Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

The peripheral corticotropin-releasing factor (CRF)-induced analgesic effect on somatic pain sensitivity in conscious rats: involving CRF, opioid and glucocorticoid receptors.

The corticotropin-releasing factor (CRF) is involved in somatic pain regulation and may produce an analgesic effect in humans and animals, although the mechanisms of the CRF-induced analgesia remain unclear. CRF action is mediated by the CRF receptors of subtypes 1 and 2 (CRF-R1 and CRF-R2, respectively). Activation of the hypothalamic -pituitary -adrenocortical axis (HPA) is provided by CRF-R1; but CRF-R2 are also involved in the regulation of the HPA axis, and, respectively, glucocorticoids, the end hormones of the HPA axis, also participate in somatic pain regulation. Additionally, opioids may contribute to the CRF-induced analgesia. This article serves as an overview of the role of CRF-R1 and CRF-R2, as well as glucocorticoid and opioid receptors in peripheral CRF-induced analgesia in conscious rats, while we focused on the data obtained under normal (non-pathological) conditions including results of our studies in rats. The involvement of CRF-R1 and CRF-R2, glucocorticoids and opioid receptors was studied under the same experimental conditions following pretreatment with appropriate antagonists: NBI 27914, astressin2-B, naltrexone and RU 38486, respectively. Somatic pain sensitivity was measured by the tail flick latencies induced by thermal stimulus (tail flick test). Peripheral administration of the CRF caused both an increase in the tail flick latencies (analgesic effect) and plasma corticosterone levels. Pretreatment with NBI 27914, astressin2-B, naltrexone or RU 38486 attenuated the peripheral CRF-induced analgesia. The results obtained suggest that the peripheral CRF-induced analgesic effect may be mediated through the involvement of CRF-R1 and CRF-R2 as well as opioid and glucocorticoid receptors, including CRF-R2 and opioid receptors within periaqueductal gray matter of the midbrain.