Protein kinase C (PKC) is able to phosphorylate several cellular components that serve as key regulatory components in signal transduction pathways of nociceptor excitation and sensitisation. Therefore, the present study attempted to assess some of the mechanisms involved in the overt nociception elicited by peripheral administration of the PKC activator, phorbol 12-myristate 13-acetate (PMA), in mice. The intraplantar (i.pl.) injection of PMA (16-1600 pmol/paw), but not its inactive analogue alpha-PMA, produced a long-lasting overt nociception (up to 45 min), as well as the activation of PKCalpha and PKCepsilon isoforms in treated paws. Indeed, the local administration of the PKC inhibitor GF109203X completely blocked PMA-induced nociception. The blockade of NK1, CGRP, NMDA, beta1-adrenergic, B2 or TRPV1 receptors with selective antagonists partially decreased PMA-induced nociception. Similarly, COX-1, COX-2, MEK or p38 MAP kinase inhibitors reduced the nociceptive effect produced by PMA. Notably, the nociceptive effect promoted by PMA was diminished in animals treated with an antagonist of IL-1beta receptor or with antibodies against TNFalpha, NGF or BDNF, but not against GDNF. Finally, mast cells as well as capsaicin-sensitive and sympathetic fibres, but not neutrophil influx, mediated the nociceptive effect produced by PMA. Collectively, the results of the present study have shown that PMA injection into the mouse paw results in PKC activation as well as a relatively delayed, but long-lasting, overt nociceptive behaviour in mice. Moreover, these results demonstrate that PKC activation exerts a critical role in modulating the excitability of sensory neurons.

No abstract

These results indicate that the BV from Apis melifera causes a marked dose-and time-dependent oedema formation in the rat paw, an effect that is accompanied by intense leukocyte migration. The pro-inflammatory response induced by BV is mediated by several mechanisms, namely the release of histamine and/or serotonin from mast cells, activation of H1 histamine receptor, production of nitric oxide, the involvement of kinins through the activation of B1 and B2 receptors, and also tachykinins acting at NK1 receptor or and to a lesser extent at NK2 and NK3 receptors.