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

The influence of tonic serotonergic modulation on the responses of spinal dorsal horn neurons to natural peripheral stimulation was examined in physiologically intact, awake, drug-free cats. Systemically administered methysergide (maximum cumulative dose 2 mg/kg) caused significant changes in responses of some dorsal horn neurons to both mildly noxious and non-noxious stimulation. Individual changes provide evidence, in this model, for tonic 5-HT modulation of many aspects of sensory transmission at the level of the spinal cord. Taken together, the changes demonstrate the significant degree of plasticity that exists for some spinal dorsal horn neurons. It is clear that the plasticity of some spinal dorsal horn neurons allows for a much broader response profile than would be apparent under the restricted circumstances of a normal neurophysiologic study. Removal of tonic inhibition on responses to noxious stimuli may be an aspect of neuronal plasticity that functions to provide an immediate change in the way that the nervous system responds to a noxious stimulus.
Pain 1990 Feb
PMID:Tonic 5-HT modulation of spinal dorsal horn neuron activity evoked by both noxious and non-noxious stimuli: a source of neuronal plasticity. 230 66

Serotonin (5HT) binds in a saturable and specific manner to high affinity binding sites present on the surfaces of human lymphocytes and monocytes. We reported that migraine patients have an increase in 5HT binding parallel to the progression of the attack, with the appearance of a subsequent phenomenon of cellular deactivation. The same experiment previously carried out in cluster headache patients revealed a lack of high affinity binding sites, independently of the pain period. Low levels of plasma 5HT were recently described by Anthony in chronic tension-type headache. The implication of 5HT in tension headache was also hypothesized by Shukla with the demonstration of an increased 5HT uptake by platelets. We studied the 5HT binding on surfaces of lymphocytes and monocytes in 26 tension-type headache patients (16 affected by chronic form (CTH) of the disease and 10 by episodic form (ETH]. Fourteen clinically healthy subjects were used as controls. Circulating lymphocytes and monocytes were tested for their ability to specifically bind 5HT, using (3H) labeled 5HT. The "in vitro" 5HT binding curves to lymphocytes and monocytes of tension-type headache patients show a constant trend; during headaches, both CTH and ETH patients present a desensitization phenomenon with a complete loss of high affinity binding sites for 5HT. The 5HT binding curve observed in controls is indistinguishable from that of ETH patients studied outside the attack period. The total amount of 5HT bound appeared to be more markedly raised in CTH patients than in ETH patients when compared to control values.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impairment of 5HT binding to lymphocytes and monocytes from tension-type headache patients. 233 75

In lightly ananesthetised rats, electrical stimulation in the dorsal part of the periaqueductal grey matter (dPAG) produced an increase in the latency of the tail flick response accompanied by an increase in blood pressure and heart rate. Microinjection of 40-50nmol 5-HT bilaterally into the rostral part of nucleus paragigantocellularis lateralis (PGL) at the level of the facial nucleus attenuated the cardiovascular response to stimulation of the dPAG but had no effect on the analgesia. It is suggested that cardiovascular control neurones, but not the pain control neurones in the rostral part of PGL are subject to inhibitory serotonergic modulation.
 ...
PMID:Selective modulation of the cardiovascular response but not the antinociception evoked from the dorsal PAG, by 5-HT in the ventrolateral medulla. 235 38

This study surveyed the coexistence of serotonin-like immunoreactivity (5-HT-IR) with substance P-like immunoreactivity (SP-IR) in fibers and terminals within various portions of the spinal cord of the rat. A previously characterized technique of immunofluorescent double labeling was used to stain 5-HT-IR red and SP-IR green, and a search was then made for single fibers that fluoresced both colors. These were found to be most common in the ventral horn, wherein 99% of 5-HT-IR fibers were also immunoreactive for SP. Coexistence of these substances was very rare in the superficial dorsal horn: fewer than 3% of 5-HT-IR fibers were immunoreactive for SP. In the region surrounding the central canal and in the intermediolateral cell column (IML), over half of all 5-HT-IR fibers and terminals were doubly labeled. In the white matter, doubly labeled fibers were most common in the ventral funiculus and somewhat less common in the lateral funiculus. They were rare in the dorsal columns. It is concluded that the coexistence of 5-HT and SP in nerve fibers and terminals is associated with somatic and sympathetic autonomic motoneurons. The role of the coexistence of 5-HT and SP in somatosensation, including pain, is unclear.
 ...
PMID:The coexistence of serotonin- and substance P-like immunoreactivity in the spinal cord of the rat as shown by immunofluorescent double labeling. 244 Oct 7

Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may modulate the effects of 5-HT on postsynaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT on "pain behavior" remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected animals. Administration of the 5-HT agonists 5-methoxydimethyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine (0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes, as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes. 244 89

