Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subpopulation of capsaicin-sensitive cardiac C-fibre afferents co-store calcitonin gene-related peptide (CGRP), substance P and neurokinin A. CGRP exerts positive inotropic and chronotropic effects and is one of the most potent endogenous vasodilators yet discovered. A number of endogenous agents and conditions cause activation of cardiac C-fibre afferents with subsequent local release of CGRP. In myocardial ischaemia with its clinical manifestations angina pectoris and infarction, C-fibre afferents not only convey the sensation of pain, but there is also a local 'efferent' release of CGRP in the heart. After being released, CGRP causes coronary vasodilatation and attenuates the development of myocardial infarction. CGRP may thus represent an endogenous local myocardial protective substance with interesting clinical implications.
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PMID:Potential of calcitonin gene-related peptide in coronary heart disease. 1062 36

Antibody-coated microprobes were inserted into the thoracic (T3-4) spinal cord in urethane-anesthetized Sprague-Dawley rats to detect the differences in the release of immunoreactive substance P-like (irSP) substances in response to differential activation of cardiac nociceptive sensory neurons (CNAN). CNAN were stimulated either by intrapericardial infusion of an inflammatory ischemic exudate solution (IES) containing algogenic substances (i.e., 10 mM each of adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine), or by transient occlusion of the left anterior descending coronary artery (CoAO). There was widespread basal release of irSP from the thoracic spinal cord. Stimulation of the CNAN by IES did not alter the pattern of release of irSP. Conversely, CoAO augmented the release of irSP from T3-4 spinal segments from laminae I-VII. This CoAO-induced irSP release was eliminated after thoracic dorsal rhizotomy. These results indicate that heterogeneous activation of cardiac afferents, as with focal coronary artery occlusion, represents an optimum input for activation of the cardiac neuronal hierarchy and for the resultant perception of angina. Excessive stimulation of cardiac nociceptive afferent neurons elicited during regional coronary artery occlusion involves the release of SP in the thoracic spinal cord and suggests that local spinal cord release of SP may be involved in the neural signaling of angina.
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PMID:Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. 1468 70

Electrostimulatory forms of therapy can reduce angina that arises from activation of cardiac nociceptive afferent fibers during transient ischemia. This study sought to determine the effects of electrical stimulation of left thoracic vagal afferents (C(8)-T(1) level) on the release of putative nociceptive [substance P (SP)] and analgesic [dynorphin (Dyn)] peptides in the dorsal horn at the T(4) spinal level during coronary artery occlusion in urethane-anesthetized Sprague-Dawley rats. Release of Dyn and SP was measured by using antibody-coated microprobes. While Dyn and SP had a basal release, occlusion of the left anterior descending coronary artery only affected SP release, causing an increase from lamina I-VII. Left vagal stimulation increased Dyn release, inhibited basal SP release, and blunted the coronary artery occlusion-induced release of SP. Dyn release reflected activation of descending pathways in the thoracic spinal cord, because vagal afferent stimulation still increased the release of Dyn after bilateral dorsal rhizotomy of T(2)-T(5). These results indicate that electrostimulatory therapy, using vagal afferent excitation, may induce analgesia, in part, via inhibition of the release of SP in the spinal cord, possibly through a Dyn-mediated neuronal interaction.
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PMID:Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia. 1529 64

Adenosine 5'-triphosphate (ATP) is implicated in peripheral pain signaling through activation of P2X receptors. P2X(3) receptors have a high level of expression in, and selective location on sensory afferents. P2X receptors, particularly the P2X(3) subtype, are identified as targets for novel analgesics. The stellate ganglion (SG) is peripheral sympathetic ganglia involved in heart function. Surgical interventions of sympathetic afferent pathways abolish or relieve angina pectoris, so it is showed that cardiac pain is mediated by the activation of afferents in sympathetic nerves. The cervicothoracic sympathetic ganglia, including the stellate ganglion, are implicated in sensations associated with myocardial ischemia or cardiac pain. In the present study we have examined P2X(3) involvement in cardiac nociceptive transmission. P2X receptor agonists activated currents (I(ATP)) in SG neurons. The I(ATP) amplitude and P2X(3) mRNA expression in myocardial ischemic injury group were much larger than those obtained in control group. Prostaglandin E(2) (PGE(2)) and substance P (SP) increased ATP-activated currents. P2X(3) receptor antagonist A-317491 reduced P2X agonist activated currents and P2X(3) mRNA expression. The results revealed that the myocardial ischemia induced the upregulation of P2X(3) receptor in function and morphous and P2X(3) receptor antagonist A-317491 inhibited P2X agonist activated currents and P2X(3) mRNA expression. The facts indicated that P2X(3) receptor in SG neurons was involved in cardiac nociceptive transmission.
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PMID:Myocardial ischemic nociceptive signaling mediated by P2X3 receptor in rat stellate ganglion neurons. 1815 99

Spinal cord stimulation (SCS) is an established treatment for intractable neuropathic pain. SCS is performed using an implantable pulse generator connected to leads with electrodes positioned in the dorsal epidural space, which are then used to stimulate the ascending and descending dorsal column fibres to achieve paresthesia covering the area of pain. It is based on the Gate Control Theory, introduced by Melzack and Wall in 1965, which suggests that stimulation of large afferent fibres can inhibit pain transmission at the level of the dorsal horns. More recent studies indicate that SCS releases substance P serotonin, noradrenaline and GABA in the dorsal horns; activation of the GABAB receptor may be linked to a decrease in the release of glutamate and other excitatory amino acids, resulting in a decrease of neuropathic pain. The clinical indications for SCS are mainly peripheral vascular diseases (PVD), refractory angina, failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS) type 1 and type 2, spinal cord stenosis and neuropathic pain. The new puncture trial method is less invasive and can reduce psychological resistance of the patient for SCS manipulation.
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PMID:[Spinal cord stimulation]. 1992 6

Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.
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PMID:Mechanisms of cardiac pain. 2588 May 19


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