*2.1. Animals*

Sprague–Dawley male rats (200–230 g, Envigo, Milan, Italy) were used throughout. They received food and *water ad libitum*. The University of Messina Review Board for animal care approved the study. All in vivo experiments followed the new regulations of USA (Animal Welfare Assurance No A5594-01), Europe (EU Directive 2010/63), Italy (D.Lgs 2014/26), and the ARRIVE guidelines.

## *2.2. Induction of Experimental Fibromyalgia*

Reserpine administration was performed by subcutaneous injection of 1 mg/kg for three consecutive days [38]. Reserpine (Sigma-Aldrich, Saint Louis, MO, USA) was dissolved in distilled water with 0.5% acetic acid (vehicle). Animals from the sham group received the same volume of vehicle, but they were administered no reserpine.
