Comparing the Induction of Medication Overuse Headache in Male and Female Rats and Resultant Temporal Regulation of the Pag Proteome

Abstract

Headache subtypes can be grouped by underlying etiologies, frequency, mechanisms implicated, and symptomology. Etiologically, three classifications of headache include vascular, tension-type, and traction and inflammatory headache. There are also primary and secondary headaches. Secondary headaches are caused by local or systemic illness [2]. Medication overuse headache (MOH) is a secondary headache that is caused by chronic use of acute headache medication, including as prescribed/recommended and misused. The most frequent overused drugs implicated in MOH are triptans, opioids and barbiturates.[5] Male and female rat MOH models were used to determine magnitude, onset and frequency of MOH. Across each day post infusion, all days there are more male than female rats that showed allodynia. It is also consistent across treatments in females that at day 10 there are fewer rats who show periorbital mechanical allodynia compared to day 4 and day 7. It is consistent in both male and female that sumatriptan has more animals with periorbital mechanical allodynia this suggest that sumatriptan and morphine do not have the same susceptibility potential for MOH. Although this needs to be further investigated since the n value for morphine animals are below significant value. Western blots were then performed to measure changes in CB1R and DAGLα. When it came to DAGLα. there was no significant difference between the naive and the saline treated rats. There were also no differences found between sex. For CB1R there was no significant difference found between naive and saline as a whole or when the treatments were separated by sex. When it came to DAGLα. and CB1R there was no significant difference between treatments during day 4 of treatment. There were no significant changes between saline, sumatriptan or morphine for day 10 of treatment. Next total and phosphor-proteomics were done to look for widespread changes in both the ECS as well as overall PAG function. Within the total proteomic of naive vs saline comparisons DAVID found genomic pathways related to addiction and dopaminergic systems. For total proteome of day 7 comparison DAVID found genomes related to addiction, dopaminergic system, and glutamate. For total proteomic of morphine comparison DAVID found genomes related to glutamate, and addiction. For total proteomic of sumatriptan comparison DAVID found genomes related to glutamate, ECB and estrogen signaling. For total proteomic of day 4 comparison DAVID found genomes related to estrogen signaling. For total proteomic day 10 comparison DAVID found genome related to neurogenerative diseases. For phospho- proteomic naive vs saline comparison, DAVID found genomes related to neurodegenerative diseases. For phospho-proteomic comparison across saline DAVID found genomes related to neurodegenerative diseases and estrogen signaling. For phospho-proteomic day 7 comparison neurodegenerative diseases and estrogen signaling was found. For phospho-proteomic day 4 comparison DAVID found neurodegenerative diseases and addiction. For phospho-proteomic comparison across day 10 DAVID found neurodegenerative diseases and dopaminergic system. For phospho-proteomic comparison across morphine DAVID found neurodegenerative diseases and addiction. For phospho-proteomic the comparison of sumatriptan DAVID found neurodegenerative diseases.