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

.1 mol/L CaCl2 0.5 microliters, 0.06 mol/L ACh 0.5 microliters, 5.4 x 10(-3) mol/L gallamine triethiodide (cholinergic nicotinic receptor blocker) 0.5 microliter and 14.4 x 10(-3) mol/L atropine (cholinergic muscarinic receptor blocker) 0.5 microliter were injected through bilateral intracranial cannulae in rat habenula. Pain threshold was measured by the latency of tail-flick reflex elicited by radiant heat exposure before and after intracerebral injection. CaCl2 significantly reduced the basic pain threshold and weakened the effect of the acupuncture analgesia. ACh apparently antagonized the effect of acupuncture analgesia. Gallamine triethiodide could recover the pain threshold almost to the raised level by acupuncture, but atropine only strengthened the effect on pain threshold weakly and briefly. The results suggest that the antagonistic effect of Ca2+ may be mediated via ACh in habenula.
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PMID:[Antagonistic effect of electro-acupuncture analgesia with Ca2+ injection into habenula could be reversed by gallamine triethiodide]. 129 45

After rats received electroacupuncture (EA), leucine-enkephalin (LEK) content in striatum and dopamine (DA) concentration in both brain stem and diencephalon markedly increased, and noradrenaline (NA) level in telencephalon definitely decreased with an obvious elevation of pain threshold. However, a previous intraperitoneal injection of atropine, a blocker of muscarinic receptor, not only partially blocked the analgesic effect of EA, but also changed the effects of EA on LEK, NA and DA contents of the brain. The results indicate that cholinergic system plays an important role in electroacupuncture analgesia (EAA), which may be fulfilled partially through the central LEK and catecholamine (CA) systems.
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PMID:Effects of atropine on the changes of pain threshold and contents of leucine-enkephalin and catecholamines of the brain in rats induced by EA. 149 39

The present study examined the role of spinal cholinergic modulation of spinal mechanical and thermal transmission. Intrathecal administration of the cholinergic muscarinic receptor antagonists atropine or scopolamine in awake rats produced a dose-dependent decrease in the nociceptive mechanical withdrawal threshold of the rat tail. Pirenzepine, a selective muscarinic receptor type 1 antagonist, produced a similar effect at greater doses while mecamylamine, a nicotinic receptor antagonist, was without effect. The nociceptive tail flick (TF) reflex evoked by noxious heating was unaffected by the above drugs. Intrathecal administration of the cholinesterase inhibitor physostigmine produced a rapid, reversible and significant increase in the mechanical withdrawal threshold; TF latency was increased slightly but not significantly. Intrathecal administration of morphine, carbachol or clonidine all produced dose-dependent increases in TF latency; morphine and carbachol, but not clonidine, also increased the mechanical withdrawal threshold significantly. Intrathecal pretreatment with atropine reversed carbachol-produced increases in TF latency and the mechanical withdrawal threshold but did not affect increases in TF latency produced by intrathecal morphine or clonidine. The morphine-produced increase in the mechanical withdrawal threshold, however, was shifted rightward in a parallel fashion by intrathecal pretreatment with atropine. Intrathecal pretreatment with yohimbine did not affect the inhibitory effect of carbachol on either TF latency or the mechanical withdrawal threshold. These results suggest that a tonic, endogenous cholinergic muscarinic influence in the spinal cord, independent of spinal adrenergic mechanisms, modulates spinal mechanical transmission.
Pain 1991 Aug
PMID:Tonic cholinergic inhibition of spinal mechanical transmission. 166 Oct

In an earlier report from this laboratory, it was demonstrated that the central cholinergic system exerted a modulatory pro-inflammatory effect on carrageenin-induced paw inflammation in rats. In this study, the role of the central muscarinic receptors in cholinergic modulation of peripheral inflammation was investigated by using several M1 and M2 receptor agonists and antagonists. The M1 receptor agonists aceclidine and arecholine and the nonspecific muscarinic receptor agonist oxotremorine augmented carrageenin oedema, an effect attenuated by the M1 receptor antagonist scopolamine. Physostigmine behaved like a M1 receptor agonist at all dose levels. However, the other M2 receptor agonist, carbachol, produced a dose-dependent dual effect, with lower doses attenuating the oedema and higher doses augmenting the inflammation. While the former action appeared to be due to M2 receptor stimulation, because it was blocked by AF-DX 116--a M2 receptor antagonist, the latter action appeared to be induced by M1 receptor stimulation, because it was inhibited by scopolamine. The pro-inflammatory effect of the M2 receptor antagonists AF-DX 116 and gallamine appeared to be induced by enhanced neuronal release of acetylcholine, because the effects were not evident following pretreatment with hemicholinium, which attenuates synthesis of the amine. Muscarinic receptor binding studies with (3H)-QNB indicated that the corpus striatum has substantially higher population of M1 receptors compared with the cerebellum. In the corpus striatum, (3H)-QNB binding indicated initial up-regulation followed by down-regulation of M1 receptors during peak inflammation, which appeared to persist even after a decrease in the inflammation. In contrast, the M1 receptors in the cerebellum appeared to be down-regulated very transiently during the early phase of the inflammation. While these receptor alterations may be due to the inflammation, it is equally possible that they represent changes induced by the stress of pain and inflammation induced by carrageenin.
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PMID:Central muscarinic receptor subtypes and carrageenin-induced paw oedema in rats. 167 19

