Targeting NGF system to fight neuropathic pain behavioral and immunohistochemical evidence in mice

Background and Aims: it has been demonstrated that the anti-NGF αD11 and the anti-TrkA MNAC13 counteract neuropathic pain in mice. The aim of this study was to evaluate the duration of the action of the two antibodies and the structural and morphological alterations induced in central and peripheral nervous system. Methods: Chronic Constriction Injury (CCI) of the sciatic nerve was performed in C57BL/6J mice. Mice were administered with αD11 or MNAC13 (70 or 100 µg/mouse/day) from day 3 until day 10 post-CCI. Analgesic effects were tested through Dynamic Plantar Aesthesiometer from day 3 to day 90. Spinal cords and sciatic nerves were collected at D3, D11, D24 and D90 for immunohistochemistry. Results: αD11 and MNAC13 induce significant dose- and time-dependent analgesic effects: the antiallodynic effect was still present at D90 following the highest doses of both antibodies. Immunohistochemical analysis show significant differences in inflammatory and myelination markers between treated and control animals, treated animals showing reduced glial and mast cells activation and a better nerve regeneration. Conclusions: Data obtained prove that: i) the analgesic effect of the antibodies αD11 and MNAC13 are extremely long-lasting, being observable more than two months after the end of the treatment and ii) the antiNGF and antiTrkA antibodies reduce inflammation and facilitate the regenerative processes. Therefore, our results strongly support the importance of considering the NGF system in the development of novel therapies to modulate and control neuropathy.