The opioid-mediated endogenous analgesia system can be activated by administering morphine or other opiate drugs. Opiates typically inhibit neural activity in nociceptive pathways. The inhibitory action of opiates occurs at two sites: presynaptic and postsynaptic. The presynaptic action of opiates on nociceptive afferent terminals prevents the release of excitatory transmitters such as substance P. The postsynaptic action of opiates produces an inhibitory postsynaptic potential. One hypothesis is that the descending analgesia system is under tonic inhibitory control by inhibitory interneurons in both the midbrain and medulla. Opiates inhibit these inhibitory interneurons, leading to disinhibition of the descending analgesia pathways. Nonopioid analgesia pathways can be engaged through certain forms of stress, resulting in stress-induced analgesia. Serotonin and catecholamines, such as norepinephrine and epinephrine, are neurotransmitters that can inhibit nociceptive neurons and play a role in the endogenous analgesia system. These monoamine neurotransmitters also interact with endogenous opioids. There is evidence for the existence of endogenous opiate antagonists that can prevent opiate analgesia.

1. Sensory neurons have their cell bodies in sensory nerve ganglia, such as dorsal root ganglia for body innervation and cranial nerve ganglia for face, oral and nasal cavities, and dura innervation. Proprioceptive neurons are found in the trigeminal mesencephalic nucleus. These sensory neurons connect peripherally to sensory receptors and centrally to second-order neurons in the spinal cord or brainstem.

2. The skin contains low-threshold mechanoreceptors, thermoreceptors, and nociceptors. Muscle, joints, and viscera have mechanoreceptors and nociceptors. Low-threshold mechanoreceptors can be rapidly or slowly adapting. Thermoreceptors include cold and warm receptors. Aδ and C nociceptors are responsible for detecting noxious mechanical, thermal, and chemical stimuli and may become sensitized by the release of chemical substances from damaged cells. The release of peptides and other substances from nociceptors themselves may contribute to inflammation.

3. Large primary afferent fibers enter the dorsal funiculus through the medial part of the dorsal root, while small primary afferent fibers enter the spinal cord through the lateral part of the dorsal root. Collaterals of these fibers synapse in the deep dorsal horn, intermediate zone, and ventral horn, contributing to sensory processing and motor control.
STT relay cell afferent Circulating opioid binding sites Opiate receptor Sub P. Enk Substance P receptor opioids include enkephalin, dynorphin, and β-endorphin. Opiate analgesia can generally be prevented or reversed by the narcotic antagonist naloxone. Therefore naloxone is frequently used to determine whether analgesia is mediated by an opioid mechanism.
The opioid-mediated endogenous analgesia system can be activated by exogenous administration of morphine or other opiate drugs. Thus one of the oldest medical treatments of pain depends on the triggering of a sensory control system. Opiates typically inhibit neural activity in nociceptive pathways. Two sites of action have been proposed for opiate inhibition, presynaptic and postsynaptic (see
Fig. 7.9D ). The presynaptic action of opiates on nociceptive afferent terminals is thought to prevent release of excitatory transmitters such as SP. The postsynaptic action of opiates produces an inhibitory postsynaptic potential. How can an inhibitory neurotransmitter activate descending pathways? One hypothesis is that the descending analgesia system is under tonic inhibitory control by inhibitory interneurons in both the midbrain and medulla. The action of opiates would inhibit the inhibitory inter-neurons and thereby disinhibit the descending analgesia pathways.
Some endogenous analgesia pathways operate by neurotransmitters other than opioids and thus are unaffected by naloxone. One way of engaging a nonopioid analgesia
CHAPTER 7 The Somatosensory System pathway is through certain forms of stress. The analgesia thus produced is a form of stress-induced analgesia.
Many neurons in the raphe nuclei use serotonin as a neurotransmitter. Serotonin can inhibit nociceptive neurons and presumably plays an important role in the endogenous analgesia system. Other brainstem neurons release catecholamines, such as norepinephrine and epinephrine, in the spinal cord. These catecholamines also inhibit nociceptive neurons; therefore catecholaminergic neurons may contribute to the endogenous analgesia system. Furthermore, these monoamine neurotransmitters interact with endogenous opioids. Undoubtedly, many other substances are involved in the analgesia system. In addition, there is evidence for the existence of endogenous opiate antagonists that can prevent opiate analgesia.
1.
Sensory neurons have cell bodies in sensory nerve ganglia: (1) dorsal root ganglia for neurons innervating the body and (2) cranial nerve ganglia for neurons innervating the face, oral and nasal cavities, and dura, except for proprioceptive neurons, which are in the trigeminal mesencephalic nucleus. They connect peripherally to a sensory receptor and centrally to second-order neurons in the spinal cord or brainstem.
2.
Skin contains low-threshold mechanoreceptors, thermoreceptors, and nociceptors. Muscle, joints, and viscera have mechanoreceptors and nociceptors. Low-threshold mechanoreceptors may be rapidly or slowly adapting. Thermoreceptors include cold and warm receptors. Aδ and C nociceptors detect noxious mechanical, thermal, and chemical stimuli and may be sensitized by release of chemical substances from damaged cells. Peripheral release of substances, such as peptides, from nociceptors themselves may contribute to inflammation.
3.
Large primary afferent fibers enter the dorsal funiculus through the medial part of the dorsal root; collaterals synapse in the deep dorsal horn, intermediate zone, and ventral horn. Small primary afferent fibers enter the spinal cord through the lateral part of the dorsal root; collaterals synapse in the dorsal horn.
4.