Endorphins are found primarily in the limbic system, hypothalamus, and brainstem. Enkephalins and dynorphin (in smaller quantities) are found primarily in the periaqueductal gray matter (PAG) of the midbrain, the limbic system, and the hypothalamus. These endogenous substances mimic the effects of morphine and other opiate drugs at many points in the analgesic system, including in the dorsal horns of the spinal cord.

Opioid receptors are highly concentrated in the PAG area of the mid-brain. Stimulation of this region produces long-lasting analgesia with no effect on the level of consciousness. For these reasons, the PAG area is often referred to as the endogenous analgesia center. This area receives input from many regions of the CNS, including the cerebral cortex; hypothalamus; reticular formation of the brainstem; and spinal cord by way of the spinotha-lamic tracts. This region is also interconnected with the limbic system, which is responsible for the emotional response to pain.

The endogenous analgesic pathway has three major components:

• Periaqueductal gray area

• Nucleus raphe magnus

• Pain inhibitory complex in the dorsal horns of the spinal cord

The endogenous analgesic pathway begins in the PAG area, in which neurons descend to the nucleus raphe magnus (NRM) in the medulla (see Figure 8.2). Neurons of the NRM then descend to the dorsal horn of the spinal cord where they synapse with local spinal interneurons. The inter-neurons then synapse with incoming pain fibers. Many of the neurons derived from the PAG area secrete enkephalin from their axon terminals in the NRM. The neurons derived from the NRM secrete serotonin from their axon terminals in the spinal cord. The serotonin stimulates the local cord interneurons to secrete enkephalin. The enkephalin then causes presynaptic inhibition of the incoming pain fibers. Binding of enkephalin to opioid receptors on these pain fibers blocks calcium channels in the axon terminals. Because the influx of calcium is necessary for the exocytosis of neurotrans-mitter, blocking these channels prevents release of substance P. As a result, this system interrupts the pain signal at the level of the spinal cord.

The endogenous analgesic system is normally inactive. It remains unclear how this system becomes activated. Potential activating factors include exercise, stress, acupuncture, and hypnosis.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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