Avaliação do efeito da crotoxina conjugada a sílica nanoestruturada SBA-15 na dor crônica: aspectos imunomodulatórios, anti-inflamatórios e antinociceptivos

Abstract

Chronic pain is among the most disabling and costly afflictions, has a negative effect on physical and psychological health, daily activities, employment and economic well-being, being recognised as an important healty public problematic. Chronic pain is characterized by sensorial alterations (hyperalgesia and allodynia) and other symptoms such as lethargy, depression and anxiety. These sickness behaviours with chronic pain are suggestive of a subjacent immune activity. The persistent pain is often associated with some other disease, such as multiple sclerosis [MS], an example of autoimmune disorder. MS is one of the most common neurological disorders diagnosed in young adults; this neuroinflammatory autoimmune disease have common symptoms such as, fatigue, visual impairment, sensory impairment, weakness, urinary dysfunction, spasticity, incoordination, cognitive dysfunction and pain. Despite the advances in research related to chronic pain and multiple sclerosis, the treatments still presenting great difficulties, since that the administration of pharmacos there is no complete reversal of symptoms or cure. Moreover, there are continual reports of patients suffering from their undesirable adverse effects. Therefore, it is necessary to study new drugs for the treatment of these pathologies. It is known that the crotoxin (CTX) despite the toxic effect, in low doses, presents immunomodulatory, anti-inflammatory, antitumor and antinociceptive effect, revealing its potential for the clinical treatment of several pathologies. It is also known that the nanostructured SBA-15 silica, a protective vehicle of biomolecules, may decrease toxicity and increase the immune response to distinct immunogens including vaccins. Thus, the objective of this study was to evaluate whether crotoxin, when conjugated to SBA-15, has its toxic effect reduced and its antinociceptive e immunomodulatory effect enhanced, evaluating its interference on the inflammatory response in the Partial Injury models of the Sciatic Nerve (PSNL) and Experimental Autoimmune Encephalomyelitis (EAE). The results show that the CTX:SBA-15 complex has analgesic effect in both models of chronic pain and reduces the incidence and intensity of clinical signs (motor defict) induced by the EAE model. Further, the treatment with the complex modulates neuroinflammation by reducing the expression of glial cell markers and the expression of proinflammatory cytokines in the CNS. Summarizing, the present work expands the knowledge of the effect of CTX, silica SBA-15 and complex CTX:SBA-15, showing that silica has a protective mechanism, which allows the use of oral CTX. Our data also significantly increase the possibilities of using silica, demonstrating its capacity as a protective vehicle for drugs.