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

Serotoninergic neuron is concerned as an one of the pivotal factor of the tissue inflammation which lead to pain behavior. Sarpogrelate HCl is a novel compound which may modulate inflammatory reaction through 5-HT2A receptor antagonist. We show the involvement of the 5-HT2A receptor activity in the inflammatory and neuropathic pain. Systemic or local sarpogrelate administration provokes antinociceptive effect on 5-HT- or formalin-produced inflammatory pain behaviour in relation to spinal glutamate. Local sarpogrelate inhibits apoptosis and neuronal degeneration after chronic construction injury(CCI). These effects are reversed by 5-HT2A receptor agonist. These results suggests sarpogrelate has a beneficial effect on hyperalgesia and neuropathic pain via inhibiting 5-HT2A receptor.
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PMID:[Involvement of peripheral 5-HT2A receptor activation in inflammatory pain]. 1155 35

Serotonin (5-HT) is a key neurotransmitter in the central nervous system. It is suggested that serotonergic dysfunction may be involved in the pathophysiology of fibromyalgia syndrome (FS). In this study, we aimed to investigate T102C polymorphism of the 5-HT2A receptor gene in FS. Fifty-eight patients with FS and 58 unrelated healthy volunteer controls were included in the study. In both groups, the C/C, C/T, and T/T genotypes of the 5-HT gene were represented in 31% (22.4% in controls), 50% (53.4%), and 19% (24.1%), respectively. The 5-HT2A receptor gene polymorphism results were not significantly different between patients and controls (chi squared test, P>0.05). There was a significant correlation between patients with the T/T genotype and the subgroup according to the SCL-90-R test, (analysis of variance, P<0.05). We also saw that patients with the T/T genotype had the lowest pain threshold. CONCLUSION. T102C polymorphism of the 5-HT2A receptor gene is not associated with the etiology of FS. Our results also indicate that the T/T genotype may be responsible for psychiatric symptoms of FS.
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PMID:Association of T102C polymorphism of the 5-HT2A receptor gene with psychiatric status in fibromyalgia syndrome. 1173 59

Certain features of chronic daily headache, namely, increased headache frequency, expansion of headache area, and cutaneous allodynia, may imply sensitization of central nociceptive neurons in the trigeminal pathway. Repetitive activation of the trigeminal nerve can lead to a biologic and functional change in trigeminal nucleus caudalis neurons, characterized by a decrease in nociceptive threshold and receptive field expansion. Suppression of the endogenous pain control system can facilitate the process of central sensitization. Evidence of such suppression in patients with chronic daily headache includes decreased platelet serotonin, up-regulation of 5-HT2A receptors, increased platelet nitric oxide production, and increased levels of substance P and nerve growth factor in the cerebrospinal fluid. Results from a number of animal experiments have indicated that chronic analgesic exposure leads to changes in serotonin content and density of 5-HT2A receptors in the central nervous system. This plasticity of the serotonin-dependent pain control system may accelerate the process of sensitization; a biologic outcome that is expressed clinically by the development of chronic daily headache associated with analgesic overuse.
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PMID:Chronic daily headache: a scientist's perspective. 1216 46

One of the major serotonin (5-HT) receptor subtypes expressed in the rat dorsal root ganglion (DRG) neurons is the 5-HT2A receptor. We have previously shown that 5-HT2A receptors in the peripheral sensory terminals are responsible for 5-HT-induced pain and hyperalgesia. In the present study, we characterized neurons expressing 5-HT2A receptors in the rat DRG neurons by means of in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and behavioral tests. In situ hybridization on consecutive sections revealed that 5-HT2A receptor mRNA is colocalized with calcitonin-gene related peptide (CGRP) mRNA (100/104; 96.2%) but not with c-Ret mRNA (1/115; 0.9%). Signals for 5-HT2A receptor mRNA were found in 9.4 +/- 2.2% of normal DRG (L5) neurons, most of which were small to medium in size. Four days of complete Freund's adjuvant-induced inflammation of the hindpaw doubled the incidence of 5-HT2A receptor mRNA-expressing neurons to 19.3 +/- 2.8%. The level of 5-HT2A receptor mRNA in DRGs of normal and various pathological conditions was then determined by RT-PCR. The level was up-regulated by peripheral inflammation, but not by axotomy or chronic constriction of the peripheral nerve. Systemic administration of 5-HT2A receptor antagonist (Sarpogrelate HCI) produced analgesic effects on thermal hyperalgesia caused by peripheral inflammation, but failed to attenuate thermal hyperalgesia in chronic constriction injury model. These findings suggest that 5-HT2A receptors are mainly expressed in CGRP-synthesizing small DRG neurons and may be involved in the potentiation of inflammatory pain in the periphery.
Pain 2002 Sep
PMID:5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats. 1223 91

Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. Rats were injected with capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal threshold measured before and after injection. The mechanical withdrawal threshold decreases 2 h after capsaicin injection. Two hours after capsaicin injection, the following drugs were administered intrathecally: bicuculline, blocks gamma-aminobutyric acid (GABAA) receptors; naloxone, blocks opioid receptors; yohimbine blocks, alpha2-adrenergic receptors; and methysergide, blocks 5-HT(1/2) receptors. In addition, NAN-190, ketanserin, and MDL-72222 were administered to selectively block 5-HT1A, 5-HT2A, and 5-HT3 receptors, respectively. Knee joint manipulation was performed 15 min after administration of drug. The knee joint was flexed and extended to end range of extension while the tibia was simultaneously translated in an anterior to posterior direction. The treatment group received three applications of manipulation, each 3 min in duration separated by 1 min of rest. Knee joint manipulation after capsaicin injection into the ankle joint significantly increases the mechanical withdrawal threshold for 45 min after treatment. Spinal blockade of 5-HT(1/2) receptors with methysergide prevented, while blockade of alpha2-adrenergic receptors attenuated, the manipulation-induced antihyperalgesia. NAN-190 also blocked manipulation-induced antihyperalgesia suggesting that effects of methysergide are mediated by 5-HT1A receptor blockade. However, spinal blockade of opioid or GABAA receptors had no effect on manipulation induced-antihyperalgesia. Thus, the antihyperalgesia produced by joint manipulation appears to involve descending inhibitory mechanisms that utilize serotonin and noradrenaline.
Pain 2003 Nov
PMID:Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord. 1458 Nov 23

