5-FLUORO-2-OXINDOLE TREATMENT INHIBITED NEUROPATHIC PAIN AND THE EMOTIONAL DISORDERS ASSOCIATED AND ENHANCED THE LOCAL ANTINOCICEPTIVE EFFECTS OF MORPHINE

P. Ferreira-Chamorro1,2, A. Redondo1,2, G. Riego1,2, O. Pol1,2 

1Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Grup de Neurofarmacologia Molecular, Barcelona, Spain, 2Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Background and aims: Persistent neuropathic pain is associated with anxiety and depressive-like behaviors which treatment is not completely resolved. Therefore, the research of new treatments is indispensable. We studied if the administration of 5-fluoro-2-oxindole (FLUO) could inhibit the nociceptive responses and emotional disorders accompanying neuropathic pain and increase the antinociceptive effects of morphine.
Methods: In C57BL/6 male mice with neuropathic pain, anxiety- and depressive-like behaviors caused by the chronic constriction of sciatic nerve (CCI) we evaluated the antinociceptive, anxiolytic and antidepressant effects of the intraperitoneal administration of FLUO and its effects on the local antinociceptive actions of morphine. The protein levels of NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1) and μ opioid receptors (MOR) in the spinal cord at 28 days after CCI were also evaluated.
Results: Our results showed that FLUO inhibited the mechanical allodynia, thermal hyperalgesia and thermal allodynia induced by CCI as well as the anxiety and depression-like behaviors associated with neuropathic pain. The administration of FLUO also increased the local analgesic effects of morphine. This treatment increased the expression of NQO1 and normalized the down regulation of HO-1 and MOR induced by CCI in the spinal cord.
Conclusions: This study reveals that treatment with FLUO alone and/or combined with morphine might be an interesting strategy for the treatment of persistent neuropathic pain and comorbidities associated.

This work was supported by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Madrid, Spain and Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea [Grant: PI1800645].

5-FLUORO-2-OXINDOLE TREATMENT INHIBITED NEUROPATHIC PAIN AND THE EMOTIONAL DISORDERS ASSOCIATED AND ENHANCED THE LOCAL ANTINOCICEPTIVE EFFECTS OF MORPHINE