The involvement of endogenous serotonergic pathways in the mediation of antinociception has been indicated by electrophysiological, pharmacological and behavioral experiments. However, manipulation of the indole pathway, either by lesioning of raphe nuclei or drug intervention, often produces disparate results. In particular, serotonin (5-HT) synthesis inhibition with p-chlorophenylalanine (PCPA) has been reported to produce either hyperalgesia or analgesia, depending upon the type of pain measurement examined. In the present study, we sought to evaluate the effects of PCPA on (1) behavioral responses to noxious stimulation, and (2) levels of serotonin, tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in raphe nuclei (pallidus, obscurus, magnus and dorsalis) and spinal cord regions by HPLC with electrochemical detection. Treatment of rats with 400 or 600 mg/kg of PCPA for 3 consecutive days resulted in significant elevations in pain thresholds assessed by tail withdrawal from radiant heat as well as vocalization to electric shock of the tail. The effect of PCPA on vocalization threshold was particularly striking, for the majority of animals showed a nociceptive-specific attenuation of this response. Although the PCPA induced changes in indole content of the various raphe nuclei were not unequivocally dose-dependent, differential reductions of serotonin and 5-HIAA were clearly detected in the various raphe regions. Nuclei raphe pallidus and obscurus were depleted of 5-HT and 5-HIAA to the greatest extent, whereas levels detected in nuclei raphe magnus and dorsalis were reduced by 30-40% from control values. Metabolism of 5-HT and 5-HIAA appeared unaffected by PCPA in all regions examined except the dorsal portion of the spinal cord. These findings collectively suggest that the effects of PCPA are not uniform throughout the central nervous system and raise the possibility that discrepancies in the behavior literature may be attributed to drug-induced changes in some, but not all serotonergic pathways.
 ...
PMID:Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. I. Biochemical and behavioral analysis. 244 10

In the present study, the activation of the nociceptive dorsal horn neurons in rats by iontophoretic substance P (SP) has been observed. Thus, the role of SP in spinal nociception is further identified. In addition, the inhibitory effects of iontophoretic SP on nociceptive response (C response) of dorsal horn neurons can also be observed even in rats that have undergone dorsal half transection of spinal cord. These inhibitory effects can be partially blocked by pretreatment with iontophoretic bicuculline but not by naloxone. It indicates that the SP-induced inhibitory effects on the nociceptive response may be mainly mediated by the presynaptic inhibition in which gamma-aminobutyric acid (GABA) may be involved. In view of the fact that the inhibitory effect of stimulation of nucleus raphe magnus (NRM) on the nociceptive response of dorsal horn neurons in rats depleted of 5-HT with parachlorophenylalanine (pCPA) can be significantly blocked by iontophoretic SP-antagonist, it is supposed that SP may be involved in descending modulation on spinal pain transmission.
 ...
PMID:Dual action of substance P in nociception and pain modulation at spinal level. 245 Dec 86

The possible mechanism of electroacupuncture (EAc) in reference to the effects of neuropeptides on serotonergic neurons in rat spinal cord was studied. The tested drugs were administered by intrathecal injection or spinal push-pull perfusion. The results showed that baclofen, substance P (SP) and naloxone administered intrathecally could reduce the tail pressure pain threshold. The pain threshold was increased by met-enkephalin (EK) and EAc. The action of EAc was antagonized by naloxone. The release of 5-HT in the spinal cord evoked by tail pressure pain stimulation (TP) was inhibited by EK, baclofen and EAc. However, naloxone could potentiate the 5-HT release evoked by TP. EAc reversed the naloxone potentiation of TP-evoked 5-HT release. The 5-HT release evoked by exogenous SP, however, was potentiated by EK and EAc. From these results, it is suggested that the influence of EAc on 5-HT release may be due to activation of enkephalin-interneurons, which presynaptically inhibit the primary sensory neurons in the spinal cord.
 ...
PMID:Further evidence for possible analgesic mechanism of electroacupuncture: effects on neuropeptides and serotonergic neurons in rat spinal cord. 247 59

Serotonin levels in patients with trigeminal neuralgia were studied according to the pain syndrome. The results evidence normalization of the blood serotonin concentration, possibly due to a favourable effect of therapy on serotonin metabolism, which reflects activation and optimization of the gate system for pain control.
 ...
PMID:[The level of serotonin in the blood of patients with trigeminal neuralgia]. 248 Nov 1

The authors investigated the cerebral metabolism of tryptophan in patients suffering from malignant pain by means of CSF dosage of tryptophan (Trp), 5-hydroxytryptophan (5-HTP), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). The level of 5-HIAA in patients with pain was 66.48 +/- 13.67 ng/ml, while in those without pain was 25.05 +/- 13.25 ng/ml; the difference was statistically significant, p = 0.001. Trp, 5-HTP and 5-HT levels did not register significant differences in the two groups of patients, although a tendency to lower values was seen in patients with pain, supporting the hypothesis of increased turnover of this metabolic pathway in cancer patients. A statistically significant inverse correlation was also found between cerebral Trp levels and pain levels measured on the Scott-Huskisson visual analogue scale. The data obtained confirm the importance of the cerebral serotoninergic pathway in pain modulation and the interest which CSF analysis may have for the assessment of patients suffering from pain.
 ...
PMID:Cerebral tryptophan metabolism in humans in relation to malignant pain. 248 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>