oxytocin and Visceral-Pain

Activation of neurons containing oxytocin and corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus, the anterior cingulate cortex (ACC), and the central nucleus of the amygdala (CeA) during colorectal distention (CRD) is likely to play a crucial role in animal models of irritable bowel syndrome (IBS). Earlier studies in rodents showed that the microbiome is involved in social behavior via oxytocin expression in the brain. However, the detailed mechanism of visceral sensation and oxytocin is largely unknown. We tested the following hypotheses: (1) that oxytocin neurons in the PVN are activated by CRD, and (2) that the activation of oxytocin neurons by CRD is related to anxiety-like behavior, visceral perception, and an activation of CRH CeA neurons or ACC neurons. Oxytocin antagonist caused visceral hypersensitivity and anxiety-like behavior. In the PVN, oxytocin neurons were activated by CRD. Noxious CRD activated the CeA, basolateral nucleus of the amygdala (BLA), and ACC. High-dose oxytocin antagonist suppressed ACC activity and activated CRH CeA neurons. These results support our hypotheses. Oxytocin likely regulates CRH CeA neurons in an inhibitory manner and the ACC in an excitatory manner. Further research into the interaction of oxytocin and CRH in visceral pain and anxiety is warranted.

Topics: Animals; Central Amygdaloid Nucleus; Colorectal Neoplasms; Corticotropin-Releasing Hormone; Mice; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Visceral Pain

It is widely hypothesized that menstrual pain is triggered by prostaglandin synthesis that evokes high-pressure uterine contractions and ischemia. However, the effects of molecules implicated in menstrual pain on uterine contractility, perfusion, and oxygenation in vivo have been rarely demonstrated. Studies in women that do not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) have reported elevated levels of platelet-activating factor (PAF). To establish in vivo evidence of PAF's capability to impair uterine homeostasis and to elicit visceral pain, we examined the effects of the PAF receptor agonist (carbamyl PAF [CPAF]) in comparison to other molecules hypothesized to play a role in uterine pain in mice. Uterine pressure was increased by oxytocin, prostaglandin F2α (PGF2α), and CPAF. Even in the absence of inflammatory molecules, uterine contractions reduced uterine oxygenation by 38%. CPAF reduced uterine perfusion by 40% ± 8% and elicited further oxygen desaturation approaching hypoxia (9.4 ± 3.4 mm Hg Pao

Topics: Animals; Dinoprost; Female; Hyperalgesia; Hypoxia; Mice; Mice, Knockout; Oxytocin; Perfusion; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, G-Protein-Coupled; Uterine Contraction; Uterus; Visceral Pain

Visceral hypersensitivity (VH) is a significant contributor to irritable bowel syndrome (IBS). Oxytocin (OT) possesses analgesic effects on the central nervous system (CNS) and attenuates microglial activation, however, little is known about its peripheral effects and involvement in VH of IBS. Reactive enteric glial cells (EGCs) contributes to abnormal motility in gastrointestinal (GI) diseases. The aim of this study was to evaluate the peripheral use of OT to maintain VH and activation of EGCs through involvement of the Toll-like receptor (TLR) 4/MyD88/NF-κB signaling. After assessing a baseline visceromotor response (VMR) to colorectal distension (CRD), rats were exposed to a 1h water avoidance stress (WAS) session. Before each WAS session, intraperitoneal injection of OT (1mg/kg body weight, in phosphate-buffered saline (PBS)) atosiban (0.5mg/kg body weight, in PBS) or PBS (as a vehicle control, 1ml/kg body weight) was administered. Animas are killed 24h after the last WAS session. EGCs activity, relative OT receptor expression, glial fibrillary acidic protein (GFAP) expression and TLR4/MyD88/NF-κB signaling were evaluated. Neonatal maternal separation (MS) significantly increased the OT receptor expression and enhanced VMR to CRD. WAS improved VMR to CRD only during neonatal MS. OT treatment prevented WAS-induced higher VMRs to CRD, which was reversed by an OT receptor antagonist administration. Compared to the vehicle, OT pre-treated rats reduced EGCs activation, GFAP expression and TLR4/MyD88/NF-κB signaling. We conclude that neonatal MS induces VH and visceral pain in rats. Furthermore, exogenous OT attenuated stress-induced VH and EGCs activation, which was mediated by TLR4/MyD88/NF-κB signaling.

Topics: Animals; Colon; Cytokines; Female; Hypothalamus; Inflammation; Maternal Deprivation; Myeloid Differentiation Factor 88; Neuroglia; NF-kappa B; Oxytocin; Pituitary-Adrenal System; Pregnancy; Rats; Rats, Sprague-Dawley; Signal Transduction; Stress, Psychological; Toll-Like Receptor 4; Visceral Pain