Endogenous analgesic system

The endogenous analgesic system is a built-in neuronal system that suppresses transmission of nervous impulses in the pain pathway. It functions by way of the following neurotransmitters produced in the CNS  

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. 

The endogenous analgesic pathway has three major components  

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

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Explain how the endogenous analgesic system suppresses pain... 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

There are two main hypotheses about the involvement of endogenous opioid systems in the maintenance of self-injurious behaviors (Sandman, 1988 Buitelaar, 1993). The pain hypothesis suggests that in some subjects self-injury does not induce pain because excessive basal activity of opioid systems in the CNS has led to an opioid analgesic state. The addiction hypothesis posits that particularly repetitive and stereotyped forms of self-injury stimulate the production and release of en-dogeneous opioids. Therefore, chronic maintenance of self-injury may be due to addiction to endogenous opioids or to positive reinforcement by a central release of opioids triggered by the self-injurious behavior. Irrespective of which hypothesis one favors, treatment with opiate antagonists seems to be a rational approach. 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

Opioid analgesics stimulate the release of ADH, prolactin, and somatotropin but inhibit the release of luteinizing hormone. These effects suggest that endogenous opioid peptides, through effects in the hypothalamus, regulate these systems (Table 31-1). 

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