Neurotransmitters pain initiation

The surrounding redness caused by the vasodilatation of local blood vessels in the skin (hyperaemia). Histamine released at the site of contact acts on sensory nerve endings in the skin. Impluses travel along the axon to other peripheral branches of the same neuron to cause release of vasodilataory peptide neurotransmitters from nerve endings serving a wider area of skin than the initial contact point. Impluses reaching the CNS are interpreted as itch and pain. 

How the different neurotransmitters may be involved in the initiation and maintenance of some brain disorders, such as Parkinson s disease, epilepsy, schizophrenia, depression, anxiety and dementia, as well as in the sensation of pain, is then evaluated and an attempt made to see how the drugs which are used in these conditions produce their effect by modifying appropriate neurotransmitter function (section C). The final section (D) deals with how neurotransmitters are involved in sleep and consciousness and in the social problems of drug use and abuse. 

Initially, Gly was described to be restricted to the mammalian spinal cord, but subsequently it has been detected supraspinally as well (Legendre, 2001). Gly receptors (GlyRs) belong to the superfamily of receptor channels, which are generally composed of five subunits (al-4, P) (Webb and Lynch, 2007). The different a-and P-subunits are differently localized. The GlyR is a pentameric chloride channel, and it is classically known for mediating inhibitory synaptic transmission between interneurons and motor neurons in reflex circuits of the spinal cord, but they are also found presynaptically, where they modulate neurotransmitter release (Lynch, 2009 Webb and Lynch, 2007). The picture is complicated by the fact that Gly also binds to and activates NMDA receptors, therefore, it can influence the pain threshold by this action as well (see above. Section 2.3.1) (Zeilhofer, 2005). 

SYMPTOMATIC THERAPY OF ALS SPASTICITY Spasticity is a clinical feature of ALS that often leads to considerable pain and discomfort and reduces mobility, which already is compromised by weakness. Furthermore, spasticity is the feature of ALS that is most amenable to present forms of treatment. Spasticity is an increase in muscle tone characterized by an initial resistance to passive displacement of a limb at a joint, followed by a sudden relaxation (the so-caUed clasped-knife phenomenon). Spasticity is the result of the loss of descending inputs to the spinal motor neurons, and the character of the spasticity depends on which nervous system pathways are affected. Whole repertoires of movement can be generated directly at the spinal cord level it is beyond the scope of this chapter to describe these in detail. In general, pyramidal pathways that use glutamate as a neurotransmitter are impaired, with relative preservation of the other descending pathways, resulting in hyperactive deep-tendon reflexes, impaired fine motor coordination, increased extensor tone in the legs, and increased flexor tone in the arms. The gag reflex often is overactive as well. 

The excitatory neurotransmitter glutamate (Figure 108.2) has a variety of family members that have been evaluated as targets for analgesic development especially in the initiation and maintenance of neuropathic pain resulting from central injury (spinal cord), peripheral injury (PDN, radiculopathy), and inflammatory injury (arthritis). 

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