Avaliação do efeito central da crotalfina na neuropatia periférica induzida em camundongos

Abstract

Pain is considered a public health problem. Estimates suggest that 20º/o of the adult worldwide population suffers from different types of pain. Particularly in relation to chronic pain, it may have inflammatory origin and I or to be due to nerve damage, altering the functionality of the sensory system (nociception) as well as the neuroimmune interface. Despite the advances of the research in this field, the treatment of pain still presents great difficulties, since even with the administration of the medicines clinically available, many patients report an incomplete reversal of the painful state and undesirable adverse effects. Crotalphine (CRO) is a synthetic peptide produced from the sequence of the natural analgesic factor isolated from the venom of the Crotalus durissus terrificus snake that induces potent and long-lasting antinociceptive effect in acute and chronic pain models. ln relation to its peripheral effect, it is known that it occurs by the release of endogenous opioids, particularly dynorphin A, and this release is dependent on the activation of cannabinoid type 2 receptors. ln the present work we demonstrate that the central analgesic effect of crotalphine involves participation of mu, kappa and delta opioid receptors as well as endogenous opioids release in addition to dynorphin A, such as met-enkephalin and beta-endorphin. ln addition, our data demonstrated the participation of CB1 and CB2 cannabinoid receptors in this effect, but there is no endocannabinoids involvement. We also verified that resident cells of the central nervous system, particularly microglia, play an important role in the central analgesic effect, and that crotalphine also reduces the release of interleukin 6 (IL-6), reinforcing its effect on the inflammatory response.