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)

Following spinal cord transection there occurred decreases in Km and Vmax of glutamate decarboxylase (GAD) both above and below the lesion, and an initial decrease in the concentration of GABA. Concomitantly, there was a gradual decrease in presynaptic inhibition. Eight to 12 weeks after spinal cord transection, Km and Vmax for GAD returned to control values, but the GABA content of the spinal cord below the lesion increased significantly and presynaptic inhibition became maximally depressed. These results suggested that during the chronic phase of spinal cord injury there is a decrease in release of GABA, the interneuronal inhibitory neurotransmitter which mediates presynaptic inhibition. Diazepam, a GABA enhancer, increased presynaptic inhibition in acute and chronic spinal cats, this being accompanied by a reduction in somatic muscular spasticity. The degree of this enhancement by diazepam, however, is attenuated with gradual loss of presynaptic inhibition. In the acute cat, a conditioning volley applied to cutaneous afferents blocked the inhibition of the monosynaptic response to extensor motoneurones. In contrast, in chronic spinal cats (eight to 12 weeks), the duration of complete blockade was markedly reduced and was followed by a prolonged period which cutaneous nerve stimulation potentiated the monosynaptic discharge. Similar to GABA, there also occurred an increase of substance P below the level of the lesion. Other neurotransmitters (e.g., norepinephrine, serotonin) accumulated above and disappeared below the transection level. Although somatic msucular spasticity appears to be, to some extent, due to GABA dysfunction in the spinal cord, alterations in "normal" functioning of other neurotransmitters and the loss of supraspinal control also contribute to this state.
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PMID:Correlation of changes in the GABA-ergic system with the development of spasticity in paraplegic cats. 51 79

Sites of action of centrally active muscle relaxant drugs are not well defined. Clinical experience with such drugs suggests that the spinal cord may be one of the important regions from which pathologically increased muscle tone may be relieved. Supraspinal centers that may also be involved in the expression of muscle relaxant action have not yet been defined. We report here that microinjections of therapeutically relevant muscle relaxants into the midbrain tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra is the region from which midazolam, baclofen, and tizanidine (drugs used clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7-phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs active in animal models of spasticity), reduce muscle tone in genetically spastic rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs are topographically restricted to the substantia nigra pars reticulata and are receptor specific. These observations disclose a previously unknown function of the substantia nigra in mediating muscle relaxation.
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PMID:Substantia nigra: a site of action of muscle relaxant drugs. 197 34

We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (I.P.), 5-HT (intrathecally) TRH (I.P. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin-releasing hormone and clonidine on motoneurone excitability. 244 57

The influence of memantine on several properties of a neuronal cell line was tested. The aim was to get some insight into possible mechanisms of action of this drug which is therapeutically applicable in treatment of spasticity, Parkinson's disease, and cerebral coma. In neuroblastoma X glioma hybrid cells, memantine, at micromolar concentrations, blocked the depolarization induced by iontophoretically applied serotonin (5-hydroxytryptamine, 5-HT). In the hybrid cells, receptors of the 5-HT3 type mediated the depolarization, which was frequently accompanied by a series of action potentials. The inhibition by memantine of the serotonin response occurred fast and was completely reversible, irrespective of whether the cell showed a stable membrane potential or spontaneous action potentials. However, memantine did not alter spontaneous or electrically evoked action potential activity in the hybrid cells, and apparently did not block the underlying ionic conductances. Furthermore memantine did not affect either the cation permeability activated by substance P in the hybrid cells or the K+ channel triggered by bradykinin in a glioma cell line. Thus, memantine appears specifically to suppress the ion channel opened by serotonin in the hybrid cells. The interaction of memantine with serotonin receptors and the associated ion channels reported here, might give an important clue, as to a site of action of memantine in the nervous system.
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PMID:Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line. 335 74

We investigated the influence of four substances on the excitability of lumbar motoneurons. These substances, three of which coexist in the same bulbospinal descending pathways that end, for the most part, around motoneurons (MNS), are: 5-hydroxytryptamine (5-HT), substance P (SP) and thyrotropin-releasing hormone (TRH). We also studied the effects of clonidine, an alpha 2 noradrenergic (NA) agonist. This study was carried out in rats spinalized at T5 and treated three weeks earlier with 5-7 dihydroxytryptamine (5-7 DHT). Under these conditions, the following responses were observed: 5-HTP (5-HT precursor) intraperitoneally (I.P.), 5-HT intrathecally (I.T.), TRH (I.P. or I.T.) and substance P (I.T.) all elicited strong excitation of MNS as measured by integrated EMG of the hindlimb muscles; substance P reduced by almost half the response to 5-HTP given one hour and 24 hours later; TRH given acutely did not modify the response to 5-HTP, but given chronically for 21 days markedly increased the response to this substance. Clonidine by itself decreased the excitability of MNS and antagonized the excitatory effects of 5-HTP and TRH. In two separate pilot trials, cyproheptadine, a 5-HTP antagonist, decreased the manifestations of spasticity in a patient with a partial spinal lesion. It would appear that clonidine may have potential use in the management of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin releasing hormone and clonidine on spinal neuron excitability. 754 99

