Dynorphin A
Pain / Mood / StressAlso known as: Dynorphin A, Dynorphin A(1-17), Dyn A, Big Dynorphin
Mechanism
Dynorphin A is the body's primary kappa-opioid receptor activator. Unlike the euphoria-producing mu-opioid system (beta-endorphin), kappa activation by dynorphin produces dysphoria and aversion — it is the "anti-reward" signal. The brain releases dynorphin during stress and drug withdrawal to create negative emotional states. Understanding dynorphin has been key to addiction research and the development of kappa antagonists for depression.
Technical detail
Dynorphin A (1-17) is a 17-amino-acid peptide derived from prodynorphin (PDYN) processing. It is the most potent endogenous kappa-opioid receptor (KOR) agonist. KOR activation in the nucleus accumbens and VTA couples through Gi/Go to inhibit dopamine release, producing dysphoria and aversion (opponent process to mu-opioid reward). Signaling involves beta-arrestin 2 recruitment, p38 MAPK activation, and CREB phosphorylation. Dynorphin is upregulated by chronic stress and substance abuse, contributing to negative reinforcement and anhedonia. Also modulates pain at spinal and supraspinal levels with complex pro- and anti-nociceptive effects depending on context.