1. Co-localization of SP and CGRP was observed in a dense intraepithelial and perivascular network of capsaicin-sensitive sensory nerves in the nasal mucosa of different species, including man. The morphological similarity in the distribution of these nerves among various experimental animals and man indicates that animal experimental data may be used for the understanding of sensory mechanisms in the human nasal mucosa. 2. Release of CGRP into the venous effluent of the nasal mucosa in parallel with vasodilatation was demonstrated in vivo upon antidromic stimulation of the maxillary division of the trigeminal nerve or local i.a. capsaicin injection. 3. Infusion of capsaicin induced concentration-dependent increase in arterial, venous and superficial blood flow as well as V in the pig nasal mucosa. Exogenous SP, CGRP and VIP displayed concentration-dependent, but partly separate, vasodilatory profiles in the nasal mucosa. SP was more potent regarding maximal blood flow increase, whereas the vasodilatation induced by CGRP infusion was more long-lasting on an equimolar basis. Although VIP caused an increase in ABF and VBF as well as V, the LDF signal (i.e. superficial blood flow) was decreased, possibly due to a stealing phenomenon. 4. Local i.a. capsaicin infusion induced a bilateral chlorisondamine-sensitive atropine-resistant vasodilatation. However, i.a. capsaicin in higher doses also induced a chlorisondamine-resistant vasodilatation in the superficial vascular compartment of the nasal mucosa, presumably via the release of sensory neuropeptides. Thus, the vasodilatory effect of capsaicin may be due to a complex interaction of local effects on the sensory nerve terminals close to blood vessels in the nasal mucosa and a main parasympathetic central reflex. 5. Capsaicin, but not nicotine, induced a concentration dependent increase in irritation or pain upon local application to the human nasal mucosa. Since both agents evoked secretion, this indicates that capsaicin and nicotine activate different populations of sensory neurons. Local application onto the nasal mucosa of capsaicin and nicotine as well as metacholine induced a concentration dependent muscarinic antagonist sensitive increase in the secretory response. The capsaicin or nicotine-induced secretion was bilateral and could be markedly reduced by combined pretreatment with a local anaesthetic and a vasoconstrictor. Our findings suggest that the secretory effect of capsaicin and nicotine in the human nasal mucosa is mediated via a central parasympathetic reflex arc with a final muscarinic receptor mechanism. No clear-cut contribution seemed to be exerted by locally released tachykinins and CGRP as direct trigger substances for the secretory response to capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sensory and motor reflex control of nasal mucosal blood flow and secretion; clinical implications in non-allergic nasal hyperreactivity. 189 72

There is now substantial evidence that acetylcholinesterase inhibitors and muscarinic receptor agonists increase the pain threshold after both systemic and spinal administration. In rats, physostigmine gave a significant dose-dependent increase in latency times in the tail immersion test following intrathecal administration. The effect was antagonized with atropine. Neostigmine gave more prolonged latencies as did the muscarinic receptor agonist carbachol. Spinal cholinergic pathways for antinociception interacted with the spinal opioid and adrenergic nerve tracts. No cross-tolerance to the selective alpha 2-adrenoreceptor agonist guanfacine or to morphine was seen in rats tolerant of spinal carbachol antinociception. The mechanism of spinal cholinergic antinociception is not known but a muscarinic interneuron may explain the interactions with other neurotransmitters. Clinically, the centrally active cholinesterase inhibitor physostigmine has been shown to give postoperative pain relief although of short duration. Severe neurogenic pain has been successfully treated with physostigmine or distigmine.
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PMID:Cholinergic mechanisms in pain and analgesia. 269 28

