Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat

The neurohypophysial oxytocin and arginine vasopressin system is activated in a knee osteoarthritis rat model

“…A previous study reported that optogenetic stimulation of OXT neurones in the pPVN induces selective reduction in the nociceptive action potential discharge in the spinal dorsal horn 65 ; however, no previous studies have confirmed the anti‐nociceptive effects of OXT with the activation of only magnOXT. Our previous studies examining the role of OXT in various pain models have shown that both magnOXT and parvOXT were activated simultaneously 23‐26 ; thus we cannot fully explain why magnOXTs were not activated in the MIA group. However, our data were consistent in that (i) magnOXT was not activated in the MIA group rats as confirmed by both ISH and OXT‐mRFP1 fluorescence microscopy; (ii) OXT‐mRFP1 fluorescence intensity in the PP of the MIA group rats was not increased; and (iii) plasma OXT in the MIA group was not increased.…”

“…The mechanical and thermal nociceptive threshold of ipsilateral hind paws were assessed. For the mechanical nociceptive threshold, a manual von Frey test was carried out with calibrated filaments (North Coast Medical, Morgan Hill, CA, USA) as described previously 25,26,51 . For the thermal nociceptive threshold, a hot plate test (52.5°C) was performed as described previously 52 .…”

“…Fluorescence immunohistochemistry with spinal sections for ionised calcium‐binding adapter molecule‐1 (Iba‐1) and glial fibrillary acidic protein (GFAP), as well as fluorescence microscopy evaluation of Iba‐1 and GFAP‐positive cells in the spinal dorsal horn, was conducted as described previously 24,25 . Lumbar spinal sections were incubated at 4°C for 3 days with a rabbit monoclonal primary anti‐Iba‐1 antibody (dilution 1:2000; catalogue no.…”

“…Because both exogeneous and endogenous OXT/AVP systems play an important role in nociception, we investigated this system in various rat models of pain 21‐26 . OXT and AVP are primarily synthesised in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) in the hypothalamus.…”

Oxytocin‐monomeric red fluorescent protein 1 synthesis in the hypothalamus under osmotic challenge and acute hypovolemia in a transgenic rat line

“…In the present study, OXT synthesis in the hypothalamus under osmotic challenge and acute hypovolemia was investigated in greater detail by analyzing the mRFP1 fluorescence intensity and transcription of mRFP1 gene expression. Our previous reports showed that changes in hypothalamic OXT-mRFP1 levels are significantly exaggerated compared to changes in endogenous OXT levels, and thus the OXT-mRFP1 transgenic rats are a useful animal model for capturing changes in OXT under physiological conditions (Katoh et al, 2014;Nishimura et al, 2019). Indeed, the mRFP1 fluorescence and mRFP1 expression levels showed strong responses under both osmotic challenge and acute hypovolemia.…”