Complete Genome Sequences of Zika Virus Strains Isolated from the Blood of Patients in Thailand in 2014 and the Philippines in 2012.

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo sapiens-tc/THA/2014/SV0127-14 and Zika virus/H. sapiens-tc/PHL/2012/CPC-0740, isolated from the blood of patients collected in Thailand, 2014, and the Philippines, 2012, respectively. Sequencing and phylogenetic analysis showed that both strains belong to the Asian lineage.

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells.

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.

Quantifying altered long-term potentiation in the CA1 hippocampus.

Long-term potentiation (LTP) of synaptic transmission is a widely accepted model of learning and memory. In vitro brain slice techniques were used to investigate the effects of cortical-spreading depression and picrotoxin, an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, on the tetanus-induced long-term potentiation of field excitatory postsynaptic potentials. Cortical-spreading depression is involved in glutamate desensitization; on the other hand, GABA(A) antagonists could increase postsynaptic excitability. This study shows that picrotoxin effectively induced long-term potentiation with 142.25 ± 4.18% of the baseline in the picrotoxin group (n = 8) versus 134.36 ± 2.35% of the baseline in the control group (n = 10). In group with picrotoxin applied to CSD, we obtained the smallest magnitude of LTP (120.15 ± 3.73% of the baseline, n = 8). These results suggest that picrotoxin could increase hippocampal activity and LTP; on the contrary, CSD reduced LTP magnitude. In addition, the results also suggest that the decay rate of post-tetanic potentiation has a direct relationship with LTP. Moreover, data were interpreted by nonlinear least squares quantifying, and LTP could also be quantified. The nonlinear attribute of LTP had an influence on the fitting, with respect to increasing the accuracy of the parameters and the compatibility of combination of stimuli that produce LTP.

5-HT(1B/1D) serotonin receptor agonist attenuates nitroglycerin-evoked nitric oxide synthase expression in trigeminal pathway.

This study was conducted to investigate the effect of 5-HT(1B/1D) receptor activation on nitroglycerin (NTG)-induced cerebral hyperaemia and neuronal nitric oxide synthase (nNOS) expression in trigeminovascular neurones. NTG (10 mg/kg) was infused intravenously to adult male Wistar rats with or without pretreatment with 5-HT(1B/1D) receptor agonist, sumatriptan (0.4 mg/kg, intravenously). Cortical blood flow and expression of nNOS enzyme in trigeminal ganglia, trigeminal nucleus caudalis and perivascular nerve fibre surrounding superior sagittal sinus were measured. The results showed that pretreatment with sumatriptan could significantly shorten the period of NTG-induced cerebral hyperaemia without compromising the magnitude of hyperaemic peak. Sumatriptan pretreatment also attenuated the NTG-evoked expression of nNOS in all studied areas. Based on these findings, we suggest that 5-HT(1B/1D) receptor has an important role in stabilizing the trigeminovascular system by attenuating the expression of nNOS enzyme, hence reducing nitric oxide production.

Pathophysiology of chronic daily headache.

Despite no clear explanation of the mechanism underlying chronic daily headache, sensitization of central nociceptive neurons is one possibility. Either prolonged activation of peripheral nociceptors or any factors that can alter the endogenous pain control system can trigger this process. A decrease in platelet serotonin has been observed in patients with chronic tension-type headache as well as migraine patients with medication-induced headache. It was also shown that chronic analgesic exposure led to changes in the serotonin content and the density of the 5-HT(2A) receptor in the cerebral cortex. The plasticity of the serotonin-dependent pain control system may facilitate the process of sensitization and results in the development of chronic daily headache.

Visualization and characterization of respiratory syncytial virus F-specific CD8(+) T cells during experimental virus infection.

