As a neurohormone and as a neurotransmitter, oxytocin has been implicated in the stress response. Descending oxytocin‐containing fibres project to the dorsal horn of the spinal cord, an area important for processing nociceptive inputs. Here we tested the hypothesis that oxytocin plays a role in stress‐induced analgesia and modulates spinal sensory transmission. Mice lacking oxytocin exhibited significantly reduced stress‐induced antinociception following both cold‐swim (10 °C, 3 min) and restraint stress (30 min). In contrast, the mice exhibited normal behavioural responses to thermal and mechanical noxious stimuli and morphine‐induced antinociception. In wild‐type mice, intrathecal injection of the oxytocin antagonist dOVT (200 μm in 5 μl) significantly attenuated antinociception induced by cold‐swim. Immunocytochemical staining revealed that, in the mouse, oxytocin‐containing neurones in the paraventricular nucleus of the hypothalamus are activated by stress. Furthermore, oxytocin‐containing fibres were present in the dorsal horn of the spinal cord. To test whether descending oxytocin‐containing fibres could alter nociceptive transmission, we performed intracellular recordings of dorsal horn neurones in spinal slices from adult mice. Bath application of oxytocin (1 and 10 μm) inhibited excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. This effect was reversed by the oxytocin antagonist dOVT (1 μm). Whole‐cell recordings of dorsal horn neurones in postnatal rat slices revealed that the effect of oxytocin could be blocked by the addition of GTP‐γ‐S to the recording pipette, suggesting activation of postsynaptic oxytocin receptors. We conclude that oxytocin is important for both cold‐swim and restraint stress‐induced antinociception, acting by inhibiting glutamatergic spinal sensory transmission.

To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

Our data implicate epigenetic dysregulation of a host of genes in KBD and OA. Furthermore, we observed common causal epigenetic changes shared by KBD and OA.

No abstract