In the present study, we investigated possible peripheral antinociceptive effects of low doses of naloxone using both an in vivo and in vitro model of trigeminal nociception. Low doses of naloxone

injected locally into the rat wiskerpad elicited antinociceptive activity in the rat orofacial formalin test. The block of primary afferents with local administration of capsaicin suggested that naloxone acts both directly on sensory neurons and indirectly, by modulating the inflammatory component of the second phase of formalin test. Naloxone analgesia is maintained in rats made tolerant to the p-receptor agonist LY2606368 supplier DAMGO, suggesting the involvement of delta- and kappa-Opioid receptors. Subsequently, the effects of very low doses of naloxone were tested in primary cultures of rat trigeminal neurons activated with bradykinin, in order to elucidate the mechanisms of action underlying naloxone antinociceptive effects. Naloxone inhibited bradykinin-evoked CGRP release in two different experimental paradigms, i.e. primed and unprimed cultures, acting at the level of delta- and kappa-opioids receptors.

These results suggest that low doses of naloxone can directly modulate the activation of the trigeminal neurons by modulating the activity of specific opioid receptors, and this effect may be clinically relevant in combined therapies where an increased Niraparib chemical structure analgesic effect is sought through the potentiation of peripheral mechanisms. (C) 2009 Elsevier Ltd. All rights reserved.”
“Ion channel

stochasticity can influence the voltage dynamics of neuronal membrane, with stronger effects for smaller patches of membrane because of the correspondingly smaller number of channels. We examine this question with respect to first spike statistics in response to a periodic input of membrane patches including stochastic Hodgkin-Huxley channels, comparing these responses to spontaneous firing. Without noise, firing threshold of the model depends on frequency a sinusoidal stimulusis subthreshold for Low-density-lipoprotein receptor kinase low and high frequencies and suprathreshold for intermediate frequencies. When channel noise is added, a stimulus in the lower range of subthreshold frequencies can influence spike output, while high subthreshold frequencies remain subthreshold. Both input frequency and channel noise strength influence spike timing. Specifically, spike latency and jitter have distinct minima as a function of input frequency, showing a resonance like behavior. With either no input, or low frequency subthreshold input, or input in the low or high suprathreshold frequency range, channel noise reduces latency and jitter, with the strongest impact for the lowest input frequencies. In contrast, for an intermediate range of suprathreshold frequencies, where an optimal input gives a minimum latency, the noise effect reverses, and spike latency and jitter increase with channel noise. Thus, a resonant minimum of the spike response as a function of frequency becomes more pronounced with less noise.