Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain

Abstract EN

Neuropathic pain is a growing healthcare problem causing a global burden.

Currently used analgesics such as opioids are associated with adverse effects; urging the need for safer alternatives.

Here we aimed to investigate the potential analgesic effects of tesaglitazar; dual peroxisome proliferator-activated receptors α and γ (PPARα and γ) agonist in rat models of neuropathic pain.

This study also aimed to investigate the modulation of the transient receptor potential vanilloid 1 (TRPV1) receptor activity by tesaglitazar which could provide a potential mechanism that underlie tesaglitazar antinociceptive effects.

Von Frey filaments were used to determine the paw withdrawal threshold (PWT) in adult male Sprague Dawley rats (180-250g) following i.p.

injection of streptozotocin (STZ) or cisplatin, which were used as models of neuropathic pain.

Antinociceptive effects of tesaglitazar were determined 6 hours after drug administration.

Cobalt influx assays in cultured dorsal root ganglia (DRG) neurons were used to study the effects of tesaglitazar preincubation on capsaicin-evoked cobalt influx.

Both cisplatin and STZ produced a significant decrease in PWT.

The higher dose of tesaglitazar (20μg/kg) significantly restored PWT in both neuropathic pain models (P<0.05).

10μM capsaicin produced a robust cobalt response in DRG neurons.

Preincubation of DRG neurones with tesaglitazar 6 hours prior to stimulation with capsaicin significantly reduce capsaicin-evoked cobalt responses in a PPARα and PPARγ dependent fashion (P<0.05).

In conclusion, tesaglitazar produced significant analgesic effects in STZ and cisplatin-induced neuropathy, possibly by modulating TRPV1 receptor activity.

This may be of potential benefit in clinical practice dealing with peripheral neuropathy.