Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis) causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs) are expressed in pain-relevant loci (dorsal root ganglia, DRG), which suggests their possible involvement in nociception, but their functions in pain remain unclear.</p> <p>Results</p> <p>In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA). In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1) was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function.</p> <p>Conclusion</p> <p>Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after inflammation may not only directly activate proton-sensing ion channels (such as TRPV1) to cause pain but also act on proton-sensing GPCRs to regulate the development of hyperalgesia.</p

Trans fatty acids in milk fat

The trans fatty acids in milk fat from the indoor feeding ( March, April) and the pasture feeding period (May) were determined. An argentation thin layer chromatography (Ag-TLC) and gas liquid chromatography (GLC) on a polar capillary column (CP Sil 88) were used.The content of trans fatty acids in milk fat showed considerable seasonal variations. The trans 18:1 content for the pasture period was 5.73 g/100 g milk fat (MF) and only 1.83 g/100 g MF for the indoor feeding period. About one-half of trans 18:1 isomers in the samples from the indoor feeding period and more than 60% in the samples from May was trans-11 18:1 acid. The level of two trans 18:2 isomers (cis-trans and trans-cis) was about 4 times higher (0.81 g/100 g MF) in the pasture feeding period than in the indoor feeding period (0.18 g/100 g MF).Przedmiotem badań byla zawartość kwasów tłuszczowych trans w tłuszczu mleka z okresu żywienia oborowego (marzec, kwiecień) i okresu żywienia pastwiskowego (maj). Oznaczenia przeprowadzano metodą chromatografii gazowej (GLC) na polarnej kolumnie kapilarnej (CP Sil 88) w połączeniu z metodą chromatografii cienkowarstwowej z azotanem srebra (Ag-TLC). Zawartość izomerów trans w tłuszczu mleka wykazywała znaczne wahania sezonowe. W okresie żywienia oborowego łączna zawartość izomerów trans 18:1 wynosiła 1,83 g/100 g tłuszczu, a w okresie żywienia pastwiskowego 5,73 g/100 g (tab. 1). Około 50% izomerów trans w tłuszczu z okresu żywienia oborowego i ponad 60% w tłuszczu mleka uzyskanego w maju stanowił izomer trans-11 18:1 (tab. 2). Zawartość izomerów trans kwasu 18:2 (cis-trans i trans-cis) była ponad czterokrotnie wyższa w tłuszczu mleka z okresu żywienia pastwiskowego (0,81 g/100 g tłuszczu) w porównaniu z tłuszczem mleka z okresu żywienia oborowego (tab. 4)