Neuropeptides and breathing in health and disease.

Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application. Some neuropeptides have been implicated in pathological states, such as obstructive sleep apnea or asthma. This article provides a concise review of the possible role and functions of several selected neuropeptides in the process of breathing in health and disease and in lung pathologies.

Antinociceptive activity of intraperitoneally administered novel and potent anticonvulsive compound, CY-PROLL-SS, in animal neuropathic pain models.

BACKGROUND: Neuropathic pain is still one of the most difficult pain states to be treated due to the lack of effective drugs. Although the mechanism of action of antiepileptic drugs in alleviating neuropathic pain is not fully understood, it is believed that the bases for both diseases are similar pathophysiologic disturbances. Therefore, in this article we explored the analgesic potential of a recently discovered compound CY-PROLL-SS (ADD 408003; 4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-dione) with proved anticonvulsant activity. METHODS: CY-PROLL-SS was delivered to animals systemically to assess the antinociceptive effects either in streptozocin (STZ)-induced diabetic or in chronic constriction injury (CCI) models of neuropathic pain after acute exposure to both thermal and mechanical stimulus. RESULTS: Examined here compound dose-dependently reversed thermal and mechanical hyperalgesia induced by STZ single injection. Similar results were obtained for CCI-induced hyperalgesia; however, in this case an attenuation of thermal and reversal of mechanical hyperalgesia were observed. CONCLUSIONS: High doses of CY-PROLL-SS considerably alleviate peripheral neuropathic pain in model of STZ diabetic neuropathy and CCI. However, mechanisms remain to be elucidated.

Neurotensin-based hybrid peptide's anti-inflammatory activity in murine model of a contact sensitivity response.

The objective of the study was to investigate the possibility of modulation of skin inflammation by topical treatment with a novel compound: an opioid-neurotensin hybrid peptide PK20 encompassing endomorphin-2 analog and modified fragment of neurotensin (8-13). Contact sensitivity response was induced in mice by skin sensitization with dinitrofluorobenzene (DNFB) followed by topical hapten application on ears. Mice were treated locally with PK20 or pure cream 2h after the challenge with DNFB. 2 and 24h after hapten exposure, ear thickness was determined. Ears were collected for histology and homogenization. Supernatants were used for measurement of contents of cytokines and lipid peroxidation products. Treatment with PK20 reduced significantly the late phase of contact sensitivity response, which was revealed by ear thickness diminution and reduction of inflammatory cell infiltration. The average concentrations of IL-1α, MCP-1, TNF-α and thiobarbituric acid-reactive substances were significantly decreased in the ears treated with the chimera in comparison to the control cream treated ears in DNFB sensitized/DNFB challenged group. We found that PK20 topical treatment alleviates hypersensitivity responses triggered by DNFB challenge and usage of the hybrid peptide may be a novel therapeutic strategy in the treatment of chronic inflammatory diseases. However, the mechanism remains unclear and needs further investigation.