Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P-Chlorophenylalanine (PCPA) 250 mg/kg IP, was given to a group of rats. 72 hrs later the electro-acupuncture analgesia was tested and substance P (SP) in the brain stem and the lumbar spinal of the rats was determined by RIA. After PCPA injecting the electro-acupuncture no longer caused analgesia but lowered the pain threshold. Meanwhile the level of SP in the brain stem and lumbar spinal did not increased but much lowered than the group of vehicle injection combined with electro-acupuncture. It suggests that by PCPA depleting the 5-HT in CNS and abating the 5-HT-energic descending inhibition the electro-acupuncture no longer causes analgesia but promotes the SP transmitted release. It further suggests that in lower brain stem and spinal transmission of SP was regulated by descending inhibition. Analgesia of electro-acupuncture activates the 5-HT-energic descending inhibition and decreases the nociceptive transmission of SP partly.
 ...
PMID:[The influence of P-chlorophenylalanine on the analgesia of electro-acupuncture and the level of SP in CNS of rats]. 170 62

The present work was carried out to observe the effect of intra-cerebroventricular (icv) injection of monoamine neurotransmitters, enkephalin and morphine on immunoreactive substance P(Ir-SP) contents in hypothalamus, striatum, hippocampus and pain threshold. The results were as follows: (1) After icv or intra-DR (dorsal raphe nucleus) injection of 5-HTP, the content of Ir-SP in hypothalamus significantly decreased and pain threshold markedly increased; After depletion of the 5-HT content in brain by pCPA or destruction of DR, the contents of Ir-SP were remarkably elevated in three brain regions by the former and in hypothalamus, striatum by the later. (2) The Ir-SP levels in the three brain regions and the pain threshold were not affected by the icv injection of NE, however, icv injection of DA caused a increase of Ir-SP concentration in striatum which was reversed by the DA receptor antagonist haloperidol, but without any change of the pain threshold. 7th day after icv injection of 6-OHDA, the content of Ir-SP in striatum significantly reduced. (3) Icv injection of met-enkephalin (MEK) or morphine could increase the Ir-SP levels in hypothalamus, striatum and the pain threshold, and above-mentioned effect of morphine could be prevented by the opioid receptor antagonist naloxone. Icv injection of leu-enkephalin (LEK) had no effects both on Ir-SP contents in three brain regions and the pain threshold.
 ...
PMID:[Effect of monoamine neurotransmitters, enkephalin and morphine on substance P contents of several brain regions and pain threshold in rats]. 170 64

The purpose of this study is to observe the effect of intracerebroventricular (icv) and intra-PAG injection of substance P (SP) on serotonin (5-HT) contents of hypothalamus, hippocampus, striatum and its relation with the change of pain threshold, electroacupuncture (EA) analgesia. The results were as follows: (1) After icv injection of SP, the pain threshold and the 5-HT contents of hypothalamus, hippocampus were significantly increased. After depletion of the 5-HT contents in brain by pCPA, the inhibitor of 5-HT synthesis, the effect of SP on elevating pain threshold and the 5-HT contents of hypothalamus, hippocampus were markedly attenuated, bud did not prevent the analgesic effect of SP (2) The pain threshold and the 5-HT contents of hypothalamus, hippocampus were dose-dependently increased by intra-PAG injection of SP. (3) The intra-PAG injection of SP introduced simultaneously with high or low frequency EA did not affect the change of 5-HT contents of three brain regions, but caused a more marked elevation of pain threshold. These results suggest that the serotoninergic system may be activated by PAG for the mediation of SP induced analgesia. There is a synergic action of analgesia between the effects produced by intra-PAG injection of SP and those by high or low frequency EA.
 ...
PMID:[Effect of intracerebral injection of substance P on serotonin contents of several brain regions and its relation with pain threshold, electroacupuncture analgesia in rats]. 171 75

