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)

Pain was induced in 19 healthy individuals by double-blind injections into the temporal muscle of 0.2 ml of physiological saline with or without active substances added. 5-Hydroxytryptamine (2 nmol) caused pain similar to saline, bradykinin (2 nmol) only insignificantly more pain (0.05 less than p less than 0.1), while a mixture of the two substances in half dosage (1 nmol + 1 nmol) caused pain significantly above saline (p less than 0.01). Variations in the response to saline did not permit a conclusion to be made on the question of induced tenderness. However, the mixture of the two substances appeared to lower the pressure-pain threshold as measured by a pressure algometer (p less than 0.05).
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PMID:Pain and tenderness in human temporal muscle induced by bradykinin and 5-hydroxytryptamine. 208 37

Whole-blood serotonin (5-HT) and plasma norepinephrine (NE) were studied in 16 autistic children, 21 siblings of autistic children, and 53 parents of autistic children. Both plasma NE and whole-blood 5-HT were negatively correlated with vocabulary performance. Whole-blood 5-HT and plasma NE did not differ between autistic children with or without histories of self-injurious behavior or decreased pain sensitivity. Eighteen subjects were hyperserotonemic (whole-blood 5-HT greater than 270 ng/ml). For these subjects, plasma NE was significantly higher than for subjects without hyperserotonemia. Seven of 10 families with one hyperserotonemic member had two or more hyperserotonemic members. Observations of familiarity of whole-blood 5-HT suggest that larger-scale and more focused study of whole-blood 5-HT as a possible genetic marker may be productive.
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PMID:Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine levels and intelligence. 213 85

Behavioural and pharmacological evidence indicates that non-opioid analgesia in defeated male mice is initiated by anxiety and that serotongergic (5-HT) substrates are implicated. In the present study, the effects of the novel putative 5-HT3 anxiolytic, GR38032F, on this form of adaptive inhibition of pain have been examined. The results showed that defeat analgesia was totally inhibited by 1 microgram/kg-1 mg/kg of GR38032F, with partial inhibition evident over the dose range of 0.0001-0.1 microgram/kg and loss of efficacy at smaller doses. These highly potent effects of GR38032F are consistent with its anxiolytic profile in animal models and cannot be accounted for by indirect actions on basal nociception. These findings point to a potentially important modulatory role for 5-HT3 receptor mechanisms in defeat analgesia and, more generally, provide further evidence for the involvement of 5-HT in the mediation of non-opioid forms of environmentally-induced antinociception.
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PMID:Highly potent inhibitory effects of 5-HT3 receptor antagonist, GR38032F, on non-opioid defeat analgesia in male mice. 213 63

In a previous study, prolonged low-frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long-lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5-HT) systems were involved. More recently, we have shown that the 5-HT1 receptors are involved in the post-stimulatory decrease in blood pressure. In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 +/- 10% (P less than 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h. One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post-stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5-HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5-HT1&2 receptor antagonist) abolished the post-stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205-930 (5-HT2 and 5-HT3 blocking agents respectively). In another group of experiments, the serotonin receptor antagonists were administered post-stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors. 213 3

The 5-HT1A partial agonists, buspirone, ipsapirone and gepirone did not affect the latency to respond in the tail flick test to heat. However, they strongly attenuated the antinociceptive action of the mu-opioids, morphine and sufentanil. The buspirone metabolite, 1-(2-pyrimidyl)pyridine (1-PP) was ineffective. BMY 7378, spiperone and alprenolol, putative antagonists at 5-HT1A sites, did not modify basal latencies or the action of morphine. TFMPP and mCPP, agonists at 5-HT1B and 5-HT1C sites, also did not affect basal latencies or morphine induced antinociception. These data show that 5-HT1A partial agonists attenuate morphine-evoked antinociception without affecting basal thresholds. They represent an interesting aspect of the interaction between opioids and serotonin in the control of nociception. In addition to opioids (Millan, 1986), serotonin (5-HT) is considered to play a major role in the control of pain and in the expression of opioid analgesia (Roberts, 1984). The identification of a multiplicity of binding sites for 5-HT in the CNS (Fozard, 1987) raises the question of their individual roles in nociceptive processes. The 5-HT1A site is of particular interest since it is present in high concentrations in the dorsal horn of the spinal cord (Daval, Verge, Basbaum, Bourgoin, and Hamon, 1987) and there are conflicting reports that it may mediate analgesia or hyperalgesia (Berge, Fasmer, Ogren, and Hole, 1985, Zemlan, Kow, and Pfaff, 1983). Indeed, the 5-HT1A agonist, 8-OH-DPAT, was reported to attenuate morphine-evoked antinociception in mice (Berge et al., 1985).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Attenuation of opioid induced antinociception by 5-HT1A partial agonists in the rat. 213 88

