This dataset comprises the findings obtained in the study aimed at investigating the effects of URB937, a peripherally restricted fatty-acid amide hydrolase (FAAH) inhibitor, in two rat models that capture aspects of acute and chronic migraine, and are based on single or repeated administration of the vasodilating drug, nitroglycerin (NTG). The orofacial nocifensive behavior and mRNA levels of neuropeptides and pro-inflammatory cytokines along with tissue levels of anandamide and palmitoylethanolamide (PEA) were measured in trigeminal ganglia and medulla. All evaluations were made in rats that received a single injection of URB937 (1 mg/kg i.p.) either before or after NTG administration (10 mg/kg, i.p.) within the acute model, or daily URB937 (1 mg/kg i.p.) injections within the NTG (5 mg/kg, i.p.) chronic model. In the acute migraine model, we also investigated the effect of subtype-selective antagonist for cannabinoid receptors 1 and 2 (AM251 and AM630, respectively). Specifically, we achieved the following evaluations: 1. Measurement of AEA and PEA levels: medulla and trigeminal ganglia were homogenized in cold methanol (2 ml) containing AEA-d4 and PEA-d4 as internal standards. After extraction the lipids were measured using a Xevo TQ UPLC-MS/MS system equipped with a reversed-phase BEH C18 column (2.1 × 50 mm, 1.7 μm particle size) (Waters, Milford, USA). 2. Pain-related behavior in the orofacial formalin test: the face rubbing was measured counting the seconds the animal spent grooming the injected area (upper lip, lateral to the nose) with the ipsilateral forepaw or hindpaw 0–6 min (Phase I) or 12–45 min (Phase II) after formalin injection (50 µl, s.c.). The observation time was divided into 15 blocks of 3 min each. 3. mRNA expression levels: calcitonin gene-related peptide (CGRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) mRNA were evaluated in in medulla and trigeminal ganglia. mRNA levels were measured by rt-PCR. All samples were assayed in triplicate and gene expression levels were calculated according to 2−∆∆Ct = 2− (∆Ct gene − ∆Ct housekeeping gene) formula by using Ct (cycle threshold) values.

Funding; Ricerca Finalizzata 2013, Ministry of Health (Italy)