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

Fibromyalgia syndrome [FM] has core clinical features of widespread pain and widespread abnormal tenderness. The specific cause of the altered neurophysiology that underpins these clinical manifestations remains unclear. However, increased sensitisation of neural networks that relates to pain, as well as interacting mechanoreceptors, appear important targets for modulation by pharmacological agents. Further, many FM patients have emotional distress and some are depressed. Antidepressant agents have therapeutic benefits in FM. If depression is present antidepressant drugs will provide typical benefits to mood but not always to other key outcome measures, such as pain or tenderness. Selective serotonin receptor reuptake blockers are not as effective for overall FM improvement as drugs that block both serotonin and norepinephrine in a relatively balanced way. Thus tricyclic antidepressants will improve many important FM outcomes but are effective in only about 40 percent of individuals. Newer agents of this class, such as duloxetine and milnacipran, show improvement in key FM outcomes in about 60 percent of patients. Longer term studies will indicate the durability of these responses and the overall tolerance of the drugs. Any drug therapy will need to be integrated with appropriate education, exercise and attention to psychological modulatory factors to achieve best results.
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PMID:Fibromyalgia syndrome: which antidepressant drug should we choose. 1645 18

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.
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PMID:The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize morphine-induced respiratory depression in humans. 1718

MD-354 (meta-chlorophenylguanidine) has been identified as a member of a novel class of 5-HT(3) serotonin receptor agonists. MD-354 is a 5-HT(3) receptor partial agonist that has been shown to behave as an agonist in some assays, and as an antagonist in others. MD-354 also binds at alpha-adrenoceptors (ARs) and displays an affinity for alpha(2B)-ARs comparable to its affinity for 5-HT(3) receptors. Although devoid of antinociceptive actions following systemic administration alone, MD-354 markedly enhances the antinociceptive actions of clonidine in the mouse tail-flick assay without potentiating the sedative side effects of clonidine. Although studies with MD-354 are still in progress, some pharmacological findings are described here. MD-354-related agents may represent drug adjuvants for the relief of severe pain.
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PMID:MD-354: what is it good for? 1746 87

Cytidine-5'-diphosphate choline (CDP-choline; citicoline) is an essential endogenous compound normally produced by the organism and is a source of cytidine and choline. Our recent studies on acute pain models demonstrate that intracerebroventricularly administered CDP-choline produces antinociception via supraspinal alpha-7 nicotinic acetylcholine receptors-mediated mechanism in rats. However, it remains to be elucidated which other supraspinal mechanisms are involved in the antinociceptive effect of CDP-choline. In this study, we investigated the role of the supraspinal opioidergic, GABAergic, alpha-adrenergic and serotonergic receptors in CDP-choline-induced antinociception. The antinociceptive effect of CDP-choline was evoked by the intracerebroventricular (i.c.v.) administration. Two different pain models were utilized: thermal paw withdrawal test and mechanical paw pressure test. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose-dependent antinociception. Non-specific opioid receptor antagonist naloxone (10 microg; i.c.v.) and GABA(B) receptor antagonist CGP-35348 (20 microg; i.c.v.) pretreatments inhibited the antinociceptive effects of CDP-choline (1.0 micromol; i.c.v.). In contrast, the alpha-1 adrenergic receptor antagonist prazosin (20 microg; i.c.v.), alpha-2 adrenergic receptor antagonist yohimbine (30 microg; i.c.v.) and non-specific serotonin receptor antagonist methysergide (20 microg; i.c.v.) pretreatments had no effect on CDP-choline-induced antinociception in the thermal paw withdrawal test and in the mechanical paw pressure test. Therefore, it can be postulated that i.c.v. administered CDP-choline exerts antinociceptive effect mediated by supraspinal opioid and GABA(B) receptors in acute pain models. Furthermore, supraspinal alpha-adrenergic and serotonergic receptors do not appear to be involved in the antinociceptive effect of CDP-choline.
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PMID:Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats. 1753 79

