Investigating the Endocannabinoid System to Create a New Chronic Pain Treatment

While feeling pain is normal and essential to survival, some people are burdened with chronic pain. Chronic pain is defined as pain that persists for more than three months, and it is estimated that 52% of patients treated in primary care settings have a chronic pain diagnosis (Barrett and Chang, 2016). Current treatments for chronic pain, such as nonsteroidal anti-inflammatory drugs and opioids, are often ineffective and/or unreliable for patients. One potential treatment approach may be endocannabinoid-based therapies. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), are lipid-based neurotransmitters found throughout the animal kingdom. Previous pharmacological studies by our lab have found that 2-AG depresses nociceptive, or pain, synapses in the medicinal leech (Hirudo erbena). 2-AG is synthesized by the transmembrane protein diacylglycerol lipase (DAGL). The goal of my research is to understand the conserved biochemical and molecular properties of the Hirudo DAGL protein (hirDAGL). Our hypothesis is that a mutation in the catalytic region of the hirDAGL gene will knock out the protein’s function to synthesize 2-AG, but will not affect the protein’s localization to the plasma membrane. This research will lead to a further understanding of the role of hirDAGL in the production of 2-AG, which could lead to a better understanding of the endocannabinoid system in humans and the development of new chronic pain treatments