?-adrenoceptor blockade prevents the attenuation of endogenous analgesia during persistent pain

During chronic pain syndromes, inhibitory endogenous pain modulation circuits, such as the Ascending Nociceptive Control (ANC), are impaired (Miranda et al., 2015). The ANC is activated by a nociceptive stimulus (e.g., a capsaicin injection) and triggers a hetero-segmental antinociception that lasts more than one hour (Tambeli et al., 2009). Persistent pain is associated with ANC activity reduction, and this effect seems sympathoadrenal dependent (Ferrari et al., 2010). The adrenal medulla produces and releases epinephrine, which acts mainly on ?- adrenergic receptors. However, whether the activation of these receptors decreases the analgesia duration of the ANC during persistent hyperalgesia is unknown. Therefore, we hypothesized that the blockade of ?-adrenergic receptors prevents the decreased analgesia duration of the ANC induced by persistent hyperalgesia.