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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of a relationship between inhibition of prostaglandin biosynthesis and analgesic or anti-inflammatory activity was investigated in the case of the non-narcotic analgesics glafenine, floctafenine and clometacine, in comparison to indomethacin and acetylsalicylic acid. These compounds inhibit prostaglandin biosynthesis from arachidonic acid in a guinea-pig lung homogenate as strongly as indomethacin. On its biosynthesis in rat epididymal tissue stimulated by noradrenaline, glafenine equals indomethacin inhibitory potency, whereas floctafenine and clometacine are less active. Acetylsalicylic acid is the least active in both preparations. In vivo, prostaglandin biosynthesis induced in rat peritoneal fluid by injection of acetic acid is inhibited by the 5 drugs, ranked as follows: floctafenine greater than indomethacin greater than glafenine greater than clometacine greater than acetylsalicylic acid. The pharmacological profile of glafenine, floctafenine and clometacine is characterized by a relatively strong effect on acetic acid writhing and a relatively weak effect on carrageenin oedema, U.V. erythema and adjuvant arthritis. The inhibition of prostaglandin biosynthesis seems better correlated with their analgesic activity than with their anti-inflammatory effects. The results show that prostaglandins could play an important role in the genesis of tissulary pain in animals.
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PMID:Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs. 1 49

The effect of alpha-adrenolytics: phenoxybenzamine, phentolamine, aceperone, dihydroegotamine, and yohimbine, was tested on reactivity to pain, and on the analgesic action of morphine and pethidine in albino mice. The compounds exert an analgesic effect by themselves, and potentiate the analgesic action of threshold doses of morphine and pethidine. The results seem to provide another proof that the cerbral noradrenaline neurons participate in central mechanisms of pain perception.
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PMID:Analgesic action of alpha-adrenolytics in albino mice. 1 52

The roles played by the cerebral monoamines (dopamine, noradrenaline and serotonin) in stimulation-produced analgesia (SPA) have been investigated in the rat employing the tail flick test. SPA was elicited through bipolar electrodes chronically implanted in the mesencephalic periaqeductal gray matter, an area previously shown to yield potent and reliable analgesic effects. Four approaches were used to alter transmission in monoamine pathways. (1) Depletion of monoamines by administration of tetrabenazine (TBZ), p-chlorophenylalanine (PCPA), alpha-methyl-para-tyrosine (AMPT), or disulfiram. (2) Replacement of depleted monoamine stores by appropiate precursors (5-HTP or L-DOPA) in combination with a peripheral decarboxylase inhibitor. (3) Potentiation of monoamine systems by administration of precursors to previously untreated animals or by administration of a dopamine receptor stimulator, apomorphine. (4) Blockade of catecholamine receptors by haloperidol or of dopamine receptors by pimozide. These four approaches yielded internally consistent results. Depletion of all 3 monoamines (TBZ) led to a powerful inhibition of SPA. Original levels of SPA were restored by injection of either 5-HTP or L-DOPA. Specific depletion of serotonin (PCPA) caused a reduction in SPA, whereas elevation of serotonin levels (5-HTP) caused an increase in SPA. Dopamine receptor blockade (pimozide) decreased SPA, whereas the precursor (L-DOPA) and a dopamine receptor stimulator (apomorphine) increased SPA. On the other hand, selective depletion of noradrenaline (disulfiram) caused an increase in SPA; and at a time when noradrenaline levels are depressed and dopamine levels are elevated (AMPT + L-DOPA), SPA was seen to be particularly enhanced. thus, dopamine and serotonin appear to facilitate SPA, whereas noradrenaline appears to inhibit it. When a general catecholamine receptor blocker (haloperidol) was employed, SPA was diminished, suggesting that the influence of dopamine in SPA is greater than that of noradrenaline. Most of the drugs used in this study significantly altered SPA at doses which left baseline tail flick latency unaffected. It would appear, therefore, that SPA has a neural substrate at least partly independent of that underlying baseline pain responsiveness. Consideration is given to various ascending and descending monoamine system as possible component paths in this neural substrate of SPA. Finally, the present results are discussed in relation to studies by others on the site and mechanism of morphine's analgesic action. Some striking parallels between SPA and morphine analgesia are noted. These suggest the existence of a common pain-inhibitory system in the brain activated by morphine and by focal electrical stimulation.
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PMID:Monoaminergic mechanisms of stimulation-produced analgesia. 12 41

