Protectin DX reduces inflammatory pain initiated by superoxide anion in mice: targeting leukocyte recruitment, oxidative stress, cytokine production and TRPV1+ nociceptive sensory neuron activation.

OBJECTIVE AND

DESIGN

This study investigated the antinociceptive potential and mechanisms of Protectin DX (PDX) in a KO2-induced inflammatory pain.

TREATMENT: Male mice received PDX (1, 3, or 10 ng) or vehicle (0.7% ethanol in sterile saline) intraperitoneally (i.p.), 1 h before KO2 (30 µg intraplantar [i.pl.] or 1 mg [i.p.]).

METHODS

Upon KO2 injection, evoked (mechanical and thermal hyperalgesia, and mechanical allodynia) and non-evoked pain behaviors (weight distribution and overt pain-like behaviors), immune cell recruitment (histopathology and immunofluorescence), cytokine production (ELISA), ROS production (NBT assay), antioxidant capacity (ABTS, FRAP, GSH and catalase assays), TRPV1, and neuronal activation (immunofluorescence and calcium imaging) and toxicity parameters (ALT, AST, urea, creatinine and myeloperoxidase assays) were investigated. Motor performance, mechanical and thermal hyperalgesia were also evaluated without the KO2 injection.

RESULTS

PDX reduced evoked and non-evoked pain, leukocyte recruitment, production of pro-inflammatory cytokines (TNF-α and IL-1β), and oxidative stress. PDX inhibited TRPV1 activity, resulting in inhibition of nociceptive neuron activation. PDX did not alter the plasma levels of ALT, AST, urea, and creatinine, or stomach myeloperoxidase activity. Also, PDX did not affect the basal mechanical and thermal sensitivity and motor activity.

CONCLUSION

PDX inhibits superoxide anion-triggered pain and inflammation, through anti-inflammatory, antioxidant, and neuronal component modulation mechanisms.