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that occupies a uniquely important place in neurobiology because of its role in many physiologic processes such as sleep, appetite, thermoregulation, pain perception, hormone secretion, and sexual behavior. Serotonin dysfunction has been implicated in the pathogenesis of schizophrenia. Previous studies have shown an association between the T102C polymorphism of the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia. However, many negative findings have also been reported. We analyzed the T102C polymorphism of HTR2A of schizophrenic patients in two southern Chinese populations (n = 291) and matched controls (n = 307). No significant positive association was observed between either of the polymorphisms and all schizophrenics, nor was the polymorphisms and any population of schizophrenia. These data did not provide evidence for a contribution of the 102T/C SNP of HTR2A gene to susceptibility to the southern Han Chinese schizophrenia.
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PMID:102T/C SNP in the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia in two southern Han Chinese populations: lack of association. 1504 42

AT-1015 is a novel selective 5-HT2A serotonin receptor antagonist that is known to impair platelet aggregation and vasoconstriction. Serotonin has been hypothesized to contribute to claudication symptoms in individuals with peripheral arterial disease (PAD) via microvascular vasoconstrictor and thrombotic effects. AT-1015 was thus evaluated in 439 patients with claudication who were randomized in a double-blind, placebo-controlled trial comparing 10 mg, 20 mg, and 40 mg BID versus placebo for 24 weeks. Treadmill walking performance was assessed by peak walking time (PWT) and pain-free walking time (PFWT). Quality of life (QoL) was measured by the Walking Impairment Questionnaire (WIQ) and the Health Status Survey SF-36. Limb hemodynamics was assessed with the ankle-brachial index (ABI). The 40 mg arm was terminated prematurely by recommendation of the Data Safety Monitoring Committee due to an excess number of non-fatal myocardial infarctions. At study conclusion, there were no statistically significant differences in the mean change of PWT, PFWT, ABI and QoL between the 10 mg and 20 mg BID treatment groups compared with placebo. The proportion of patients who experienced an adverse event (AE) was similar across all treatment groups. Antimuscarinic and gastrointestinal AEs were more common in the AT-1015 treatment groups. Two deaths occurred: one in the placebo group and the other in the AT-1015 20 mg group. Although a prolongation of the QTc interval was observed in all groups, this was not clinically significant (QTc > 500 ms). Mean supine pulse rates were significantly increased in all AT-1015 treatment groups, consistent with predicted antimuscarinic effects. Population pharmacokinetic analysis fit a one-compartment model with first-order absorption and elimination. These data indicate that selective serotonin receptor blockade does not improve exercise tolerance or quality of life in individuals with claudication.
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PMID:Randomized trial of AT-1015 for treatment of intermittent claudication. A novel 5-hydroxytryptamine antagonist with no evidence of efficacy. 1523 Apr 84

The purpose of this article is to summarize recent findings on the role of serotonin in pain processing in the peripheral nervous system. Serotonin (5-hydroxtryptamine [5-HT]) is present in central and peripheral serotonergic neurons, it is released from platelets and mast cells after tissue injury, and it exerts algesic and analgesic effects depending on the site of action and the receptor subtype. After nerve injury, the 5-HT content in the lesioned nerve increases. 5-HT receptors of the 5-HT3 and 5-HT2A subtype are present on C-fibers. 5-HT, acting in combination with other inflammatory mediators, may ectopically excite and sensitize afferent nerve fibers, thus contributing to peripheral sensitization and hyperalgesia in inflammation and nerve injury.
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PMID:Serotonin in pain and analgesia: actions in the periphery. 1547 22

Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (<2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we examined maternal behavior for 3 days following CAR injection. Indeed, we observed a substantial increase in maternal attention to the pups at the time of inflammation, but this increase was not without its cost: a period of significant maternal neglect afterward.
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PMID:Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult. 1573 Aug 69

A young woman presented with multiple central hypersensitivity disorders, including fibromyalgia, headache, pelvic pain and several smooth muscle spasm disorders, including irritable bowel syndrome, irritable bladder and Raynaud's phenomenon. She also had significant fatigue and sleep problems. Her case illustrates the importance and surprising frequency of atypical bipolar mood disorders in people with multiple central hypersensitivity pain disorders, especially with depression and anxiety resistant to antidepressant treatment. Considering neurological mechanisms common to her overlapping disorders was very helpful in guiding treatment choices. This experience illustrates the value of serotonin receptor type 2 (5HT2) inhibition with atypical neuroleptics, of neural cation channel and glutamate inhibition with anticonvulsants, and the potential usefulness of antidepressants after establishing 5HT2 control to enhance downward inhibitory tracts. Medications with combined usefulness for both bipolar mood and pain disorders were highly effective for her multiple hypersensitivity problems.
J Pain Palliat Care Pharmacother 2004
PMID:Serotonin mechanisms in pain and functional syndromes: management implications in comorbid fibromyalgia, headache, and irritable bowl syndrome - case study and discussion. 1576 Aug 6


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