Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats
Paclitaxel (PTX) is a commonly used chemotherapeutic drug, however, one of its major adverse effects is chronic neuropathic pain, with the incidence being higher in women than in men. The neurobiological mechanisms behind this sex difference are still largely unclear, and the endocannabinoid system,...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1505980/full |
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| author | Chiara Di Marino Chiara Di Marino Chiara Di Marino Chiara Di Marino Álvaro Llorente-Berzal Álvaro Llorente-Berzal Álvaro Llorente-Berzal Alba M. Diego Alba M. Diego Alba M. Diego Ariadni Bella Ariadni Bella Ariadni Bella Laura Boullon Laura Boullon Laura Boullon Esther Berrocoso Esther Berrocoso Esther Berrocoso Michelle Roche Michelle Roche Michelle Roche David P. Finn David P. Finn David P. Finn |
| author_facet | Chiara Di Marino Chiara Di Marino Chiara Di Marino Chiara Di Marino Álvaro Llorente-Berzal Álvaro Llorente-Berzal Álvaro Llorente-Berzal Alba M. Diego Alba M. Diego Alba M. Diego Ariadni Bella Ariadni Bella Ariadni Bella Laura Boullon Laura Boullon Laura Boullon Esther Berrocoso Esther Berrocoso Esther Berrocoso Michelle Roche Michelle Roche Michelle Roche David P. Finn David P. Finn David P. Finn |
| author_sort | Chiara Di Marino |
| collection | DOAJ |
| description | Paclitaxel (PTX) is a commonly used chemotherapeutic drug, however, one of its major adverse effects is chronic neuropathic pain, with the incidence being higher in women than in men. The neurobiological mechanisms behind this sex difference are still largely unclear, and the endocannabinoid system, which exhibits sexual dimorphism and plays a key role in pain regulation, is a promising area for further studies. The present study aimed to characterise pain-, cognition-, anxiety-, and depression-related behaviours in male and female rats following PTX administration, and associated alterations in the endocannabinoid system. After the induction of the model, pain-related behaviours were assessed using von Frey, Acetone Drop and Hargreaves’ tests, Novel Object Recognition and T-Maze Spontaneous Alternation tests were used for cognition-related behaviours, Elevated Plus Maze, Open Field, and Light Dark Box tests were used to assess anxiety-related behaviours, and Sucrose Preference, Sucrose Splash, and Forced Swim tests for depression-related behaviours. At each time point analysed, animals treated with PTX exhibited mechanical and cold hypersensitivity, with females displaying lower hind paw withdrawal thresholds to mechanical stimulation than males. No PTX-induced alterations in the other behavioural tests were detected. Post-mortem measurement of endocannabinoid and related N-acylethanolamine levels in spinal cord and discrete brain regions revealed a PTX-induced increase of 2-Arachidonoyl Glycerol (2-AG), N-Palmitoylethanolamine (PEA) and N-Oleoylethanolamine (OEA) levels in the amygdala of male and female animals, but not in the other areas. Collectively, these results suggest that PTX causes similar long-lasting hypersensitivity to mechanical and cold stimuli, but not heat, in rats of both sexes, effects accompanied by increases in amygdalar levels of endocannabinoids and N-acylethanolamines. |
| format | Article |
| id | doaj-art-933940ca43df4b4090a0cdaa145befa4 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-933940ca43df4b4090a0cdaa145befa42025-01-03T06:46:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15059801505980Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female ratsChiara Di Marino0Chiara Di Marino1Chiara Di Marino2Chiara Di Marino3Álvaro Llorente-Berzal4Álvaro Llorente-Berzal5Álvaro Llorente-Berzal6Alba M. Diego7Alba M. Diego8Alba M. Diego9Ariadni Bella10Ariadni Bella11Ariadni Bella12Laura Boullon13Laura Boullon14Laura Boullon15Esther Berrocoso16Esther Berrocoso17Esther Berrocoso18Michelle Roche19Michelle Roche20Michelle Roche21David P. Finn22David P. Finn23David P. Finn24Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandDepartment of Neuroscience, Neuropsychopharmacology and Psychobiology Research Group, University of Cádiz, Cádiz, SpainPharmacology and Therapeutics, School of Medicine, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandPharmacology and Therapeutics, School of Medicine, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandPhysiology, School of Medicine, University of Galway, Galway, IrelandPharmacology and Therapeutics, School of Medicine, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandDepartment of Neuroscience, Neuropsychopharmacology and Psychobiology Research Group, University of Cádiz, Cádiz, SpainInstituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Cádiz, SpainCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, SpainGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandPhysiology, School of Medicine, University of Galway, Galway, IrelandPharmacology and Therapeutics, School of Medicine, University of Galway, Galway, IrelandGalway Neuroscience Centre, University of Galway, Galway, IrelandCentre for Pain Research, University of Galway, Galway, IrelandPaclitaxel (PTX) is a commonly used chemotherapeutic drug, however, one of its major adverse effects is chronic neuropathic pain, with the incidence being higher in women than in men. The neurobiological mechanisms behind this sex difference are still largely unclear, and the endocannabinoid system, which exhibits sexual dimorphism and plays a key role in pain regulation, is a promising area for further studies. The present study aimed to characterise pain-, cognition-, anxiety-, and depression-related behaviours in male and female rats following PTX administration, and associated alterations in the endocannabinoid system. After the induction of the model, pain-related behaviours were assessed using von Frey, Acetone Drop and Hargreaves’ tests, Novel Object Recognition and T-Maze Spontaneous Alternation tests were used for cognition-related behaviours, Elevated Plus Maze, Open Field, and Light Dark Box tests were used to assess anxiety-related behaviours, and Sucrose Preference, Sucrose Splash, and Forced Swim tests for depression-related behaviours. At each time point analysed, animals treated with PTX exhibited mechanical and cold hypersensitivity, with females displaying lower hind paw withdrawal thresholds to mechanical stimulation than males. No PTX-induced alterations in the other behavioural tests were detected. Post-mortem measurement of endocannabinoid and related N-acylethanolamine levels in spinal cord and discrete brain regions revealed a PTX-induced increase of 2-Arachidonoyl Glycerol (2-AG), N-Palmitoylethanolamine (PEA) and N-Oleoylethanolamine (OEA) levels in the amygdala of male and female animals, but not in the other areas. Collectively, these results suggest that PTX causes similar long-lasting hypersensitivity to mechanical and cold stimuli, but not heat, in rats of both sexes, effects accompanied by increases in amygdalar levels of endocannabinoids and N-acylethanolamines.https://www.frontiersin.org/articles/10.3389/fphar.2024.1505980/fullpaclitaxelchemotherapyneuropathic painendocannabinoidsbehaviour |
| spellingShingle | Chiara Di Marino Chiara Di Marino Chiara Di Marino Chiara Di Marino Álvaro Llorente-Berzal Álvaro Llorente-Berzal Álvaro Llorente-Berzal Alba M. Diego Alba M. Diego Alba M. Diego Ariadni Bella Ariadni Bella Ariadni Bella Laura Boullon Laura Boullon Laura Boullon Esther Berrocoso Esther Berrocoso Esther Berrocoso Michelle Roche Michelle Roche Michelle Roche David P. Finn David P. Finn David P. Finn Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats Frontiers in Pharmacology paclitaxel chemotherapy neuropathic pain endocannabinoids behaviour |
| title | Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats |
| title_full | Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats |
| title_fullStr | Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats |
| title_full_unstemmed | Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats |
| title_short | Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats |
| title_sort | characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain related behaviour anxiodepressive behaviour cognition and the endocannabinoid system in male and female rats |
| topic | paclitaxel chemotherapy neuropathic pain endocannabinoids behaviour |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1505980/full |
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