Microinjection of neurotensin (NT) into the rostral ventromedial medulla (RVM) produces dose-dependent antinociception. Here we show that antinociception produced by intra-RVM microinjection of neurotensin (NT) or the selective NT receptor subtype 1 (NTR1) agonist PD149163 can be partially blocked by intrathecal (i.t.) yohimbine, an alpha2-adrenoceptor antagonist and by methysergide, a serotonin receptor antagonist. Antinociception produced by the NTR2 agonist beta-lactotensin (beta-LT) is blocked by intrathecal (i.t.) yohimbine, but not by methysergide i.t. It is not known which noradrenergic cell group is involved in this newly identified noradrenergic component of NTR-mediated antinociception. These experiments provide the first evidence that selective activation of NTR2 in the RVM produces antinociception. These results also provide evidence that activation of NTR1 in the RVM produces antinociception through spinal release of norepinephrine (NE) and serotonin, and that activation of NTR2 in the RVM produces antinociception mediated by spinal release of NE.
Pain 2008 Apr
PMID:Neurotensin-produced antinociception in the rostral ventromedial medulla is partially mediated by spinal cord norepinephrine. 1766 42

Menstrual disorders affect millions of women in the United States and represent an important health burden. The most common menstrual disorders are dysmenorrhea and headache; these conditions are leading causes of work or school absenteeism and substantially impact quality of life. Headache associated with menses is often migraine and referred to as menstrual migraine. Although the pathogenesis of menstrual-related pain conditions is not fully understood, menstrual-related overproduction of prostaglandins is implicated in the pathophysiology of both menstrual migraine and dysmenorrhea. In clinical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line therapeutic option for managing pain associated with dysmenorrhea. NSAIDs also play a role in the acute treatment and intermittent prophylaxis of migraine. Triptans, a class of highly selective serotonin receptor agonists, represent the gold standard for acute treatment of migraine. In addition, hormone therapy is effective in many cases for treating dysmenorrhea and may be beneficial in the management of menstrual migraine. Thus, overlapping treatment regimens may be advantageous in treating the coexisting menstrual-related pain conditions of dysmenorrhea and migraine.
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PMID:Menstrual-related pain conditions: dysmenorrhea and migraine. 1853 89

Pulsed radiofrequency (PRF) has been reported to be effective in the treatment of several types of pain. The mechanism of action, however, is not well known. In a recent study, the antinociceptive effects of acute thermal pain were shown to be mediated via descending pain inhibitory pathways. In this study we observed an analgesic effect of PRF treatment in an adjuvant induced inflammatory pain model in rats. In this model, sciatic nerves were treated with PRF at 37 degrees and 42 degrees , which inhibited hyperalgesia in the inflammatory groups when compared to RF and sham treatment. This effect was attenuated after intrathecal administration of the alpha2-adrenoceptor antagonist yohimbine, the selective 5-HT3 serotonin receptor antagonist MDL72222, and the non-selective serotonin receptor antagonist methysergide. All three drugs were found to significantly inhibit the analgesic effect of PRF. The results suggest that the analgesic action of PRF involves the enhancement of noradrenergic and serotonergic descending pain inhibitory pathways.
Eur J Pain 2009 Mar
PMID:Mechanisms of analgesic action of pulsed radiofrequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. 1853 61

The serotonin receptor subtype 5 HT(1A) was one of the first serotonin receptor subtypes pharmacologically characterized. Over the last twenty years the 5 HT(1A) receptor has been the object of intense research efforts as witnessed by the 5 HT(1A) acting drugs marketed as anxiolytics. In recent years, several new chemical entities targeting the 5 HT(1A) receptor (alone or in combination with other molecular targets) have been proposed for novel therapeutic indications (neuroprotection, cognitive impairment, Parkinson Disease and related disorders, pain treatment). The present review will focus on those 5 HT(1A) receptor agents that entered preclinical trials starting from 2000.
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PMID:5-HT1A receptor, an old target for new therapeutic agents. 1869 Nov 30

Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT(1B/D/F)), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal "pain-sensory" fibers. However, as triptan receptors are also located on "pain-sensory" afferents throughout the body, it is surprising that triptans only reduce migraine pain in humans, and experimental cranial pain in animals. Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial, somatic and visceral pain in behavioral models in mice. Because sumatriptan must cross the blood brain barrier to reach somatic afferent terminals in the spinal cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless of route. However, in behavioral models of persistent inflammatory pain, we found a profound anti-hyperalgesic action of intrathecal, but not systemic, sumatriptan. By contrast, sumatriptan was completely ineffective in an experimental model of neuropathic pain. The pronounced activity of intrathecal sumatriptan against inflammatory pain in mice raises the possibility that there is a wider spectrum of therapeutic indications for triptans beyond headache.
Pain 2008 Oct 31
PMID:Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan. 1872 85

The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory refl exes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.
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PMID:Serotonin receptor modulators in the treatment of irritable bowel syndrome. 1872 19


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