Leu-Enkephalin is an endogenous neuropeptide involved in nociception and an agonist of δ- and µ-opioid receptors (Kis = 4.0 and 3.4 nM, respectively).It is selective for δ- and µ- over κ-opioid receptors (Ki = >1,000 nM). Leu-Enkephalin is a cleavage product of proenkephalin, which is found primarily in the adrenal medulla and the CNS. It is found in the brain, the brainstem, and the spinal cord as well as in the peripheral nervous system. Leu-Enkephalin (1 mg/kg) decreases the visceromotor response to colon distension in a mouse model of visceral pain induced by colorectal distension.It also increases the tail-flick threshold and latency to tail flick in the tail-pressure test and tail-flick test, respectively, in mice.