ASIC3 in the cerebrospinal fluid-contacting nucleus of brain parenchyma contributes to inflammatory pain in rats

Objective: The study explores the role of acid-sensitive ion channel 3 (ASIC3) in the cerebrospinal fluid (CSF)-contacting nucleus of the parenchyma of rat brain, in inflammatory pain. Methods: We injected rats subcutaneously with complete Freund's adjuvant (CFA) into the plantar surface of the left hind paw. We then measured the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT). After horseradish peroxidase-conjugated toxin subunit B (CB-HRP) retrograde tracing of one of the rats' lateral ventricles, we used immunohistochemistry, to observe the distribution and expression of ASIC3 in CSF-contacting nucleus with double labeling of CB-HRP and ASIC3. We injected a selective ASIC3 antagonist, APETx2, into one of the rat's lateral ventricles, to test for inhibition of ASIC3 activation and the effects on heat and mechanical hyperalgesia, in response to inflammation. Results: The CSF-contacting nucleus is always located in a specific region of parenchyma in rat brain, consistent with previous findings. The CSF-contacting nucleus has ASIC3, which increased significantly in persistent inflammation following injection of CFA. The intracerebroventricular injection (ICV) administration of specific ASIC3 antagonist APETx2 suppressed the heat and mechanical hyperalgesia following CFA injection. Conclusion: The CSF-contacting nucleus regulates inflammatory pain in the central nervous system (CNS) via increased expression of ASIC3, providing a new molecular basis for pain transmission and regulation.