Abstract <p>The hypothalamic paraventricular nucleus (PVN) is a key neuroendocrinebrain center involved in the regulation of pain sensitivity. Itsdysfunction is associated with the development of intestinal hyperalgesia(increased pain sensitivity), which underlies the pathogenesis ofboth post-inflammatory and stress-induced chronic abdominal painsyndromes. However, the disorders in the neuronal mechanisms of PVN-mediatedcontrol over visceral nociception that contribute to the developmentof intestinal hyperalgesia of various etiologies remain unclear. Thisstudy was aimed to comparatively assess changes in the functionalproperties of visceral pain-responsive PVN neurons associated withpost-inflammatory or post-stress enhancement of intestinal painsensitivity. Experiments were carried out on three groups of adultmale Wistar rats: (1) controls (without adverse exposures), (2)those exposed to intestinal inflammation (colitis), and (3) those exposedto combined traumatic stress. In awake rats of all groups, intestinalpain sensitivity was assessed by electromyographic recording ofthe visceromotor response to noxious colorectal distension (CRD), whilebackground and CRD‑evoked activity of PVN neurons was recorded bymicroelectrodes under general anesthesia (a mixture of urethaneand α-chloralose, i.p.). It was found that a significant increase inintestinal pain sensitivity, induced by colitis, is associated witha general decrease in the firing rate of PVN neurons and an increasein their inhibition during noxious CRD. In turn, in less pronounced intestinalhyperalgesia induced by traumatic stress, the PVN exhibits an increasein general neuronal activity and an attenuation of local inhibitorynociceptive neurotransmission during noxious CRD. The revealed differencesin the hypothalamic mechanisms of post-inflammatory and post-stressintestinal hyperalgesia may determine the specificity of their neuroendocrineaccompaniment and serve as potential targets for differentiatedtreatment of such conditions in the clinic.</p>