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.
Highlights
The hypothalamo-neurohypophysial system, comprising oxytocin (OXT) and arginine vasopressin (AVP), regulates delivery, lactation, and homeostasis of plasma osmolality and water balance
We evaluated the effects of acute monoarthritis on activation of the OXT/AVP system and hypothalamo-pituitary adrenal (HPA) axis using a carrageenan-induced model of knee arthritis in rats
IHC study revealed that the number of Fos-ir cells in the ipsilateral lamina I and II of the spinal dorsal horn, SON and paraventricular nuclei (PVN) were significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both the SON and PVN were increased in acute mono-arthritic rats
Summary
The hypothalamo-neurohypophysial system, comprising oxytocin (OXT) and arginine vasopressin (AVP), regulates delivery, lactation, and homeostasis of plasma osmolality and water balance. Recent studies suggest that the OXT/AVP system and hypothalamo-pituitary adrenal (HPA) axis are activated by acute/chronic nociceptive stimuli and are involved in the modulation of nociceptive afferent pathways [1,2,3,4,5,6]. To assess the involvement of the OXT/AVP system and HPA axis in common clinical conditions such as knee arthritis, carrageenan-induced knee arthritis in rats was used as a more ethologically valid model. In the present study, we decided to assess the effects of (only) arthritis without any systemic factors using the acute mono-arthritis model induced by carrageenan on the activity of OXT/AVP system as well as the HPA axis in the same animals simultaneously. Acute mono-arthritis was induced by an injection of carrageenan into a single knee in rats. It is assumed that OXT modulates carrageenan-induced acute mono-arthritis
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