Acute Mono-Arthritis Activates the Neurohypophysial System and Hypothalamo-Pituitary Adrenal Axis in Rats

Abstract

Various types of acute/chronic nociceptive stimuli cause neuroendocrine responses such as activation of the hypothalamo-neurohypophysial [oxytocin (OXT) and arginine vasopressin (AVP)] system and hypothalamo-pituitary adrenal (HPA) axis. Chronic multiple-arthritis activates the OXT/AVP system, but the effects of acute mono-arthritis on the OXT/AVP system in the same animals has not been simultaneously evaluated. Further, AVP, not corticotropin-releasing hormone (CRH), predominantly activates the HPA axis in chronic multiple-arthritis, but the participation of AVP in HPA axis activation in acute mono-arthritis remains unknown. Therefore, we aimed to simultaneously evaluate the effects of acute mono-arthritis on the activity of the OXT/AVP system and the HPA axis. In the present study, we used an acute mono-arthritic model induced by intra-articular injection of carrageenan in a single knee joint of adult male Wistar rats. Acute mono-arthritis was confirmed by a significant increase in knee diameter in the carrageenan-injected knee and a significant decrease in the mechanical nociceptive threshold in the ipsilateral hind paw. Immunohistochemical analysis revealed that the number of Fos-immunoreactive (ir) cells in the ipsilateral lamina I-II of the dorsal horn was significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both sides of the supraoptic (SON) and paraventricular nuclei (PVN) was increased in acute mono-arthritic rats. in situ hybridization histochemistry revealed that levels of OXT mRNA and AVP hnRNA in the SON and PVN, CRH mRNA in the PVN, and proopiomelanocortin mRNA in the anterior pituitary were also significantly increased in acute mono-arthritic rats. Further, plasma OXT, AVP, and corticosterone levels were significantly increased in acute mono-arthritic rats. These results suggest that acute mono-arthritis activates ipsilateral nociceptive afferent pathways at the spinal level and causes simultaneous and integrative activation of the OXT/AVP system. In addition, the HPA axis is activated by both AVP and CRH in acute mono-arthritis with a distinct pattern compared to that in chronic multiple-arthritis.

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

“…We randomly divided the experimental rats into three groups (n = 5‐6 per group): Group A (Control): without any intra‐articular (IA) injection, administered anaesthesia; Group B (Saline): administered 0.05 mL of saline IA injection; and Group C (MIA): administered an IA injection of MIA (1 mg/0.05 mL per joint; Sigma, St Louis, MO, USA) in saline. NaCl or MIA IA injections were administered into the right hind knee joint as described previously 26 …”

“…To evaluate knee OA, three‐dimensional micro‐computed tomography (CT) images and gross images of the right knee joint were taken. In addition, ipsilateral knee transverse diameters were determined to assess knee joint swelling using a digital caliper, as described previously 26 . As a baseline, ipsilateral knee transverse diameters were also determined before IA injection.…”

“…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 .…”

“…Tissue preparation for FIHC and fluorescence microscopy of transgenic rats was conducted as described previously 26,44 . Following i.p.…”

“…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.…”