This study investigated the effect of para-chlorophenylalanine (pCPA), on nicotine-induced analgesia. pCPA reduces physiological levels of 5-HT, a neurotransmitter that has been linked to pain. The effects of naloxone HCl and mecamylamine HCl on this analgesia were also assessed. Subjects were 24 albino rats. Each group of eight rats was injected subcutaneously (SC) with nicotine sulphate, followed by an intraperitoneal (IP) injection of one of the potential antagonists. Behavioral analgesia was assessed using the tail-flick test. Data analysis revealed that pCPA did not affect nicotine-induced analgesia. Consistent with past research, naloxone also had no effect, and mecamylamine effectively eliminated this analgesia. The results are interpreted in light of current knowledge of this behavioral analgesia and pain perception, in general.
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PMID:Effect of pCPA on nicotine-induced analgesia. 214 24

1. We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated extravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 micrograms kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P less than 0.005). 3. GR43175 (100 micrograms kg-1, i.v., rats; 30 micrograms kg-1, guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P less than 0.005, guinea-pig) or from 174 to 118% (P less than 0.05, rat) above vehicle-treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 mumol kg-1, i.v.). 4. GR43175 (30-300 micrograms kg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5. The protein leakage which followed the i.v. administration of 5-HT (1 mumol kg-1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg-1) and neurokinin A (1 nmol kg-1), was not blocked by GR43175 (100, 300 micrograms kg-1) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation. 6. GR43175 (100 micrograms kg-1) decreased bradykinin (10 mumol kg-1)-induced extravasation from 142 to 115% above vehicle-treated animals (P less than 0.05). 7. These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.
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PMID:The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. 215 35

The effects of ip intra-PAG injection of ACTH on serotonin (5-HT), norepinephrine (NE) contents of hippocampus and hypothalamus and pain threshold were investigated. The results showed: (1) After ip ACTH, the pain threshold, the contents of 5-HT of the two brain regions and the NE content of hippocampus were markedly elevated. Prior destruction of periaqueductal gray (PAG), the elevation of pain threshold and the increase of the 5-HT contents of two brain regions due to ip ACTH were completely abolished, while the effect of ACTH in elevating NE content of hippocampus still persisted. (2) After intra-PAG injection of ACTH, the pain threshold and the 5-HT contents in hippocampus and hypothalamus were significantly increased, however, the NE levels in hippocampus and hypothalamus showed no significant changes. The analgesic effect of the intra-PAG injection of ACTH was prevented by icv LSD, but not by naloxone, atropine, hexamethonium and phentolamine. (3) After icv ACTH, the pain threshold did not change. These results suggest that the serotoninergic system may be activated by PAG for mediation of ACTH-induced analgesia.
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PMID:[Serotonin of hippocampus and hypothalamus taking part in the analgesic effect of adrenocorticotropic hormone in rats]. 216 93

Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome. The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine. A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain. As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors. These receptors are present in certain intracranial blood vessels. 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters. Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain. Although these receptors are also found in certain blood vessels, they are present throughout the nervous system. The receptors appear to mediate neuronal depolarizations at the cellular level. Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems. Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine. These data offer a novel approach to the analysis of antimigraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine. Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome.
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PMID:Developments in 5-hydroxytryptamine receptor pharmacology in migraine. 225 14

The activity of 5-hydroxytryptamine (serotonin; 5-HT) in the central nervous system modulates sleep, the perception of pain and other functions of the body which might possibly relate to mechanisms of general anesthetic action. While administration of anesthetics has inconsistent effects on the content of 5-HT in brain, in vivo, accumulated data suggest that anesthetic drugs alter 5-HT homeostasis in the central nervous system. In an effort to identify one possible site of anesthetic action, the effect of halothane on the uptake of 5-HT was studied in synaptosomes isolated from the brain of rat. Established techniques were used to prepare the synaptosomal fractions and measure high affinity transport of radiolabelled 5-HT. Halothane inhibited synaptosomal accumulation of 5HT in a concentration-dependent manner, but had little effect on the passive or spontaneous release of the accumulated 5-HT. Rates of uptake of 5HT were inhibited by 43% in the presence of 1 mM halothane and by 75% of control in the presence of 5 mM halothane; the apparent I50 for halothane was 1.0 +/- 0.1 mM and Lineweaver-Burk analysis indicated the inhibition to be competitive at concentrations around the I50.
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PMID:Halothane inhibits 5-hydroxytryptamine uptake by synaptosomes from rat brain. 230 18


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