Peripheral nervous system concepts

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

The gap across the synapse is so small that the chemical messenger (neurotransmitter) crosses the cleft in less than a millisecond. Within the brain there are more than 50 neurotransmitters, which include amino acids, amines, purines, peptides and some gases. In contrast, in the peripheral nervous system there are only two, acetylcholine and noradrenaline. One of several questions concerning the concept of neurotransmitters is whether they differ, in principle, from local hormones (See below and Chapter 12). 

For more than 10 years, researchers have investigated different concepts of utilizing microsystems to contact single neurons or whole structures in the central and peripheral nervous system. 

The concept of synaptic transmission postulates the release and subsequent recognition of specific chemical substances by adjacent cellular elements. In the central and peripheral nervous systems, neurons appear to form communication networks where the specificity of information transfer resides in the specific neurotransmitters and the appropriate receptors. Although large number of compounds have been suggested to be neurotransmitters, there seem to be no more than one or two expressed in any one cell type. Specificity appears to lie in the genetic expression of the enzymes necessary for the biosynthesis of each of the substances. 

The primary acute effects of manganese overload (intoxication) are manifested by dysfunction of the central and peripheral nervous systems [512,513], with symptoms that resemble Parkinson s disease and/or psychosis (schizophrenia) muscular rigidity, tremor, ataxia, flat affect, and hallucinations [14, 514-522] Damage to both white and grey matter of the CNS [523-525], as well as to motor neurons [526], has been documented. Chronic exposure to excess manganese (pre-conception, post-conception, and post-natal), by inhalation or other modes, causes developmental problems [527,528], involving especially the nervous system and mucopolysaccharide synthesis. Further studies on the metabolic fate and distribution of orally administered Mn(II) have been described [529]. 

Pathological pain is considered abnormal given that there is no protective value to the organism. This is a morphism in the nervous system that involves plasticity in both the peripheral and central nervous systems. It affects the way the nervous system detects the type of stimuli from the environment - a shift from a normally protective physiological mechanism to an abnormal and possibly pathological mechanism. Consequently, this justifies the concept that pain should be considered a disease process on its own. 

Loewi s work was confined to the autonomic nervous system. Kibjakow (63) and later Dale and his associates tried to extend this concept and suggested that acetylcholine might be the transmitter across ganglionic synapses and at neuromuscular junctions. Their evidence was based essentially on the same type of experiments as was applied in the case of the peripheral autonomic system liberation of acetylcholine after stimulation of preganglionic fibers or motor nerves, stimulation of the sympathetic ganglion and the striated muscle by injection ofij small amounts of ACh, and potentiation of the effects of nerve stimulation by eserinization. The results have been reviewed by Brown (16). 

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