Opioid receptors are widely distributed in brain, spinal cord and peripheral sensory and autonomic nerves. They are activated physiologically by the products of endogenous opioid peptide genes such as proenkephalin, podynorphin, pro-opiomelancortin and pronociceptin. Four opioid receptor subtypes have been identified including µ, δ, κ, and ORL1. All of these subtypes are coupled to cAMP modulation via Gi/o but each subtype has a distinct pharmacological profile.