Rats were fed an artificial diet containing either their normal, or five times their normal, daily requirement of tryptophan for up to five weeks and were tested in an animal model of deafferentation pain, nerve lesion-induced autotomy. In this model one of the hind limbs of the animal was denervated, and the extent to which the animal attacked its denervated paw was assessed. Rats receiving the high-tryptophan diet showed significantly lower levels of autotomy, compared to rats fed the control diet. 5-Hydroxytryptamine and 5-hydroxyindoleacetic acid in the brain and spinal cord were significantly elevated in rats receiving the high-tryptophan diet, indicating that the supplemented diet produced a chronic increase in CNS indoleamine metabolism. Currently there is no accepted pharmacological treatment of deafferentiation pain. Our results suggest that tryptophan should be tested in phantom limb pain and other deafferentation pain syndromes.
 ...
PMID:The effect of tryptophan supplementation on autotomy induced by nerve lesions in rats. 172 16

5-Hydroxytryptamine (5-HT) is present throughout the gastrointestinal tract, which acts as the major reservoir of this substance in the body. Its physiologic role has not been clearly established, although it seems likely that 5-HT is involved in the regulation of aspects of intestinal motility such as peristalsis and the migrating motor complex. In disease states the contribution of 5-HT is perhaps more clearly established, particularly its role in chemotherapy-induced emesis, in the carcinoid syndrome, and, possibly, in mediating the effect of some intestinal secretagogues, notably cholera toxin. Many of the functions of 5-HT in the gut have been elucidated as a result of the development of antagonists to 5-HT receptors. However, some of these compounds have 5-HT agonist activity as well as 5-HT receptor blocking activity, making interpretation of their effects in health and disease difficult. Nevertheless, 5-HT receptor antagonists are finding an important place in the management of the carcinoid syndrome and in chemotherapy-induced emesis and may well evolve as important agents for modulating gut motility and for inhibiting secretory states in the small and large intestine. The suggestion that 5-HT3 receptor antagonists might also modulate visceral sensation in the gut is of great interest because of their potential to relieve symptoms of functional bowel disorders such as pain, urgency, and bowel frequency.
 ...
PMID:5-Hydroxytryptamine and 5-hydroxytryptamine-3 receptor antagonists. 177 47

In those subjects genetically susceptible to migraine, biological rhythms or excessive afferent stimulation trigger an episodic neurovascular reaction with focal neurological symptoms, headache and nausea as its most common manifestations. Mood changes and a craving for sweet foods point to a preliminary hypothalamic disturbance. The referral of ice-cream headache and ice-pick pains to the habitual site of migraine headache (even in the intervals between attacks) indicate defective control of trigeminal pathways. Laboratory experiments have demonstrated that projections from the brainstem, releasing monoamines and peptides as transmitter agents, can mimic the vascular changes of migraine. Serotonin released from platelets may sensitize vessels to respond to distension by generating pain-producing afferent discharges. Central depletion of monoamines can accentuate the perception of pain by reducing the efficacy of the endogenous pain control system. The intravenous injection of serotonin relieves migraine headache but produces side-effects. A new drug, sumatriptan, acting on a subtype of serotonin receptors, the 5HT1-like receptor, is undergoing clinical trial for the relief of acute attacks of migraine. Antagonist of the 5HT2 receptor are beneficial in interval therapy for the prevention of migraine. Increased knowledge of physiological mechanisms and neurotransmitters that can mediate the various components of the migraine attack opens the way for improvements in pharmacotherapy.
 ...
PMID:[Physiopathology of migraine]. 196 76

The major finding of this analysis is that acute anti-migraine agents (e.g., ergots, sumatriptan) share high affinity for 5-HT1D receptors. This receptor appears to be present in certain intracranial blood vessels. It is also found on nerve terminals where it inhibits the release of 5-HT and other neurotransmitters. Theoretically, 5-HT1D receptor agonists may acutely inhibit the release of vasoactive and/or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In contrast, a number of prophylactic anti-migraine drugs share a relatively high affinity for 5-HT2 receptors in human brain. Although this receptor is also found in certain blood vessels, it is present throughout the nervous system. The receptor appears to mediate neuronal depolarizations at the cellular level. No hypothesis, at present, readily explains the effectiveness of prophylactic anti-migraine drugs based on this receptor. These data offer a novel approach to the analysis of anti-migraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. "Pure" drugs could be chosen which would essentially limit the number of possible sites of action for the drugs. For example, an agent which displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of the specific 5-HT receptor site in the pathogenesis of migraine. Further attempts to determine a common mechanism of action for effective anti-migraine agents should facilitate the elucidation of the pathogenesis of this neurological syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The pharmacology of current anti-migraine drugs. 196 55