1. Applications of capsaicin, nicotine and methacholine were made locally onto the nasal mucosa in human controls and patients suffering from hyperreactive nasal disorders. Perception of sensation was registered as a sympton score and secretion quantified. The sensory reaction (irritation - pain) to capsaicin was similar in the three groups studied, i.e. controls, a group of patients with the diagnosis of vasomotor rhinitis and a group of patients with increased nasal secretion as the main symptom of the hyperreactive disorder. Nicotine induced only a mild itching sensation in the three groups. However, capsaicin and nicotine challenge caused a significantly larger secretory response in the last group than in the unselected vasomotor rhinitis group and in the control group. 2. Pretreatment with muscarinic receptor antagonists almost completely abolished the secretory response to both capsaicin and nicotine, and blocked methacholine-induced secretion. Furthermore, pretreatment with a combination of local anaesthetic and vasoconstrictor agent abolished the capsaicin-induced irritation, as well as the capsaicin- and nicotine-induced secretion on both the ipsilateral and the contralateral side. Therefore, no clearcut contribution seems to be exerted by locally released peptides from sensory neurones as direct trigger substances for the secretory response to capsaicin. 3. In conclusion, the nasal secretory response, in man, to both capsaicin and nicotine, seems to be mediated via cholinergic parasympathetic reflexes. In patients with hyperreactive non-allergic disorders of the nasal mucosa with rhinorrhea as the main complaint, the enhanced secretion may be due to a hyperreactive efferent cholinergic mechanism rather than hypersensitive irritant receptors on capsaicin- and nicotine-sensitive sensory neurones. Challenge with irritant agents seems a useful test for the evaluation of both afferent and efferent reflexogenic responses in hyperreactive disorders of the nasal mucosa.
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PMID:Capsaicin and nicotine-sensitive afferent neurones and nasal secretion in healthy human volunteers and in patients with vasomotor rhinitis. 272 Feb 99

The antinociceptive effect of intrathecally administered carbachol at the L1/L2 level in the rat was evaluated using the tail immersion test. A dose dependent increase in the nociceptive reaction times was evident following intrathecal carbachol in the dose range of 2.5-15 micrograms. At doses of 20 micrograms and above, although still effective in the test, motor impairment was pronounced. The antinociception was antagonized with atropine, and with either pirenzepine (PZ) or AFDX 116, which are selective M1 and M2 muscarinic receptor blocking drugs, respectively. Spinal cholinergic pain modulation was also studied in rats pretreated with DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), which causes a selective depletion of the noradrenergic nerve fibres in the CNS. The increased latency times after spinal carbachol were attenuated in animals depleted of spinal noradrenaline by DSP4. In conclusion, spinal analgesia by carbachol in the rat may therefore be mediated through both M1 and M2 muscarinic receptor stimulation in the spinal cord. It is also concluded that this spinal cholinergic pain modulation is interacting with spinal noradrenergic nerve terminals, but that the mechanism of the interaction remains to be established.
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PMID:Characterization of the antinociception induced by intrathecally administered carbachol. 274 39

Conventional anticholinergics (better called muscarinic antagonists) do not differentiate between subtypes of muscarinic receptors and cause unpleasant side-effects in peptic ulcer treatment. Pirenzepine, the first M1-receptor antagonist, has more selective inhibitory properties on oxyntic gastric glands and accelerates healing rates in peptic ulcer. Pirenzepine and H2-receptor antagonists interact synergistically on parietal cell function; their combination seems to be of therapeutic advantage in defined indications. Telenzepine, a pirenzepine analogue with a modified tricycle and M1-receptor selectivity, is about 10 to 25 times more potent than pirenzepine in reducing basal and stimulated gastric acid secretion in man. In patients with duodenal ulcer 3 mg telenzepine nocte seems to be as effective as 50 mg pirenzepine twice daily in regard to ulcer healing and pain relief. Another pirenzepine analogue with a modified side-chain (AF-DX 116) proved to be cardioselective in animal pharmacology, and was characterized as an M2-receptor antagonist. This might be an important step for a more profound understanding of structure-activity relationships of muscarinic receptor antagonists.
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PMID:Present status and future perspectives of muscarinic receptor antagonists. 288 47

The present study describes developmental changes in autonomic controls of heart rate in a strain of rats genetically predisposed to hypertension (spontaneously hypertensive rats or SHR) and in a normotensive strain of rats (Wistar-Kyoto rats or WKY). Rat pups were tested at 4, 8, 12, and 16 days to determine heart rate changes after selective pharmacological treatments. Specifically, freely moving pups were treated with selective beta-adrenergic and muscarinic receptor blockers (i.e., atenolol and atropine methylnitrate), using procedures designed to produce minimal pain or discomfort. The results indicated that by 4 days of age there is a substantial sympathetic acceleratory influence on heart rate. Comparison of inferred autonomic control of the heart in prehypertensive SHR and normotensive WKY pups suggested exaggeration of this early sympathetic influence among SHR pups. After 2 wk of age, however, equivalent autonomic control of heart rate was seen in SHR and WKY rats, with the higher basal heart rate of SHR rats being mediated by an increased intrinsic heart rate (i.e., heart rate after combined blockade). These findings suggest that enhanced sympathetic nervous system activity may be an early expression of the genetic predisposition to develop hypertension.
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PMID:Development of autonomic control of heart rate in genetically hypertensive and normotensive rats. 614 73


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