No abstract

Peripheral inflammatory hyperalgesia depends on the sensitization of primary nociceptive neurons. Inflammation drives molecular alterations not only locally but also in the dorsal root ganglion (DRG) where interleukin-1 beta (IL-1β) and purinoceptors are upregulated. Activation of the P2X7 purinoceptors by ATP is essential for IL-1β maturation and release. At the DRG, P2X7R are expressed by satellite glial cells (SGCs) surrounding sensory neurons soma. Although SGCs have no projections outside the sensory ganglia these cells affect pain signaling through intercellular communication. Therefore, here we investigated whether activation of P2X7R by ATP and the subsequent release of IL-1β in DRG participate in peripheral inflammatory hyperalgesia. Immunofluorescent images confirmed the expression of P2X7R and IL-1β in SGCs of the DRG. The function of P2X7R was then verified using a selective antagonist, A-740003, or antisense for P2X7R administered in the L5-DRG. Inflammation was induced by CFA, carrageenan, IL-1β, or PGE 2 administered in rat's hind paw. Blockage of P2X7R at the DRG reduced the mechanical hyperalgesia induced by CFA, and prevented the mechanical hyperalgesia induced by carrageenan or IL-1β, but not PGE 2. It was also found an increase in P2X7 mRNA expression at the DRG after peripheral inflammation. IL-1β production was also increased by inflammatory stimuli in vivo and in vitro, using SGC-enriched cultures stimulated with LPS. In LPS-stimulated cultures, activation of P2X7R by BzATP induced the release of IL-1β, which was blocked by A-740003. In summary, our data suggest that peripheral inflammation leads to the activation of P2X7R expressed by SGCs at the DRG. Then, ATP-induced activation of P2X7R mediates the release of IL-1β from SGC. This evidence places the SGC as an active player in the establishment of peripheral inflammatory hyperalgesia and highlights the importance of the events in DRG for the treatment of inflammatory diseases.

Respostas cardiorrespiratória e metabólica do propofol nas formulações em emulsão lipídica ou microemulsão em gatas.Ciência Rural, v.43, n.8, ago, 2013. 1435Respostas cardiorrespiratória e metabólica do propofol nas formulações em emulsão lipídica ou microemulsão em gatas 40,6±30,7; 91±37,5; 134,5±54,5 e 169,1±55,4 minutos no MICRO e de 68,8±37,3; 133,3±85,3; 171,3±77,1 e 233,1±60,6 40.6±30.7, 91±37.5, 134.5±54.5 and 169.1±55.4 minutes in MICRO and 68.8±37.3, 133.3±85.3, 171.3±77.1 and 233.1±60.6

In this study, we used Raman spectroscopy as a new tool to investigate pathological conditions at the level of chemical bond alterations in biological tissues. Currently, there have been no reports on the spectroscopic alterations caused by diabetic neuropathy in the dorsal root ganglia (DRG). DRG are a target for the treatment of neuropathic pain, and the need for more effective therapies is increasing. Photobiomodulation therapy (PBMT) through infrared low-level laser irradiation (904 nm) has shown analgesic effects on the treatment of neuropathy. Thus, the aim of this study was to use Raman spectroscopy to characterize the spectral DRG identities of streptozotocin (STZ)-induced diabetic neuropathic (hyperalgesic) rats and to study the influence of PBMT over such spectra. Characteristic DRG peaks were identified at 2704, 2850, 2885, 2940, 3061 and 3160 cm −1 , whose assignments are CH 2 /CH 3 symmetric/asymmetric stretches, and C─H vibrations of lipids and proteins. DRG from hyperalgesic rats showed an increased normalized intensity of 2704, 2850, 2885 and 3160 cm −1 . These same peaks had their normalized intensity reduced after PBMT treatment, accompanied by an anti-hyperalgesic effect. Raman spectroscopy was able to diagnose spectral alterations in DRG of hyperalgesic rats and the PBMT reduced the intensity of hyperalgesia and the altered Raman spectra. K E Y W O R D Sdiabetic neuropathy, dorsal root ganglia, hyperalgesia, photobiomodulation, Raman spectroscopy

RESUMO Os felinos são defi cientes na biotransformação do propofol e os dados em relação à farmacocinética nessa espécie 2, 5, 10, 15, 30 e 60 minutos de infusão e aos 5, 10, 15, 30, 60, 90, 120, 180, 240, 360, 600 2, 5, 10, 15, 30, and 60 minutes of infusion and at 5, 10, 15, 30, 60, 90, 120, 180, 240, 360, 600 and 1440

ABSTRACT

RESUMO O propofol em nanoemulsão é uma nova formulação constituída por sistemas nanoemulsionados, caracterizado pela ausência do veículo lipídico. A modifi cação do veículo pode 2, 5, 10, 15, 30, and 60 minutes after the bolus dose, and after the end of the infusion at fi ve, 10, 15, 30, 60, and 90 minutes and 2, 3, 4, 6, 10, and 24 hours. There were no signifi cant differences in the evaluated pharmacokinetics parameters that included volume of distribution, clearance, elimination rate constant, half-life, and distribution constants, demonstrating that propofol nanoemulsion has no pharmacokinetics differences when compared to the traditional formulation.

Inflammation is a defense response against human death by physical, chemical or biological agents, which triggers, among other factors, pain. Despite being a warning and protection signal, it decreases the life quality.In view of this, research into new antinociceptive therapeutic options is necessary. As it was verified that the keratinocytes of the basal stratum of the epidermis release endogenous opioid, being an important antinociceptive mechanism, the best understanding of the relationship between peripheral nervous system, skin (keratinocytes) and analgesia is important.Thus, the present study aims to evaluate the analgesic potential of culture supernatant of human keratinocytes in the experimental model of inflammatory hyperalgesia. The purpose of it is to establish the anti-hyperalgesic mechanism and time of action, which may bring a new way of local treatment of inflammatory hyperalgesia.