No abstract

No abstract

Of the sixty-six cells tested with both peptides at 10-7 M, sixteen showed similar responses to both and fifteen showed no response to either: twenty cells showed a greater response to AVP and fifteen a greater response to OXT. Of six phasic firing cells, two showed excitatory responses to AVP and all four cells tested did not show any response to OXT. 4. The dose-dependence of the response to AVP and OXT was tested in six p.v.n. cells. There was a direct relationship between peptide concentration and increased firing rate. The threshold concentration of the peptides ranged from 10-8 to 10-1o M.5. The cells responsive to the peptides were not located in particular areas of the p.v.n. but were diffusely distributed throughout the nucleus.6. After blocking synaptic transmission with a low Ca2+ and high Mg2+ medium, all tested cells (AVP, n = 15; OXT, n = 14) which had responded to applications of AVP or OXT in normal medium still showed responses to the peptides, although the effect was less marked in half the cells. However, in the absence of synaptic transmission two cells showed unimpaired responses to one ofthe peptides but greatly depressed responses to the other. 9. We conclude that p.v.n. cells were sensitive to AVP and OXT, probably through specific receptors for each peptide: for AVP, the receptor was probably of the V1 type.

There were significant associations between serum cortisol level, including cortisol/DHEAS ratio, and periodontitis severity in elderly subjects who had never smoked.

In many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism in oral ulcerative mucositis after chemotherapy has not been extensively studied. In this study, we investigated spontaneous pain and mechanical allodynia in a preclinical model of oral ulcerative mucositis after systemic administration of the chemotherapy drug 5-fluorouracil, using our proprietary pain assay system for conscious rats. 5-Fluorouracil caused leukopenia but did not induce pain-related behaviors. After 5-fluorouracil administration, oral ulcers were developed with topical acetic acid treatment. Compared with saline-treated rats, 5-fluorouracil-exposed rats showed more severe mucositis with excessive bacterial loading due to a lack of leukocyte infiltration, as well as enhancements of spontaneous pain and mechanical allodynia. Antibacterial drugs, the lipid A inhibitor polymyxin B and the TRPV1/TRPA1 channel pore-passing anesthetic QX-314, suppressed both the spontaneous pain and the mechanical allodynia. The cyclooxygenase inhibitor indomethacin and the TRPV1 antagonist SB-366791 inhibited the spontaneous pain, but not the mechanical allodynia. In contrast, the TRPA1 antagonist HC-030031 and the N-formylmethionine receptor FPR1 antagonist Boc MLF primarily suppressed the mechanical allodynia. These results suggest that 5-fluorouracil-associated leukopenia allows excessive oral bacterial infection in the oral ulcerative region, resulting in the enhancement of spontaneous pain through continuous TRPV1 activation and cyclooxygenase pathway, and mechanical allodynia through mechanical sensitization of TRPA1 caused by neuronal effects of bacterial toxins. These distinct pain mechanisms explain the difficulties encountered with general treatments for oral ulcerative mucositis-induced pain in patients with cancer and suggest more effective approaches.