Role of the Endocannabinoid Selective COX-2 Inhibition in Post-Traumatic Headache Associated with Repetitive Mild Traumatic Brain Injury
Abstract
Posttraumatic headache (PTH) is one of the most common and debilitating symptoms following traumatic brain injury (TBI), and it can resemble the migraine-like phenotype. Although augmentation of the endogenous cannabinoids has been shown to have protective effects in animal models of TBI and migraine, it is unknown whether targeting the endocannabinoid system is also effective in PTH. Using a recently developed closed-head impact model of engineered rotational acceleration (CHIMERA), we found that treatment with the inhibitor of 2-AG hydrolytic enzyme MAGL, MJN110 for 7 days significantly reduced periorbital allodynia and blocked the late development of pain sensitivity to low dose of CGRP in TBI animals. Accumulation of microglia and astrocytes and the production of CGRP in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were significantly reduced by MJN110 treatment. Mass spectrometry revealed the reduced production of 2-AG in TG and TNC following the last TBI impact, suggesting a causal role to the development of PTH. This study suggested that augmentation of the endogenous 2-AG by inhibition of its hydrolysis is likely to be a therapeutic strategy for PTH attributed to repetitive mTBI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190863
Entities
People
- Yumin Zhang
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine