Chemotherapy-induced
peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient's life. It is characterized by somatosensory alterations, including
chronic pain, and a high risk of suffering
mental disorders such as depression and anxiety. Unfortunately, an effective treatment for this neuropathology is yet to be found. We investigated the therapeutic potential of
cobalt protoporphyrin IX (CoPP), a
heme oxygenase 1 inducer, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate
dichloromethane complex (
GYY4137), a slow
hydrogen sulfide (H2S) donor, in a preclinical model of
paclitaxel (PTX)-induced
peripheral neuropathy (PIPN) in mice. At three weeks after PTX injection, we evaluated the effects of the repetitive administration of 5 mg/kg of CoPP and 35 mg/kg of
GYY4137 on PTX-induced nociceptive symptoms (mechanical and cold
allodynia) and on the associated emotional disturbances (anxiety- and depressive-like behaviors). We also studied the mechanisms that could mediate their therapeutic properties by evaluating the expression of key
proteins implicated in the development of nociception, oxidative stress, microglial activation, and apoptosis in prefrontal cortex (PFC) and dorsal root ganglia (DRG) of mice with PIPN. Results demonstrate that CoPP and
GYY4137 treatments inhibited both the nociceptive symptomatology and the derived emotional alterations. These actions were mainly mediated through potentiation of
antioxidant responses and inhibiting oxidative stress in the DRG and/or PFC of mice with PIPN. Both treatments normalized some plasticity changes and apoptotic reactions, and
GYY4137 blocked microglial activation induced by PTX in PFC. In conclusion, this study proposes CoPP and
GYY4137 as good candidates for treating
neuropathic pain, anxiety- and depressive-like effects of PTX.