In addition, whether other hypothalamic neuropeptides with known effects in both feeding control and the modulation of nociceptive processing, such as orexin, oxytocin (OT), neuropeptide Y (NPY), and pituitary adenylate cyclase activating protein (PACAP) (53), are also important players in the association between obesity and headache remains to be elucidated. Here, HCRT is linked to obesity due to melanocortin 4 receptor deficiency.