Infection with a high dose of the intracellular parasitic protozoan Leishmania major induces a sustained
hyperalgesia in susceptible BALB/c mice accompanied by up-regulation of the pro-inflammatory
cytokines IL-1β and
IL-6.
Interleukin-13 (IL-13) has been shown to reduce this
hyperalgesia (despite increased levels of IL-6) and the levels of IL-1β during and after the treatment period. These findings favor the
cytokine cascade leading to the production of sympathetic
amines (involving TNF-α and KC) over
prostaglandins (involving IL-lβ and IL-6) as the final mediators of
hyperalgesia. The aim of this study was to investigate the effect of daily treatment with the β-blockers
atenolol on L. major-induced
inflammation in mice with respect to
hyperalgesia as well as the levels of TNF-α and KC (the analog of IL-8 in mice). Our data demonstrates that
atenolol is able to reduce the L. major induced sustained peripheral
hyperalgesia, which does not seem to involve a direct role for neither IL-lβ nor KC. Moreover, our results show that TNF-α may play a pivotal and direct role in sensitizing the peripheral nerve endings (nociceptors) since its level was reduced during the period of
atenolol treatment, which correlates well with the reduction of the observed peripheral, but not central,
hyperalgesia. These findings contribute to a better understanding of the
cytokine cascade leading to
hyperalgesia and may lead to the development of new and more efficient medications for many types of
pain.