This study examined whether the antinociception produced following the intrathecal (i.t.) administration of serotonin (5-hydroxytryptamine, 5-HT) and other 5-HT receptor agonists in a model of visceral pain that utilizes colorectal distension (CRD) as the noxious visceral stimulus is mediated through interaction with spinal 5-HT1, 5-HT2, or 5-HT3 receptor subtypes. CRD in conscious rats reliably elicits two pseudaffective reflexes: a vigorous pressor response and a visceromotor response. Antinociception is characterized by inhibition of both pseudaffective responses. The effects of 5-HT receptor agonists and antagonists on resting blood pressure were also examined. The i.t. administration of 5-HT resulted in a dose-dependent elevation of the visceromotor threshold and inhibition of the pressor response to CRD. The 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B receptor agonist RU-24969, the 5-HT2 receptor agonists DOI, MK-212 and alpha-methyl-5-HT and the 5-HT3 agonist 2-methyl-5-HT all dose-dependently inhibited the pressor response and dose-dependently elevated the visceromotor threshold to noxious CRD. The rank order of potency of these agonists was the same for both pseudaffective responses to CRD: DOI greater than or equal to 8-OH-DPAT greater than or equal to MK-212 = RU-24969 greater than or equal to alpha-methyl-5-HT = 2-methyl-5-HT much greater than 5-HT. The antinociceptive effects of 5-HT, RU-24969, alpha-methyl-5-HT and DOI were antagonized by i.t. pretreatment with methysergide. Intrathecal pretreatment with ketanserin antagonized the antinociceptive effects of MK-212 and MDL-72222 antagonized the effects produced by 2-methyl-5-HT in response to CRD. The antinociceptive effects produced by 8-OH-DPAT were not antagonized by i.t. pretreatment with methysergide. These results demonstrate that 5-HT1, 5-HT2 and 5-HT3 receptors in the spinal cord mediate antinociception in response to noxious CRD in conscious rats.
 ...
PMID:Evidence that spinal 5-HT1, 5-HT2 and 5-HT3 receptor subtypes modulate responses to noxious colorectal distension in the rat. 201 33

Serotonin is widely distributed throughout the central nervous system and is implicated in a variety of neural functions such as pain, feeding, sleep, sexual behavior, cardiac regulation and cognition. This paper is concerned with the last of these. Abnormalities of the serotonergic nervous system are well documented in pathologic studies of Alzheimer's disease and there is evidence suggesting that changes in this system occur in association with non-disease aging. Data on the role of serotonin in learning and memory and on the effects of aging on brain serotonin function are reviewed and discussed in relation to pharmacologic treatment strategies for the memory impairments associated with advancing age.
 ...
PMID:Serotonin, memory, and the aging brain. 202 16

The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have recently been carried out on rats and guinea-pigs into the effects of antimigraine agents, including ergot alkaloids, sumatriptan and non-steroidal anti-inflammatory drugs (NSAIDs), on neurogenic plasma protein extravasation in the dura mater induced by electrical stimulation of trigeminal ganglia or systemic administration of capsaicin. It is known that the dura mater is able to produce headaches in man. Ergot alkaloids have been shown to block neurogenic inflammation via a C-fibre dependent neuronal mechanism. Sumatriptan appears to act fairly similarly although, whereas the ergot alkaloids are non-selective for either 5-hydroxytryptamine (5-HT; serotonin) receptors or 5-HT1, sumatriptan is selective for 5-HT1 receptors. The antimigraine action of NSAIDs may be via either an effect on blood vessels or an effect on the nerve fibre. The antimigraine effects of ergot alkaloids, sumatriptan and NSAIDs are discussed in the light of the common vasoconstrictor actions of these agents and knowledge that vasodilatation is apparently not responsible for migraine headache pain in most cases.
 ...
PMID:Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions. 204 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>