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

Authors
M Alsalem, M Haddad, SA Aldossary, H Kalbouneh et al


Lab
Faculty of Medicine, The University of Jordan, Amman 11942, Jordan

Journal
PPAR Research

Abstract
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 alpha and gamma (PPARalpha and gamma) 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 (20microg/kg) significantly restored PWT in both neuropathic pain models (P<0.05). 10_M 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 PPAR_ and PPAR_ 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.

BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)

Related products

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.