Central nervous system pain transmission

Endogenous opioid peptide released both in the central nervous system and in other apparatuses of the body that have many regulatory functions, including inhibition of pain transmission. 

The primary counterirritant in group D is capsaicin, a natural substance found in red chili peppers and responsible for the hot, spicy characteristic when used in foods.32,33,48 Capsaicin stimulates the release of substance P from local sensory nerve fibers, depleting substance P stores over time. A period of reduced sensitivity to painful stimuli follows, and transmission of pain impulses to the central nervous system is reduced.42... 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

The ability to control pain and inflammation is an area of continued interest within the pharmaceutical industry. Sensoneuropeptide tachykinins, distributed in the peripheral and central nervous systems, are known to be involved in neurologic inflammation, pain transmission, and broncho-constriction.39 The activation of NK-1 (neurokinin-1), NK-2, and NK-3 receptors can mediate the effects of these tachykinins, resulting in a search for new antagonists as a means of controlling... 

Substance P is an 11-amino-acid peptide amide hormone discovered by von Euler and Gaddum in 1931 (43) from certain tissue extracts, especially from intestinal plain muscles and brains of horses. It is involved in the transmission of pain impulses from peripheral receptors to the central nervous system. It is also involved in the vomit reflex, stimulates salivary secretions, and induces vasodilation. Antagonists seem to have antidepressant properties. 

Diethyl ether was the first general anesthetic used. The dentist Dr. William Morton is credited with its introduction in the 1800s. Diethyl ether functions as an anesthetic by interacting with the central nervous system. It appears that diethyl ether (and many other general anesthetics) functions by accumulating in the lipid material of the nerve cells, thereby interfering with nerve impulse transmission. This results in analgesia, a lessened perception of pain. 

The skeletal muscle ma5 be relaxed by two different groups of drugs, namely first, by those exerting an aetion on the central nervous system (CNS) and used mainly for the relief of painful muscle spasms of spasticity taking place either in neuromuseular or musculoskeletal disorders secondly, those aflfeeting neuromuscular transmission that are employed as adjrmcts in anaesthesia in order to modify the musele relaxation ability. 

Fig. 24.2. Location of endogenous opioid nerve tracts in the central nervous system. Endorphins and opioid receptors in the dorsal horn of the spinal cord, thalamus, and periaqueductal gray (PAG) areas are associated with the transmission of pain signals.

Substance P, an undecapeptide in the central nervous system, is thought to be a neuromodulator for relief and, in higher doses, transmission of pain. Antagonists have been obtained by omitting the first three amino acids and substituting D-enantiomers for proline-4 and tryptophans-7 and -9 (Caranikas et al., 1982). Clinical studies are not available. 

NMDA antagonist [56], has been studied in the treatment of acute and chronic pain [57]. The NMDA receptor has a crucial role in excitatory synaptic transmission, plasticity, and neurodegeneration in the central nervous system [58] and has become an avenue to modulate the excitatory effects of glutamate. 

Analgesics interfere with the generation and/or transmission of impulses following noxious stimulation ( nociception) in the nervous system. This can occur at peripheral and/or central levels of the neuraxis. The therapeutic aim is to diminish the perception of pain. 

Substance P An eleven-amino add neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]... 

Another endogenous peptide which has been implicated in pain transmission and the central integration of pain responses is neurotensin (NeT) (Dobner, 2006 Gui et al., 2004 Pettibone et al., 2002). NeT is a brain-gut tridecapeptide that fulfils a dual function as a neurotransmitter/neuromodulator in the nervous system, and as a paracrine and circulating hormone at the periphery. Three NeT receptors, NTRl,... 

Neurokinins (NK), members of the mammalian tachyldnins. They are widely distributed in the central and peripheral nervous systems, and the two neurokinins (NKA and NKB) act as neurotransmitters or neuromodulators. The biological actions on many tissues are mediated via specific G protein-coupled receptors. Among the three subtypes of NK receptors, NKi is the preferred receptor for substance P. Neurokinin A, NKA (also known as substance K, neurokinin a, and neuromedin L), H-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met -NH2, is the agonist for the NK2 receptor, whereas neurokinin B, NKB (also known as neurokinin and neuromedin K), H-Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met -NH2, mediates its action through the NK3 receptor. Together with substance P, the NK play an important role in pain transmission, neurogenic inflammation, smooth muscle contraction, secretion, vasodilation, and activation of the immune system. The NK were isolated from porcine spinal cord extracts and synthesized by Munekata and coworkers in 1984 [E. Munekata et al., Chem. Lett. 1984, 1013 K. Eolkers et al., Biochem. Biophys. Res. Commun. 1984, 118, 405 J. E. Maggio, Annu. Rev. Neurosci. 1988, 11, 13 Z. Gao,... 

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