Enhanced pharmacological actions of p,p’-methoxyl-diphenyl diselenide-loaded polymeric nanocapsules in a mouse model of neuropathic pain: Behavioral and molecular insights

Abstract

Neuropathic pain is a public health problem and its treatment is a global challenge. The organoselenium compound p,p’-methoxyl-diphenyl diselenide [(OMePhSe)2] has a potential antinociceptive action and its incorporation into nanocapsules improves this action. The current study evaluated if (OMePhSe)2 administration, free or incorporated into nanocapsules, reduces the chronic pain-like behavior induced by the partial sciatic nerve ligation (PSNL) surgery, a neuropathic pain mouse model. It was also investigated the (OMePhSe)2 restorative effect against the increase in inflammatory and apoptotic protein contents at the central nervous system caused by PSNL to mice. Male Swiss mice were subjected to PSNL during 4 weeks and treated with (OMePhSe)2, free or incorporated into nanocapsules, in a single (25mg/kg, i.g.) or repeated administration schedule (25mg/kg, i.g., once a day for seven days). Both treatments reduced mechanical hypernociception induced by PSNL, but the nanoencapsulation increased the (OMePhSe)2 antinociceptive action two-fold in comparison to its free form. PSNL increased the inflammatory protein contents (iNOS, COX-2, NF-κB, IL-1β and TNF-α) and those of bax and clivated PARP, and reduced bcl-2 content, apoptotic proteins, in the mouse cerebral contral lateral cortex. Furthermore, PSNL induced an activation of MAPK pathway (ERK1,2 and p38). The free or nanoencapsulated (OMePhSe)2 repeated administration restored the molecular changes in the protein contents. This study demonstrates the (OMePhSe)2 nanocapsule effectiveness in an animal model of chronic pain.