The endogenous opioid system comprises three originally described opioid receptors, MOR, KOR, and DOR and endogenous opioid peptide-expressing genes proopiomelanocortin (POMC), prodynorphin (PDYN), and proenkephalin (PENK) (Brownstein 1993; Trescot et al. 2008; Bodnar 2010; Pasternak and Pan 2013), as well as a fourth receptor (OPRN1) and peptide (nociceptin/orphanin FQ) family member. The endogenous opioid system has a fundamental role in pain regulation and has been implicated in the pathophysiology of various neurologic diseases (Nandhu et al. 2010; Sauriyal et al. 2011; Benarroch 2012) and in pain management (Bruehl et al. 2013).