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)

For 20 years botulinum toxin A has been used for the treatment of a variety of disorders characterised by pathologically increased muscle contraction. Recently, treatment of tension headache, migraine, cluster headache, and myofascial pain syndromes of neck, shoulder girdle, and back with botulinum toxin A has become a rapidly expanding new field of research. Several modes of action are discussed for these indications. The blockade of cholinergic innervation reduces muscular hyperactivity for 3 to 6 months. Degenerative changes in the musculoskeletal system of the head and neck are prevented. Nociceptive afferences and blood vessels of the pericranial muscles are decompressed and muscular trigger points and tender points are resolved. The normalisation of muscle spindle activity leads to a normalisation of muscle tone and central control mechanisms of muscle activity. Oromandibular dysfunction is eliminated and muscular stress removed. However, the effect of botulinum toxin A cannot be explained by muscular actions only. Its retrograde uptake into the central nervous system modulates the expression of substance P and enkephalins in the spinal cord and nucleus raphe. Recent findings suggest an inhibition of sterile inflammation which may lead to a blockade of the neurogenic inflammation believed to be the pathophysiological substrate of primary headache disorders. The efficacy of botulinum toxin A in the treatment of pain disorders is being investigated in several studies at the moment. The results and experiences obtained so far present new alternatives in the treatment of chronic pain disorders. The practical use of botulinum toxin A is demonstrated.
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PMID:[Botulinum toxin A for the treatment of headache disorders and pericranial pain syndromes]. 1132 Aug 61

The mild vasoconstrictor effects of modern antimigraine drugs, such as serotonin (5-HT; 5-hydroxytryptamine)1B/D agonists, have led to a search for nonvasoconstrictor approaches to therapy. Such approaches have included substance P (neurokinin I) antagonists, endothelin antagonists and highly specific 5HT1D agonists. All of these substances are effective in animal models and have no significant vasoconstrictive effects. However, all of them failed to demonstrate any antimigraine effects. Current clinical and experimental evidence therefore supports the view that isolated peripheral trigeminal nerve inhibition is insufficient to relieve acute migraine.
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PMID:Pharmacological opportunities and pitfalls in the therapy of migraine. 1137 57

This article provides a brief overview of the history of substance P from its discovery in the 1930s to the present day. The development of substance P receptor agonists and antagonists, and more recently the employment of transgenic mice, provide a framework to explore the functional role of substance P. Chronic inflammation and pain are associated with a number of diseases, and it has been proposed that substance P, released from primary afferent nerve endings play a role in these conditions. Recent developments with substance P antagonists have demonstrated the importance of substance P in several models of disease that span from asthma to chronic bronchitis; from cystitis, inflammatory bowel disease to migraine; emesis, depression, pain and seizures. Advancements in the knowledge of the role of substance P, its agonists and antagonists could provide clinical solutions for a variety of chronic inflammatory conditions.
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PMID:Substance p. 1137 38

Evidence from animals and humans suggests that brainstem nuclei such as the raphe nuclei, the locus coeruleus (LC) and the periaqueductal grey matter (PAG), are involved in the pathophysiology of migraine. In order to understand possible neurotransmitters involved we have, by means of indirect immunocytochemistry, analysed these regions for the occurrence and distribution of calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate-cyclase activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP). CGRP-immunoreactive (-ir) cell bodies, but no fibres, were found to occur in high numbers, constituting 80% of all nerve cell bodies in the LC. A smaller number of these nerve cell bodies (40%) in the LC proved to be PACAP-ir. The LC neurones also stored the vesicular monoamine transporter (VMAT)- and the C-terminal flanking peptide of neuropeptide Y (C-PON)-ir, illustrating their adrenergic nature. Double immunostaining revealed that all VMAT-and C-PON-containing neurones, in addition, stored CGRP. Immunoreactive cell bodies were not seen in the nucleus raphe magnus (NRM) or PAG. Numerous SP-ir nerve fibres were observed in the NRM, the LC and the PAG. Few PACAP-ir nerve fibres were detected in the PAG and few VIP-ir nerve fibres were seen in the NRM and the PAG.
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PMID:Neuropeptide localization in the "migraine generator" region of the human brainstem. 1142 90

Vasodilatation in the dura mater has been implicated in migraine pathogenesis. Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles. Previous studies suggest that calcitonin gene-related peptide (CGRP) released from Adelta-fibres plays a more important role than substance P (SP) released from C-fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the present study, the relationship between CGRP and 5-HT1B/1D receptors, and between CGRP and SP in the trigeminal ganglion neurons in rats was examined by double immunohistochemical staining. CGRP, 5-HT1B, 5-HT1D and SP-positive trigeminal ganglion neurons were all predominantly small and medium-sized. In the trigeminal ganglia, approximately 50% of CGRP-positive neurons were 5-HT1B positive. Similarly, approximately 55% of CGRP-positive neurons were 5-HT1D immunoreactive. Approximately 50% of CGRP-positive neurons were SP-positive, while 93% of SP-positive neurons were CGRP-positive, suggesting that nearly all SP-positive neurons also contain CGRP. The fibre types of the 5-HT1B- and 5-HT1D-positive neurons were further investigated with an antibody against the A-fibre marker 200-kDa neurofilaments (NF200). Approximately 46% of the 5-HT1B-positive and 43% of the 5-HT1D-positive trigeminal ganglion neurons were also NF200 positive, indicating that many A-fibre trigeminal neurons express 5-HT1B or 5-HT1D receptors. These results support the hypothesis that one important action of antimigraine drugs is the inhibition of CGRP release and that Adelta-fibres may play an important role in migraine pathogenesis.
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PMID:Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats. 1142 50

