Enkephalin is a naturally occurring substance produced in the central nervous system and other tissues. It belongs to a class of molecules known as peptides, which are short chains of amino acids that function as neurotransmitters. These peptides carry signals between nerve cells. Their primary function relates to the body’s system for managing pain, though their influence extends to emotional states and stress responses.
The Body’s Natural Opioids
Enkephalins are a family within the body’s internally produced opioid system and are distinct from the more widely known endorphins. The key difference lies in their origin and structure. Enkephalins are derived from a precursor protein called proenkephalin, whereas endorphins are synthesized from a different precursor. While both interact with opioid receptors, they have different primary targets and functional roles.
There are two primary forms: Met-enkephalin and Leu-enkephalin, named for the amino acid at their end—methionine or leucine. Both are pentapeptides, meaning they consist of a five-amino-acid chain, and are created when the larger proenkephalin protein is cleaved by enzymes. A single proenkephalin molecule can be processed to yield four copies of Met-enkephalin and one copy of Leu-enkephalin.
These molecules are distributed throughout the brain, spinal cord, and adrenal glands. The discovery of enkephalins in 1975 was a turning point, revealing that the body produces its own substances that act on the same receptors as opioid drugs like morphine. This finding opened up a new field of research into the body’s pain-control mechanisms.
How Enkephalins Work
Enkephalins exert their effects by acting as signaling molecules that bind to specific sites on nerve cells called opioid receptors. Enkephalins show a high affinity for the delta-opioid receptor and, to a lesser extent, the mu-opioid receptor. This interaction is often compared to a key fitting into a lock, with the enkephalin molecule as the key and the receptor as the lock.
When an enkephalin molecule binds to its receptor, it initiates a cascade of changes inside the neuron. This process leads to an inhibitory effect on the neuron, making it less likely to fire and transmit a signal. This is the basis of enkephalin’s pain-modulating ability.
In pain pathways, nerve endings release neurotransmitters like Substance P to carry pain signals to the brain. When enkephalins bind to receptors on these nerve endings, they block the release of Substance P. This action dampens the pain message before it can be fully perceived by the brain, providing natural analgesia.
Key Roles in the Body
The primary role of enkephalins is pain modulation. By inhibiting the transmission of pain signals in the brain and spinal cord, they act as the body’s own painkillers. This system is active in areas of the brainstem and spinal cord that are dense with opioid receptors, allowing for control over pain-sensing information.
Beyond pain relief, enkephalins help regulate mood and emotional responses. High concentrations of these peptides and their receptors are found in the brain’s limbic system, which governs emotions. Their activity in these regions can influence feelings of well-being and modulate the body’s response to stress, suggesting a role in stress resilience.
Enkephalins also contribute to the brain’s reward system, as a key reward circuit is rich in opioid receptors. When enkephalins activate these receptors, they can promote the release of dopamine, a neurotransmitter associated with pleasure and reinforcement. This mechanism is part of how the brain processes rewarding experiences.
Medical and Therapeutic Context
Despite their pain-relieving properties, enkephalins are not viable as therapeutic drugs. Their limitation is an extremely short half-life, as they are rapidly broken down by enzymes. This rapid degradation means their effects would be too fleeting to provide clinical benefit if administered as a drug.
This has led researchers to focus on protecting the body’s own enkephalins using drugs known as enkephalinase inhibitors. These medications work by blocking the enzymes that degrade enkephalins. By inhibiting these enzymes, the drugs allow naturally released enkephalins to remain active for longer, enhancing their effects.
Enkephalinase inhibitors, such as racecadotril, represent a promising therapeutic approach. They amplify the body’s pain-control system rather than introducing an external opioid. This may offer a way to manage pain with a lower risk of side effects associated with traditional opioid medications, making it an active area of research.