Clinical and animal studies were performed to evaluate the effect of repeated transcutaneous electric nerve stimulation (TENS) applied on acupoints of pain patients and the effect of repeated electroacupuncture (EA) at acupoints of the rat on experimental arthritic pain models. Attempts were also made to evaluate whether substance P (SP), cholecystokinin octopeptide (CCK-8), and met5-enkephalin (MEK) are involved in the mechanism of the cumulative effect of repeated EA on experimental arthritis using neuropharmacological (receptor antagonists) and neurochemical (radioimmunoassay, RIA) approach. The main results show that repeated TENS of 100 Hz relieves spinal spasticity in a cumulative manner, while TENS of 2/15 Hz is effective in relieving chronic pain. In animal chronic pain models, repeated EA suppressed the hyperalgesia in arthritic rats in a cumulative manner. Further studies revealed that in pain patients there was a plastic change in the release and metabolic rate of spinal opioid peptides. In arthritic rats there was also a change in the releasing rate of spinal SP, CCK-8, and MEK as compared to control rats, an effect modulated by repeated EA. These plastic changes occured under chronic pain condition and their modulation by repeated acupoint stimulation may explain the mechanisms of the cumulative effect of acupuncture on chronic pain.
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PMID:[A study on the cumulative effect of repeated electroacupuncture on chronic pain]. 977 64

After spinal cord injury, abnormal responses of spinal cord neurons to sensory input lead to conditions such as autonomic dysreflexia, urinary bladder dyssynergia, muscle spasticity and chronic pain syndromes. These responses suggest that the spinal cord undergoes marked reorganization after an injury. In previous studies, we demonstrated changes in individual patterns of immunoreactivity for growth-associated protein-43, dopamine beta-hydroxylase and substance P that suggest growth and/or changes in expression of neurotransmitter enzymes and peptides in the cord caudal to a transection injury. In the present study we determined whether (i) growth-associated protein-43 and dopamine beta-hydroxylase or substance P were co-expressed in the same neurons prior to cord injury, and (ii) these patterns of expression changed after injury. A change in co-localization patterns caudal to an injury would suggest diversity in responses of different populations of spinal neurons. We used double-labelling immunocytochemistry to determine whether either dopamine beta-hydroxylase or substance P was co-localized with growth-associated protein-43 in control rats and in rats one, two or six weeks after spinal cord transection. We focused on the intermediate gray matter, especially the sympathetic intermediolateral cell column. In control rats, fibres travelling in a stereotyped ladder-like pattern in the thoracic gray matter contained growth-associated protein-43 co-localized with dopamine beta-hydroxylase or substance P. In spinal rats, such co-localization was also observed in spinal cord segments rostral to the cord transection. In contrast, caudal to the transection, substance P and growth-associated protein-43 were found in separate reticular networks. Immunoreactivity for dopamine beta-hydroxylase disappeared in fibres during this time, but was clearly present in somata. Immunoreactivity for growth-associated protein-43 was also found in somata, but never co-localized with that for dopamine beta-hydroxylase. These observations demonstrated co-localization of growth-associated protein-43 with dopamine beta-hydroxylase and substance P in descending spinal cord pathways. Caudal to a cord transection, this co-localization was no longer found, although each substance was present either in an abundant neural network or in somata. One population of spinal neurons responded to cord injury by expressing the growth-associated protein, whereas two others changed in the intensity of their expression of neurotransmitter peptides or enzymes or in the abundance of fibres expressing them. Thus, three populations of spinal neurons had distinct responses to cord injury, two of them increasing their potential input to spinal sensory, sympathetic or motor neurons. Such responses would enhance transmission through spinal pathways after cord injury.
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PMID:Co-localization of substance P and dopamine beta-hydroxylase with growth-associated protein-43 is lost caudal to a spinal cord transection. 1033 36

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost entirely confined to females. After the first six months of life there is developmental slowing with reduced communication and head growth for about one year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures often supervene. Subsequently there is some stabilization in a pseudo-stationary stage during the preschool to school years, associated with more emotional contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dystonia and frequent spasticity but seizures become milder. RS has generally been considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. This protein can bind methylated DNA. Analyses are leading to much further investigation of mutants and their effects on genes. Neuropathological and electrophysiological studies of RS are described. Description of neurometabolic factors includes reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. The results of neuroimaging are surveyed, including volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET).
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PMID:Rett syndrome: review of biological abnormalities. 1125 89

The impressive pain relief experienced by sufferers of dystonia and spasticity from intramuscular injections of botulinum toxin suggested that patients with other chronic, musculoskeletal pain conditions also may benefit. However, there have been relatively few placebo-controlled studies of botulinum toxin in such non-neurologic conditions as myofascial pain syndrome, chronic neck and low back pain, and fibromyalgia; the results of these studies have not been impressive. One explanation for the lack of positive findings may be the lack of clinically evident muscle spasms (overactivity), despite the presence of muscle tenderness, tightness, or trigger points. Clinical observations of pain relief from injections of botulinum toxin for dystonia and spasticity and its apparent efficacy in treating migraine suggest an anti-nociceptive action independent of its neuromuscular junction-blocking action. Evidence from animal experiments supports this notion, and other data provide plausible physiologic mechanisms in the periphery and central nervous systems. These involve modulation of the activity of the neurotransmitters glutamate, substance P, calcitonin gene-related peptide, enkephalins, and others. However, even if botulinum toxin is firmly established as an analgesic, there is insufficient clinical evidence of its efficacy in treating non-neurologic, chronic, musculoskeletal pain conditions.
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PMID:Botulinum toxin for the treatment of musculoskeletal pain and spasm. 1241 5

We review the evidence of botulinum toxins in the treatment of pain. Main indications of botulinum toxin treatment, dystonia and spasticity, involve pain. Increasing evidence suggests direct analgesic effects of botulinum. Botulinum inhibits release of pain mediators (substance P, CGRP, excitatory amino acids, ATP, noradrenaline). Clinical trials have consistently shown analgesic effect of botulinum toxin in post-stroke shoulder pain, bladder dysfunction, chronic migraine, neuropathic pain, bruxism and lateral epicondylitis. Other pain conditions have been studied with yet uncertain results. It seems that the number of patients who would benefit from botulinum toxin treatment will increase considerably in the future.
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PMID:[Botulinum toxins for pain]. 2223 20


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