Question

Enkephalins are morphine like substances produced in the body. Enkephalins presynaptically inhibit the release of neurotransmitter from neurons that convey signals from nociceptors in the skin to the spinal cord. Based on your knowledge of the functional anatomy of a synapse and presynaptic modulation at axoaxonic synapses, explain how enkephalins, and morphine, decrease perception of pain, which occurs at the level of the brain.

Answer 1

Ans :

Enkephalins are small peptides that can serve as neurotransmitters in the brain. Enkephalins act to attenuate substance P release in the dorsal horn of the spinal cord and inhibit afferent pain fibers. Opiates inhibit transmission at sympathetic and locus caeruleus synapses.

Mechanism of action -

Enkephalin is also considered a neuropeptide, which in the human body performs as an important signaling molecule in the brain. Enkephalins are found in high concentration in the brain as well as in the cells of adrenal medulla. In response to pain, norepinephrine, a hormone that is activated in fight-or-flight response is released along with endorphins. It has been shown that this polypeptide is linked to brain functioning during a stressful response, especially in the hippocampus and prefrontal cortex regions. During a stress response, several Met-enkephalin analogs had increased activity in the hippocampus, while Leu-enkephalin analogs as well as somatostatins were downregulated during stress. This observation leads to a conclusion that stressors impact neuropeptides, and that their action is localized to a specific brain region.

Pain perception :

Enkephalins, pentapeptides containing the consensus Tyr-Gly-Gly-Phe-Xaa sequence, are the smallest of the molecules with pain killing or opiate activity. Enkephalins are found in the thalamus of the brain and in some parts of the spinal cord that transmit pain impulses. In the spinal cord, enkephalins inhibit painful sensations by reacting with specific receptor sites on the sensory nerve endings. Nerve endings of the central nervous system (CNS) and the adrenal medulla release these naturally occurring morphine-like substances. Enkephalins bind to opiate receptors and release controlled levels of pain. Leu-enkephalin is an endogenous agonist for the receptors that are stimulated by opiate alkaloids. It has multiple effects on the CNS, including the neuroendocrine hypothalamus. Leu-enkephalin also controls gonadal function. Met-enkephalin is involved in phenomena associated with modulated pain perception, regulation of memory and emotional conditions, food and liquid consumption and regulation of immunological system. It also has an impact on the digestive system motility, gastric as well as in pancreatic secretion and metabolism of carbohydrates