And Its Mechanism

Objective: To study the activation of hypothalamic arcuate nucleus(ARC) neurons during peripheral inflammation in rat, the chemical nature of the activated neurons and the role of NMDA receptor and Src protein tyrosine kinase in this phenomenon.Methods: The peripheral inflammation model was induced by sub-plantar injection of complete Freund’s adjuvant in rats. Pain threshold was measured by radiant heat-withdrawal method. The neuronal activation in ARC was evaluated by c-fos expression. The Fos-immunoreactive positive cells in the whole ARC were counted using unbiased stereological method. The role of NMDA receptor was tested by using its antagonist MK-801, and the role of Src protein tyrosine kinase was tested with its inhibitor PP2. The double immunohistostaining of tyrosine hydroxylase, vesicular glutamate transporter 2 (VGLUT2) orβ-endorphin with Fos expression was used to identify the chemical nature of the activated neurons in ARC.Results: 24 hours after adjuvant injection the pain threshold decreased significantly (P<0.01). During the period of 21 days after adjuvant injection the number of Fos-positive neurons in the whole ARC was up-regulated significantly (P<0.01). Some co-expressions of Fos with tyrosine hydroxylase, VGLUT2 orβ-endorphin were found in ARC neurons. Intracerebroventricular injection of MK-801 or PP2 could reverse the decrease of pain threshold, as well as the up-regulation of Fos-positive neurons in ARC.Conclusions: Peripheral inflammation could activate the neurons in ARC. Among them there were some dopaminergic,β-endorphinergic and glutamatergic neurons. Neuronal activation in ARC by peripheral inflammation was mediated by NMDA receptor, as well as by Src protein tyrosine kinase.