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

摘要

Graphical abstract Display Omitted Highlights ? The nanoencapsulation prolonged the (OMePhSe) 2 anti-hypernociceptive action. ? (OMePhSe) 2 reduced the increase in the inflammatory protein contents. ? (OMePhSe) 2 modulated the PSNL-induced MAPK activation. ? (OMePhSe) 2 restored the apoptotic alterations caused by the PSNL. ? (OMePhSe) 2 NC had superior pharmacological action. 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 (ERK 1,2 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.