Cannabinoid receptor type-2 modulates nociceptive signaling molecules in a model of post-concussion headache

The goal of this study was to investigate the role of the cannabinoid receptor type-2 (CB2R) in the trigeminal pain pathway in a model of post-concussion headache. Sprague Dawley rats were randomized to receive either a repeated mild closed head injury (CHI) or served as incision controls. Changes in CGRP, nNOS, and IBA-1 were assessed in the trigeminal nucleus caudalis (TNC) and trigeminal ganglia via IHC. A subset of CHI rats received either a cannabinoid receptor type 2 (CB2R) anti-inflammatory agonist (JWH133), an NSAID (Ketorolac), or vehicle and underwent von Frey testing for trigeminal allodynia. An in vitro brain slice study was performed on TNC and cerebrum slices incubated with capsaicin, capsaicin plus a or media control solutions for 24hrs; CGRP and PGE2 were assessed via ELISA. Repeated CHI showed increases in CGRP and PGE2, and altered nNOS and IBA-1 immunoreactivity in the trigeminal ganglia and TNC, respectively. JWH-133 blocked capsaicin-induced increases in CGRP and PGE2 in the TNC and cerebrum slices. Findings show the CB2R modulates trigeminal pain in a model of concussion, although the mechanisms eliciting analgesia warrant a more in depth investigation. Results Abstract