CTL play a major role in the clearance of respiratory syncytial virus (RSV) during experimental pulmonary infection. The fusion (F) glycoprotein of RSV is a protective Ag that elicits CTL and Ab response against RSV infection in BALB/c mice. We used the strategy of screening a panel of overlapping synthetic peptides corresponding to the RSV F protein and identified an immunodominant H-2K(d)-restricted epitope (F(85-93); KYKNAVTEL) recognized by CD8(+) T cells from BALB/c mice. We enumerated the F-specific CD8(+) T cell response in the lungs of infected mice by flow cytometry using tetramer staining and intracellular cytokine synthesis. During primary infection, F(85-93)-specific effector CD8(+) T cells constitute approximately 4.8% of pulmonary CD8(+) T cells at the peak of the primary response (day 8), whereas matrix 2-specific CD8(+) T cells constituted approximately 50% of the responding CD8(+) T cell population in the lungs. When RSV F-immune mice undergo a challenge RSV infection, the F-specific CD8(+) T cell response is accelerated and dominates, whereas the primary response to the matrix 2 epitope in the lungs is reduced by approximately 20-fold. In addition, we found that activated F-specific effector CD8(+) T cells isolated from the lungs of RSV-infected mice exhibited a lower than expected frequency of IFN-gamma-producing CD8(+) T cells and were significantly impaired in ex vivo cytolytic activity compared with competent F-specific effector CD8(+) T cells generated in vitro. The significance of these results for the regulation of the CD8(+) T cell response to RSV is discussed.

Effect of serotonin depletion on nitric oxide induced cerebrovascular nociceptive response.

The study was conducted to investigate the effect of serotonin depletion on nitric oxide-induced meningeal vascular response and cerebrovascular nociception. Nitroglycerin was infused i.v. to control and serotonin-depleted rats. Pial circulation was monitored by intravital fluorescent videomicroscopy and Fos immunoreactivity trigeminal nucleus caudalis neurons was used as an indicator for the cerebrovascular nociception. The results showed that the degree of nitric oxide-induced pial microvascular dilatation was significantly greater in the serotonin-depleted group than the control. The number of nitric oxide-evoked Fos-immunoreactive cells between the two groups remained comparable. The results suggest that though depletion of serotonin can facilitate the vascular response to nitric oxide it does not alter the nitric oxide-induced craniovascular nociceptive response.

Stress, anxiety and peripheral benzodiazepine receptor mRNA levels in human lymphocytes.

Peripheral benzodiazepine receptor (PBR) mRNA levels were measured in lymphocytes obtained from a cohort of university students and clinically diagnosed anxious patients. The average level of PBR mRNA was decreased in anxious patients compared to a control group. This data confirms previously published results, but it also indicates that PBR mRNA levels cannot be used as a sole diagnostic measure of anxiety because the range of the individual PBR mRNA levels of the anxious group overlapped the range of the PBR mRNA levels of the control group. PBR mRNA levels in students following academic examinations were increased in some individuals and decreased in others. In the same cohort of students individual levels of cortisol and prolactin were predominantly increased and decreased respectively. There was no correlation between the individual changes in the hormone levels or PBR mRNA, which suggests that each of these parameters is affected by different environmental and physiological factors. Lymphocyte PBR mRNA measurement is a useful additional methodology for studying human stress responses however, its use in clinical studies would require the elucidation of PBR's physiological role.

Platelet 5-HT(2A) receptors in schizophrenic patients with and without neuroleptic treatment.

It has been suggested that abnormal function of the serotonergic system may be implicated in the pathophysiology of schizophrenia. In order to examine the role of this system in schizophrenia, we have determined 5-HT(2A) receptors on human platelets of 20 control subjects and 37 schizophrenic patients by using [3H]spiperone and ketanserin. The data showed that the maximum number (B(max)) of 5-HT(2A) receptors for schizophrenic patients without neuroleptic therapy was significantly higher than that for control subjects. The B(max) values for [3H]spiperone binding to platelets of schizophrenic patients on butyrophenone, phenothiazine, benzisoxazole and thioxanthene therapies were significantly lower than those obtained from the drug-free group, but were comparable to control values. The effect of various medication periods on platelet 5-HT(2A) receptors was also examined. We found that after 2-4 weeks, 1-4 months, 4-12 months and more than 1 year of neuroleptic treatments, the B(max) values were significantly decreased when compared with values in the drug-free group. The present results indicate that treatment with various types of neuroleptics decreases the hypersensitivity of platelet 5-HT(2A) receptors. Significant clinical improvements occurred in all types of neuroleptic-treated groups and for all different treatment durations in this study. The precise mechanisms of how neuroleptics achieve their therapeutic effects still need to be further delineated.

Effect of chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache.

OBJECTIVE: To investigate the effects of chronic analgesic exposure on the central serotonin system and the relationship between the serotonin system and the analgesic efficacy of nonnarcotic analgesics. METHODS: Paracetamol was administered daily to adult male Wistar rats for a period of 15 or 30 days. Analgesic efficacy was measured by the tail flick test. After completion of the treatment protocol, the rats were humanely killed, and the frontal cortex and brain stem were isolated. Characteristics of the specific binding of the 5-HT2A serotonin receptor and the serotonin transporter were studied using a radioligand binding technique. Platelet serotonin was determined by high-performance liquid chromatography. RESULTS: Chronic paracetamol administration resulted in a significant decrease in the maximum number of 5-HT2A binding sites and an increase in the maximum number of 5-HT transporter binding sites in frontal cortical membrane (P<.001). Changes in the central 5-HT system were associated with a rise in platelet 5-HT levels. The degree of receptor downregulation, as well as transporter upregulation, became less evident after more prolonged drug administration. Readaptation of serotonin receptors and transporters coincided with the decrease in the analgesic efficacy of paracetamol, as well as a fall in platelet 5-HT levels. CONCLUSIONS: These findings provide further evidence in support of an involvement of the 5-HT system in the antinociceptive activity of simple nonnarcotic analgesics. Plasticity of this neurotransmitter system after chronic analgesic exposure may lead to the loss of analgesic efficacy and, in its more extreme form, may produce analgesic-related painful conditions, for example, analgesic abuse headache.

Hyposerotonin-induced nitric oxide supersensitivity in the cerebral microcirculation.

OBJECTIVE: To investigate the relationship between hyposerotonin and cranial microvascular responses to nitric oxide (NO). BACKGROUND: Although the mechanism underlying NO supersensitivity in migraine is still unclear, an alteration of the serotonin system is a possible explanation. METHODS: Wistar rats were divided into control and hyposerotonin groups. Serotonin was depleted by intraperitoneal injection with 300 mg/kg of para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor. Three days after PCPA pretreatment, the animals were prepared for assessment of their NO-induced vasomotor response using glyceryl trinitrate (GTN: 8 to 10 mg/kg, intravenously) as an NO donor. Pial circulation was visualized by the intravital fluorescein videomicroscopic technique. Images of vessels at 0, 5, 15, 30, and 60 minutes post GTN infusion were digitized and measured. At the end of monitoring, the rat brains were removed for ultrastructural study of the brain microvessels. RESULTS: Infusion of GTN produced dose-dependent pial arteriolar dilatation. This vasodilator effect was significantly increased in the PCPA-treated groups, especially at 30 and 60 minutes. The percentage change from baseline diameter at 30 minutes after the 8-mg/kg GTN infusion was 42.6 +/- 3.1 for the hyposerotonin group and 16.8 +/- 2.9 for the control group (P<.001). Electron microscopic study revealed that exposure to the NO donor produced considerable changes in cerebral microvessels, characterized by focal ballooning of endothelial cells, increased microvillous formation, and increased endothelial pinocytosis. These anatomical changes were significantly more prominent in the hyposerotonin group. CONCLUSIONS: A hyposerotoninergic condition can facilitate the NO-induced physiological and pathological responses in meningeal and cerebral microvessels and, therefore, is a possible explanation for the supersensitivity to NO observed in patients with migraine.

Induction of Th-1 and Th-2 responses by respiratory syncytial virus attachment glycoprotein is epitope and major histocompatibility complex independent.

In BALB/c mice, sensitization to respiratory syncytial virus (RSV) attachment (G) glycoprotein leads to the development of lung eosinophilia upon challenge infection with RSV, a pathology indicative of a strong in vivo induction of a Th-2-type response. In this study, we found that a strong, RSV G-specific, Th-1-type cytokine response occurred simultaneously with a Th-2-type response in G-primed mice after RSV challenge. Both Th-1 and Th-2 effector CD4(+) T cells recognized a single immunodominant site on this protein, implying that the differentiation of memory CD4(+) T cells along the Th-1 or Th-2 effector pathway was independent of the epitope specificity of the T cells. A similar observation was made in G-primed H-2(b) haplotype mice after RSV challenge, further suggesting that this process is not dependent on the peptide epitope presented. On the other hand, genes mapping to loci outside of the major histocompatibility complex region are crucial regulators of the development of a Th-2-type response and lung eosinophilia. The implication of these findings for the immune mechanisms underlying the pathogenesis of RSV is discussed.

Acetaminophen-induced antinociception via central 5-HT(2A) receptors.

Acetaminophen is one of the most widely used analgesic drugs. Although the mechanism of analgesic action of acetaminophen is still not known, the involvement of the central serotonin (5-hydroxytryptamine: 5-HT) system is one possibility. In the present study, we examined the antinociceptive effect of acute and chronic intraperitoneally (i.p.) administered acetaminophen by tail flick latency measurements in the rat. A significantly increased tail flick latency was observed in acute and 15-day acetaminophen-treated rats, but not in 30-day acetaminophen-treated rats, at a dose of 400 mg/kg/day. To investigate the plasticity of receptors at postsynaptic membrane, we conducted a series of experiments by radioligand binding method on frontal cortex and brainstem membrane. The technique involved radioligand binding with [phenyl-4-3H]spiperone and ketanserin for studying 5-HT(2A) receptor characteristics. A significant decrease in the maximum number of 5-HT(2A) binding sites (Bmax) was demonstrated in all treatment groups with acetaminophen 300 and 400 mg/kg on frontal cortex membrane, whereas the value of the dissociation equilibrium constant (Kd) remained unchanged. The down-regulation of 5-HT(2A) binding sites in frontal cortex was of a lesser magnitude after 30 days of treatment and the tail flick latency was as in the control animals. These results suggest that down-regulation of 5-HT(2A) receptor in response to 5-HT release is a major step in the mechanism underlying analgesia produced by this agent. On the contrary, chronic use of acetaminophen may result in 5-HT depletion, which in turn produces re-adaptation of postsynaptic 5-HT(2A) receptors. These data provide further evidence for a central 5-HT-dependent antinociceptive effect of acetaminophen.

Derangement of serotonin system in migrainous patients with analgesic abuse headache: clues from platelets.

Accumulating evidence indicates that serotonin (5-HT) may be involved in the process of analgesic-induced headache transformation. In order to clarify this hypothesis, we investigated the 5-HT system in migraine patients with analgesic abuse headache by using platelets as a neuronal model. Our results revealed a significant decrease in platelet 5-HT content in these patients compared to migraine patients and nonheadache controls (179.24 +/- 10.18, 451.22 +/- 14.35, and 480.22 +/- 13.98 ng/10(9) platelets, respectively; P < 0.001). This biochemical result was well correlated with a significant decrease (P < 0.001) in platelet dense body number observed in these patients (5.9 +/- 0.4 and 9.2 +/- 0.6 granules/10 platelets. For migraine patients with and without analgesic abuse headache, respectively). Beside the 5-HT depletion, the presence of numerous large intracytoplasmic vacuoles formed from the surface-connecting canaliculi system was found in this condition. Such a finding has not been previously described. The total area occupied by these vacuoles was significantly greater (P < 0.01) in migraine patients with analgesic overuse than in migraine patients and nonheadache controls (249.2 +/- 19.5, 164.1 +/- 19.5, and 183.1 +/- 20.3 nm2/cells, respectively). As this canaliculi system plays a significant role in the platelet secretory response, such dilatation may imply an excessive release of substances from this system. Based on this platelet model, we suggest that excessive use of analgesics alters the central 5-HT system by depleting 5-HT from its storage sites and results in the hyposerotonergic state. This analgesic-induced 5-HT alteration may be a possible mechanism of headache transformation observed in this condition.

Plasticity of 5-HT serotonin receptor in patients with analgesic-induced transformed migraine.

Chronic drug exposure can induce a significant change in neurotransmitter receptor systems and is possibly involved in the pathogenesis of drug-induced neurological disorders. Abuse of analgesics is known to induce deterioration in headache status in patients with primary headaches, especially migraine. To assess the possibility of 5-HT2A serotonin receptor plasticity in this condition, we investigated receptor binding on the platelet membrane in patients with analgesic-induced transformed migraine, patients with migraine, and nonheadache controls. Various concentrations of [3H]-spiperone (0.4 to 12 nmol) was used as a radioligand, and ketanserin was used to determine nonspecific binding. A lower maximal number of receptors (Bmax) was observed in patients with migraine as compared to patients with transformed migraine, and controls (467 +/- 58, 708 +/- 36, and 786 +/- 64 fmol/mg protein, respectively, P<0.01); whereas the value of the dissociation equilibrium constant (Kd) remained unchanged (1.72 +/- 0.16, 1.41 +/- 0.13, and 1.25 +/- 0.21 nmol for patients with migraine, patients with transformed migraine, and nonheadache controls, respectively). A significant decrease in Bmax value was observed in patients with transformed migraine after 4 weeks of analgesic withdrawal (770 +/- 25 and 345 +/- 31 fmol/mg protein, P<0.001), whilst no significant change in Kd value was observed (1.95 +/- 0.12 and 2.47 +/- 0.30 nmol, respectively). These findings indicate that 5-HT2A serotonin receptor system is altered in patients with transformed migraine with analgesic overuse. Such receptor plasticity may be an important step in the pathogenic mechanism of transformed migraine.

Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection.

T lymphocytes play a pivotal role in the immune response during viral infections. In a murine model of experimental respiratory syncytial virus (RSV) infection, mice sensitized to either of the two major glycoproteins of RSV develop distinct patterns of cytokine secretion and lung inflammation upon subsequent RSV infection. Mice sensitized to RSV-G (attachment) glycoprotein exhibit a strong interleukin (IL)-4 and IL-5 response and develop pulmonary eosinophilia, whereas mice sensitized to RSV-F (fusion) glycoprotein develop a predominantly T helper cell (Th)1 response and pulmonary inflammation characterized by mononuclear cell infiltration. In this study, we examined the potential role of virus-specific CD8+ T cytolytic T cells on the differentiation and activation of functionally distinct CD4+ T cells specific to these viral glycoproteins. Mice primed with recombinant vaccinia virus expressing RSV-F glycoprotein mounted a strong RSV-specific, MHC class I-restricted cytolytic response, whereas priming with recombinant vaccinia virus expressing RSV-G glycoprotein failed to elicit any detectable cytolytic response. Priming for a RSV-specific CD8+ T cell response, either with a recombinant vaccinia virus expressing RSV-G glycoprotein in which a strong CD8+ T cell epitope from RSV-M2 (matrix) protein has been inserted or with a combination of vaccinia virus expressing the matrix protein and the RSV-G glycoprotein, suppressed the eosinophil recruitment into the lungs of these mice upon subsequent challenge with RSV. This reduction in pulmonary eosinophilia correlated with the suppression of Th2 type cytokine production. The importance of CD8+ T cells in this process was further supported by the results in CD8+ T cell deficient, beta 2 microglobulin KO mice. In these mice, priming to RSV-F glycoprotein (which in normal mice primed for a strong cytolytic response and a pulmonary infiltrate consisting primarily of mononuclear cells on RSV challenge) resulted in the development of marked pulmonary eosinophilia that was not seen in mice with an intact CD8+ T cell compartment. These results indicate that CD8+ T cells may play an important role in the regulation of the differentiation and activation of Th2 CD4+ T cells as well as the recruitment of eosinophils into the lungs during RSV infection.

Prevalence and clinical features of chronic daily headache in a headache clinic.

Although chronic daily headache is regarded as a syndrome encountered in headache clinics, clinical characteristics have only rarely been studied and the condition has not been documented in Thailand. To investigate the prevalence as well as clinical features of chronic daily headache in Thai patients, 220 patients visiting Chulalongkorn Headache Clinic were examined. Sixty cases (27.3%) were diagnosed as suffering from chronic daily headache (male to female ratio, 1:5.7). The average age of these patients was 32.7 +/- 9.6 years. Based on the International Headache Society (IHS) criteria, 30% of patients with chronic daily headache could be diagnosed as suffering from migraine and 36.7% from chronic tension-type headache, whereas the remainder had combined features of both headache types and were not classifiable. Diffuse steady pain was the most common headache type reported (65%), however, associated features characteristic of migraine were often noted. These included photophobia (70%), phonophobia (56.7%) and nausea (43%). Thirty-four cases (56.7%) reported that their headache could be aggravated by stress. Daily use of analgesics was reported in 58.3% of cases. We concluded that chronic daily headache is a common problem. Although the mechanism has not been fully clarified, the prevalence of associated psychological factors and analgesic overuse imply their involvement in the pathogenesis of this condition. The criteria of the IHS are not entirely suitable for diagnosis and classification of this disorder, and modification of this classification system is needed.

Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection.

Mice sensitized to the G (attachment) or F (fusion) glycoproteins of respiratory syncytial virus (RSV) expressed different patterns of cytokine production and lung pathology when challenged by intranasal infection with RSV. Five days after challenge, mice sensitized to G glycoprotein produced high levels of interleukin-4 (IL-4) and IL-5 in the lungs and spleens and developed extensive pulmonary eosinophilia, while mice sensitized to F glycoprotein produced IL-2 and developed a mononuclear cell infiltration. Memory lymphocytes isolated 2 weeks after intranasal challenge of mice primed to the G or F glycoprotein secreted only IL-2 and gamma interferon (IFN-gamma) when stimulated with RSV. IL-4 and IL-5 production characteristic of Th2-type effectors in the lung was observed only after multiple rounds of in vitro stimulation of RSV G-specific memory T lymphocytes with antigen. Also IFN-gamma production appeared to play only a minor role in the expression of pulmonary pathology characteristic of Th1 or Th2 T-lymphocyte responses, because mice genetically deficient in IFN-gamma production by gene disruption displayed the same pattern of pulmonary inflammation to RSV infection after priming to RSV F or G as conventional mice. These results suggest that effector T lymphocytes exhibit a different pattern of cytokine production than memory T-lymphocyte precursors precommitted to a Th1 or Th2 pattern of differentiation. Furthermore, these observations raise the possibility that the cytokine response of human memory T lymphocytes after a single exposure to antigen in vitro may not accurately reflect the cytokine response of differentiated effector T lymphocytes at the site of infection in vivo.

Serotonin receptor adaptation in patients with analgesic-induced headache.

Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, alteration of serotonin receptor function is one possible mechanism. To assess the plasticity of 5HT2 serotonin receptors in this condition, we investigated receptor binding by the platelet membrane in patients with analgesic-induced headache (AIH), migraine and non-headache controls. The technique involved radioligand binding with (phenyl-4-3H)spiperone and ketanserin. A greater density of receptor numbers (Bmax) was found in patients with AIH and in non-headache controls (96.47 +/- 10.21 and 92.01 +/- 13.15 fmol/mg protein), as compared to migraine patients (49.52 +/- 5.14 fmol/mg protein). The value of dissociation equilibrium constant (KD) remained unchanged (3.07 +/- 0.49, 2.24 +/- 0.24 and 2.91 +/- 0.42 nM for patients with AIH, migraine and non-headache controls, respectively). Based on these findings, we suggest that up-regulation of 5HT2 serotonin receptors may be a possible mechanism of headache transformation in patients with AIH.

Platelet serotonin in patients with analgesic-induced headache.

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non-headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease (p < 0.001) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 +/- 30.7, 445.3 +/- 37.4 and 467.2 +/- 38.5 ng/10(9) platelets, respectively). In contrast, a difference of lesser statistical significance (p = 0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 +/- 195.1, 2610.0 +/- 173.1 and 2560 +/- 165.2 ng/10(9) platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as yet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.