The impact of morphine on nerve injury recovery and lipid metabolism pathways

Stokes-Heck, Sierra

The impact of morphine on nerve injury recovery and lipid metabolism pathways

dc.contributor.advisor	Trang, Tuan
dc.contributor.author	Stokes-Heck, Sierra
dc.contributor.committeemember	Ousman, Shalina
dc.contributor.committeemember	Stys, Peter
dc.date	2023-06
dc.date.accessioned	2023-03-31T14:53:27Z
dc.date.available	2023-03-31T14:53:27Z
dc.date.issued	2023-03-30
dc.description.abstract	Neuropathic pain resulting from peripheral nerve injury is among the most debilitating types of chronic pain conditions. Opioid medications are often used despite their poor efficacy in treating neuropathic pain symptoms and concerns about adverse effects. Notably, emerging evidence suggests that rather than alleviating neuropathic pain, opioids may worsen mechanical allodynia, wherein innocuous stimuli elicit pain. Morphine has been shown to exacerbate nerve injury-induced mechanical allodynia, but the cause is not understood. Both morphine and nerve injury have been implicated in myelin and oligodendrocyte perturbations. As myelin is primarily composed of lipids, here I determined whether spinal lipid metabolism alterations are a potential mechanism underlying morphine exacerbated neuropathic pain. In this study, I characterized neuropathic pain development and recovery using the chronic constriction injury model (CCI), which results in robust mechanical allodynia. I demonstrated that delayed morphine treatment of CCI animals resulted in prolonged mechanical allodynia and recovery from nerve injury, as compared to nerve injured mice given saline. Using profiling arrays for cholesterol metabolism and lipoprotein signaling, I found that morphine further increases the CCI-induced lipid metabolism changes within the spinal cord. More specifically, I found that cholesterol metabolic and lipoprotein clearance pathways are upregulated in nerve injured animals given saline when earlier and later timepoints are compared, suggesting their role in recovery. Conversely, these same pathways are downregulated in morphine treated CCI animals. To confirm these results, I validated the six most dysregulated gene candidates and found that Cyp11a1 was significantly upregulated in CCI animals treated with morphine. These results suggest that morphine could be delaying recovery from CCI by dysregulating lipid metabolism at the spinal cord level. As glial cells are involved in lipid synthesis and maintenance of myelin, alterations in lipid metabolism could be linked to changes in oligodendrocytes, astrocytes, microglia, and myelination. These findings could help mitigate adverse opioid effects and improve treatment for people suffering from neuropathic pain.
dc.identifier.citation	Stokes-Heck, S. (2023). The impact of morphine on nerve injury recovery and lipid metabolism pathways (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://prism.ucalgary.ca/handle/1880/115966
dc.identifier.uri	https://dx.doi.org/10.11575/PRISM/dspace/40812
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject.classification	Neuroscience
dc.title	The impact of morphine on nerve injury recovery and lipid metabolism pathways
dc.type	master thesis
thesis.degree.discipline	Medicine – Neuroscience
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.