Upregulation of proinflammatory cytokines and nerve growth factor by intraplantar injection of capsaicin in rats

Capsaicin-sensitive primary afferents (CSPA) are known to be involved in nociception and neurogenic inflammation. Extensive research has been devoted to the sensory role of these fibres but less attention has been paid to their local effector function. This study aimed at gaining more insight into the molecular mechanisms underlying the neurogenic inflammation induced by this special group of afferent fibres. Different groups of rats (n = 5 in each group), either naive or subjected to selective ablation of their CSPA, received individual intraplantar injections of saline, capsaicin, its vehicle or capsaicin preceded by its antagonist, capsazepine. Acute tests for nociception were used to assess the variations of the nociceptive thresholds. Variations of the levels of proinflamamtory cytokines and nerve growth factor (NGF) were measured by enzyme-linked immunosorbant assay (ELISA). Intraplantar injection of capsaicin (10 mug in 50 mul) produced a sustained thermal and mechanical hyperalgesia that peaked at 3-6 h and disappeared 24 h following the injection. Similar capsaicin injection in further groups of rats produced an early upregulation of the proinflamamtory cytokines and NGF, which peaked at 30-60 min and returned to control levels within 2-5 h. Similar effects were observed following the application of either capsaicin or intense electrical stimulation on the cut end of the distal portion of the sciatic nerve. The effects of capsaicin were abolished in rats subjected to selective ablation of their CSPA. These results demonstrate that CSPA can simultaneously challenge the immune system through the release of proinflammatory mediators and the central nervous system through nociceptive signalling and can therefore serve as a common afferent pathway to both immune and nervous systems.