5-Hydroxytryptamine (5-HT) is implicated in migraine and agonist directed against 5-HT(1B) and 5-HT(1D) receptors are commonly used as effective therapies. The antimigraine mechanisms involve the inhibition of intracranial sensory neuropeptide release. In order to determine which 5-HT(1) receptor subtypes are involved we have by immunocytochemistry examined the distribution of 5-HT(1B) and 5-HT(1D) receptors in the human trigeminal ganglia, and addressed which of them colocalize with calcitonin gene-related peptide (CGRP), substance P (SP) or nitric oxide synthase (NOS). We detected that 5-HT(1D) receptor immunoreactivity (i.r.) was predominantly expressed in medium-sized cells (86% of positive cells, 30-60 microm). About 9% of the 5-HT(1D) receptor i.r. cells were large in size (> 60 microm) and 5% were small in size (< 30 microm). In a similar pattern, 5-HT(1B) receptor i.r. was mainly expressed in medium-sized cells (81% in 30-60 microm, 15% in > 60 microm and 4% in < 30 microm). Double immunostaining was used to determine whether the 5-HT(1B) or 5-HT(1D) receptor immunoreactive cells co-localized with either CGRP, SP or NOS. Thus, 89% of the CGRP i.r. cells expressed 5-HT(1D) receptor i.r. and 65% of the CGRP positive cells were 5-HT(1B) receptor positive. Most of the 5-HT(1D) (95%) and the 5-HT(1B) (94%) receptor i.r. cells showed SP immunostaining and 83% of 5-HT(1D) receptor and 86% of 5-HT(1B) receptor i.r. cells contained NOS. In conclusion, both 5-HT(1B) and 5-HT(1D) receptors are expressed in the human trigeminal ganglion and they are mainly localized in medium-sized cells and they seem to colocalize with CGRP, SP and NOS.
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PMID:5-HT(1B) and 5-HT(1D) receptors in the human trigeminal ganglion: co-localization with calcitonin gene-related peptide, substance P and nitric oxide synthase. 1147 27

Prior studies have suggested a common etiology involved in Tourette's syndrome and several comorbid conditions and symptomatology. Reportedly, current medications used in Tourette's syndrome have intolerable side-effects or are ineffective for many patients. After thoroughly researching the literature, I hypothesize that magnesium deficiency may be the central precipitating event and common pathway for the subsequent biochemical effects on substance P, kynurenine, NMDA receptors, and vitamin B6 that may result in the symptomatology of Tourette's syndrome and several reported comorbid conditions. These comorbid conditions and symptomatology include allergy, asthma, autism, attention deficit hyperactivity disorder, obsessive compulsive disorder, coprolalia, copropraxia, anxiety, depression, restless leg syndrome, migraine, self-injurious behavior, autoimmunity, rage, bruxism, seizure, heart arrhythmia, heightened sensitivity to sensory stimuli, and an exaggerated startle response. Common possible environmental and genetic factors are discussed, as well as biochemical mechanisms. Clinical studies to determine the medical efficacy for a comprehensive magnesium treatment option for Tourette's syndrome need to be conducted to make this relatively safe, low side-effect treatment option available to doctors and their patients.
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PMID:The central role of magnesium deficiency in Tourette's syndrome: causal relationships between magnesium deficiency, altered biochemical pathways and symptoms relating to Tourette's syndrome and several reported comorbid conditions. 1186 98

Substance P (SP) is a neuropeptide which is abundant in the periphery and the central nervous system, where it is colocalized with other neurotransmitters such as serotonin or dopamine. SP has been proposed to play a role in the regulation of pain including migraine and fibromyalgia, asthma, inflammatory bowel disease, emesis, psoriasis as well as in central nervous system disorders. This review summarizes our current knowledge of the role of SP in the pathogenesis of neuropsychiatric disorders with special emphasis on affective disorders including bipolar disorders. It also reviews current treatment approaches with neurokinin 1 receptor antagonists which appear to be promising drugs for the future treatment of affective disorders.
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PMID:Substance P and affective disorders: new treatment opportunities by neurokinin 1 receptor antagonists? 1189 70

In migraine and other primary headaches there is a strong vascular component. Besides the trigeminovascular components some of the associated symptoms point to the involvement of brain stem regions. The central limb of the trigeminal vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and to the C1-C2 levels of the spinal cord. The aim of the present study was to demonstrate the occurrence of some neurotransmitters in these regions in man. In both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1 and C2 levels there were numerous substance P immunoreactive fibres. Fibres containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) were moderately dense in number. Fibres containing vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen in the TNC or at the C1 and C2 levels of the spinal cord.
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PMID:Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2. 1197 78

Neurogenic inflammation is elicited by activation of unmyelinated sensory neurons through noxious stimuli and subsequent release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. The nerve-mediated inflammatory responses in the tissue consist of hyperaemia and oedema which under some circumstances may be accompanied by pain. Neurogenic inflammation has been implicated in the pathophysiology of various human diseases with uncertain etiology. Signs of inflammation and hyperalgesia associated with chronic pain syndromes such as migraine, arthritis and complex regional pain syndrome resemble the characteristics of neurogenic inflammation. By extrapolation of convincing evidence obtained in rodent models, neurogenic inflammation is assumed to contribute to diseases of the respiratory system, gastrointestinal tract, urogenital tract, and skin in humans. Since, however, highly selective substance P receptor antagonists, found to be effective against inflammation in rodents, failed to inhibit inflammatory processes in clinical trials, the hypothesis of an involvement of neurogenic inflammation in human diseases is discussed critically in this review. Beyond its primarily inflammatory character neurogenic inflammation can be regarded as a mechanism that activates protective responses, thus bringing about a first line of defence to maintain the integrity of the tissue and to contribute to tissue repair.
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PMID:[Neurogenic inflammation. II. pathophysiology and clinical implications]. 1210 11


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