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

Abstract

Osteoarthritis (OA) causes chronic joint pain and significantly impacts daily activities. Hence, developing novel treatment options for OA has become an increasingly important area of research. Recently, studies have reported that exogenous, as well as endogenous, hypothalamic‐neurohypophysial hormones, oxytocin (OXT) and arginine‐vasopressin (AVP), significantly contribute to nociception modulation. Moreover, the parvocellular OXT neurone (parvOXT) extends its projection to the superficial spinal dorsal horn, where it controls the transmission of nociceptive signals. Meanwhile, AVP produced in the magnocellular AVP neurone (magnAVP) is released into the systemic circulation where it contributes to pain management at peripheral sites. The parvocellular AVP neurone (parvAVP), as well as corticotrophin‐releasing hormone (CRH), suppresses inflammation via activation of the hypothalamic‐pituitary adrenal (HPA) axis. Previously, we confirmed that the OXT/AVP system is activated in rat models of pain. However, the roles of endogenous hypothalamic‐neurohypophysial hormones in OA have not yet been characterised. In the present study, we investigated whether the OXT/AVP system is activated in a knee OA rat model. Our results show that putative parvOXT is activated and the amount of OXT‐monomeric red fluorescent protein 1 positive granules in the ipsilateral superficial spinal dorsal horn increases in the knee OA rat. Furthermore, both magnAVP and parvAVP are activated, concurrent with HPA axis activation, predominantly modulated by AVP, and not CRH. The OXT/AVP system in OA rats was similar to that in systemic inflammation models, including adjuvant arthritis; however, magnocellular OXT neurones (magnOXT) were not activated in OA. Hence, localised chronic pain conditions, such as knee OA, activate the OXT/AVP system without impacting magnOXT.

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat

“…S1 online), and mechanical and thermal hyperalgesia were still observed in the SNL. Although the expression of AVP-eGFP, AVP mRNA, and plasma AVP concentration was significantly increased, hyperalgesia persisted in our previous AA model and knee OA model 20 , 22 . We previously reported that AVP and Oxytocin (OXT) exhibited similar kinetics in various pain models 20 , 21 , 25 .…”

“…AVP-eGFP Tg rats (7 weeks old, weighing 238–305 g) and AVP-hM3Dq-mCherry Tg rats (7 weeks old, weighing 253–350 g) were bred and maintained as described previously 22 , 24 , 51 . All procedures were performed according to the guidelines on the use and care of laboratory animals established by the Physiological Society of Japan.…”

“…The expression kinetics of the AVP system in NP have not been previously studied. We have previously reported increased endogenous AVP expression in formalin-induced inflammation, adjuvant-induced arthritis (AA), acute monoarthritis, and knee osteoarthritis (OA) in AVP-enhanced green fluorescent protein (eGFP) transgenic (Tg) rats 19 – 22 . In AVP-eGFP Tg rats, the activity of AVP neurones can be visualised in vivo and ex vivo without the use of immunohistochemistry by AVP and Fos 23 .…”

Identification of SCRG1 as a Potential Therapeutic Target for Human Synovial Inflammation

“…For the six marker genes previously identified, we found that CDKN1A, FOSB, STMN2, and SLC2A3 genes were reported to be associated with cartilage inflammation in OA (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). For example, the expression level of CDKN1A will increase correspondingly during cartilage degeneration (44), IL-17 and IL-1beta induced collagenase-3 production through AP-1 occurred with differential protein complex, and stimulation resulted in FOSB activation (52), STMN2 has significant differences between preserved and subchondral bone (48).…”

Transgenic approaches to opening up new fields of vasopressin and oxytocin research

“…UETA their fluorescence intensities in the soma and number of fluorescent terminals are increased sensitively after physiological and pathophysiological stimuli such as dehydration, 13 chronic salt loading, 32 seizure, 33,34 acute/chronic nociceptive stimuli, [35][36][37][38][39][40][41][42] aging 43 and estrus cycle. 44 In addition, it is known that corticotropin-releasing homrone (CRH)-producing parvocellular neurons in the PVN also synthesize AVP under stressful conditions.…”