Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors
Objective(s): Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generati...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2017-11-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | http://ijbms.mums.ac.ir/article_9500_84b9ae720847dd5ca90680245a5e6eee.pdf |
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| author | Alireza Abed Mohammad Javad Khoshnoud Mehdi Taghian Mahbubeh Aliasgharzadeh Azam Mesdaghinia |
| author_facet | Alireza Abed Mohammad Javad Khoshnoud Mehdi Taghian Mahbubeh Aliasgharzadeh Azam Mesdaghinia |
| author_sort | Alireza Abed |
| collection | DOAJ |
| description | Objective(s): Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine. |
| first_indexed | 2024-12-11T05:04:40Z |
| format | Article |
| id | doaj.art-3f020e15923f49aabdec145fae5365b3 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-11T05:04:40Z |
| publishDate | 2017-11-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-3f020e15923f49aabdec145fae5365b32022-12-22T01:20:03ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742017-11-0120111182118810.22038/ijbms.2017.95009500Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptorsAlireza Abed0Mohammad Javad Khoshnoud1Mehdi Taghian2Mahbubeh Aliasgharzadeh3Azam Mesdaghinia4Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, IranDepartment of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Oral and Maxillofacial Surgery, School of Dentistry, Mazandaran University of Medical Science, Sari, IranSchool of Pharmacy, International Branch, Shiraz University of Medical Sciences, Shiraz, IranPhysiology Research Center, Kashan University of Medical Sciences, Kashan, Iran|Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, IranObjective(s): Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.http://ijbms.mums.ac.ir/article_9500_84b9ae720847dd5ca90680245a5e6eee.pdfHyperalgesiaMiceNeuropathic painPaclitaxelQuetiapineYohimbine |
| spellingShingle | Alireza Abed Mohammad Javad Khoshnoud Mehdi Taghian Mahbubeh Aliasgharzadeh Azam Mesdaghinia Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors Iranian Journal of Basic Medical Sciences Hyperalgesia Mice Neuropathic pain Paclitaxel Quetiapine Yohimbine |
| title | Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors |
| title_full | Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors |
| title_fullStr | Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors |
| title_full_unstemmed | Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors |
| title_short | Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors |
| title_sort | quetiapine reverse paclitaxel induced neuropathic pain in mice role of alpha2 adrenergic receptors |
| topic | Hyperalgesia Mice Neuropathic pain Paclitaxel Quetiapine Yohimbine |
| url | http://ijbms.mums.ac.ir/article_9500_84b9ae720847dd5ca90680245a5e6eee.pdf |
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