Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain
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-...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2019/2630232 |
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| author | Mohammad Alsalem Mansour Haddad Sara A. Aldossary Heba Kalbouneh Belal Azab Aala Dweik Amer Imraish Khalid El-Salem |
| author_facet | Mohammad Alsalem Mansour Haddad Sara A. Aldossary Heba Kalbouneh Belal Azab Aala Dweik Amer Imraish Khalid El-Salem |
| author_sort | Mohammad Alsalem |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-426b5791609444c594eed89c1dbe6978 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-426b5791609444c594eed89c1dbe69782025-02-03T05:43:57ZengWileyPPAR Research1687-47571687-47652019-01-01201910.1155/2019/26302322630232Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic PainMohammad Alsalem0Mansour Haddad1Sara A. Aldossary2Heba Kalbouneh3Belal Azab4Aala Dweik5Amer Imraish6Khalid El-Salem7Faculty of Medicine, The University of Jordan, Amman 11942, JordanFaculty of Pharmacy, Philadelphia University, Amman 19392, JordanFaculty of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaFaculty of Medicine, The University of Jordan, Amman 11942, JordanFaculty of Medicine, The University of Jordan, Amman 11942, JordanFaculty of Medicine, The University of Jordan, Amman 11942, JordanFaculty of Science, The University of Jordan, Amman 11942, JordanFaculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanNeuropathic 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.http://dx.doi.org/10.1155/2019/2630232 |
| spellingShingle | Mohammad Alsalem Mansour Haddad Sara A. Aldossary Heba Kalbouneh Belal Azab Aala Dweik Amer Imraish Khalid El-Salem Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain PPAR Research |
| title | Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain |
| title_full | Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain |
| title_fullStr | Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain |
| title_full_unstemmed | Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain |
| title_short | Effects of Dual Peroxisome Proliferator-Activated Receptors α and γ Activation in Two Rat Models of Neuropathic Pain |
| title_sort | effects of dual peroxisome proliferator activated receptors α and γ activation in two rat models of neuropathic pain |
| url | http://dx.doi.org/10.1155/2019/2630232 |
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