A multiple stimulus (secondary or repetitive stimulus) to the sensory nerve endings in the skin and in the connective subcutaneous tissue is exerted by acupuncture. Because of the tight interlacing of nerve endings, this stimulus affects simultaneously the sensory fibres of both the cerebrospinal nerve, the Sympathicus and the Parasympathicus. The slow conducting pain fibres (C-fibres) are inhibited in their function by the fast conducting Abeta-fibres and Adelta-fibres, which transmit pressure, vibration and electric currents (Foerster, Zottermann). In addition a secondary stimulus inhibits or modulates a peripheral pain stimulus (pain of operation) in various synapses on the sensory pathway to the cortex, especially in the substantia gelatinosa of the spinal cord. According to Keidel, Raich and Albrecht pain stimuli are masked up to 50% by vibration and other "rivaling" stimuli. Furthermore, acupuncture releases a higher level of Noradrenaline and Serotonine in the liquor of ventricles. These two biogenic amines effect also an analgesia such as demonstrated in animals by artificial injection in the ventricles. The author gives also a detailed review about the importance of the transmitters noradrenaline, serotonine and acteylcholine for the acupuntural analgesia.
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PMID:[On a neurophysiological interpretation of acupunctural analgesia in tonsillectomy and in extensive operations (author's transl)]. 12 4

Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms. Chlorpromazine, atropine and p-chlorophenylalanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the thresholds for vocalisation only. Yohimbine decreased clonidine activity at both thresholds while 5-HTP and alpha-methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied. It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine. The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin these functional responses after clonidine is also discussed.
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PMID:Clonidine antinociceptive activity: effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat. 13 92

Brain catecholamine metabolism was monitored by distribution of labelled noradrenaline (3H-NA) after intraventricular injection to intact and adrenalectomized rats. The adrenalectomy produced an increased disappearance rate of the labelled pool in the hypothalamus, hippocampus and neocortex. These changes could be prevented by hydrocortisone pretreatment. Painful stimuli resulted in an increased disappearance of the labelled pool in both intact and adrenalectomized rats. The implantation of hydrocortisone into the tuberoinfundibular region prevented the stress-induced changes of the catecholamine metabolism. Intraventricular administration of ACTH1-24 and ACTH4-10 produced a significant increase of the disappearance rate in different brain regions of adrenalectomized rats. The blocking of catecholamine synthesis by intraventricular injection of alpha-methyl-m-tyrosine resulted in a marked decrease of the labelled pool but did not prevent the ACTH-induced decrease of the tracer pool. On the other hand, the blocking of monoamine-oxydase activity by Pargyline led to a marked increase of the labelled pool but intraventricular administration of ACTH led to an increase of the disappearance rate. The mechanism of ACTH action on brain catecholamine metabolism is still obscure, however, an increased release of the NA to ACTH peptides is very likely in the light of the present observations.
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PMID:Effect of ACTH and its fragment on brain catecholamines in intact and adrenalectomized rats. 18 19

Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses.
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PMID:Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats. 20 66

In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.
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PMID:Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT. 23 55

The effect of serotonin and noadrenaline precursors on the training of the animals on emotionally different reinforcement was studied. 5-OTP (10 mg/kg) facilitated the training of rats on the food reinforcement, but aggravated it on the pain reinforcement. D, L-DOPA (20 mg/kg) facilitated the training on the food reinforcement. The influence of precursors on the peculiarity of the serotonin and noradrenaline distribution in the brain structures of trained animals was also determined by the biological significance of the reinforcement used in the training.
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PMID:[Characteristics of rat training on emotionally varied reinforcement under conditions of an oriented change in the level of brain serotonin and noradrenaline]. 30 22

1. A quantitative in vitro study has been made of the actions of glyceryl trinitrate and sodium nitrite on vascular smooth muscle (dog femoral artery and saphenous vein; rat portal vein); these have been compared with the actions of papaverine, isoprenaline, salbutamol, pentaerythritol tetranitrate and trimetazidine. 2. Glyceryl trinitrate was more active on the saphenous vein than on the femoral artery in inhibiting noradrenaline and potassium-induced tone. 3. Unlike glyceryl trinitrate, sodium nitrite and isoprenaline, papaverine and diazoxide inhibited noradrenaline-induced contractions of venous and arterial smooth muscle to the same extent. 4. The selective dilator effects of glyceryl trinitrate on venous smooth muscle may explain its action in alleviating the pain of angina pectoris. It is suggested that the use of these three vascular smooth muscle preparations (arterial, and veins with and without spontaneous myogenic activity) is a useful initial screening procedure for prospective antianginal drugs acting by venodilatation.
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PMID:Comparative effects of glyceryl trinitrate on venous and arterial smooth muscle in vitro; relevance to antianginal activity. 40 60


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