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)

Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain tryptophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity.
 ...
PMID:Sympathetic control of tryptophan uptake and morphine analgesia in stressed rats. 242 29

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

Intravenous administration of acetyl salicylate of lysine, a soluble salt of aspirin, reduced in rats the firing discharge of thalamic neurones, evoked by noxious stimuli. Concomitantly, concentrations of 5-hydroxyindole acetic acid increased, while those of met-enkephalin-like immuno-reactive derivatives were decreased in several areas of the brain. Similar electrophysiological and biochemical responses were obtained by administering tryptophan or 5-hydroxytryptophan plus carbidopa. The effect of aspirin on the evoked firing of the thalamic neurones was counteracted by pretreating the animals with metergoline. On the other hand, naloxone did not antagonize the inhibitory effect of aspirin and 5-hydroxytryptophan on pain-induced neuronal excitation. These data indicate that a serotonin-, but not a naloxone-sensitive opiate mechanism, may be relevant for aspirin-mediated antinociception.
 ...
PMID:Effect of aspirin on serotonin and met-enkephalin in brain: correlation with the antinociceptive activity of the drug. 245 74

The 5-hydroxytryptamine (5HT) precursors tryptophan and 5-hydroxytryptophan had no significant effect on the behavior of rats in the formalin test when given by themselves. However, both compounds significantly attenuated the analgesic effect of morphine in the formalin test. The 5HT antagonist methysergide enhanced the antinociceptive effect of morphine but systemic 5HT had no effect. Assays of whole brain and spinal cord indoles revealed different patterns as a result of tryptophan or 5-hydroxytryptophan loading. The effect common to both treatments was an increase in brain 5HT. There was no effect of morphine on any measure. Formalin injection by itself did not alter indole levels in the brain or spinal cord. Our results, taken in conjunction with previous work, suggest that 1) 5HT in the spinal cord does not influence pain perception in the formalin test and 2) 5HT in the brain can antagonize morphine analgesia in the formalin test. We conclude that there may be circumstances in which the use of 5HT precursors for clinical pain management may be contraindicated.
 ...
PMID:Effect of 5-hydroxytryptamine precursors on morphine analgesia in the formalin test. 247 42

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

We have investigated the possible associations between the demographic, clinical and psychological characteristics of 80 patients with low back pain and the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal central nervous system metabolites of serotonin, dopamine and noradrenaline, and of tryptophan, the amino acid precursor of serotonin. Neither the clinical measures nor the psychological characteristics were significantly correlated with the CSF neurochemistry. Therefore the hypothesis about an intimate relationship between monoaminergic neurotransmission and the experience of chronic low back pain was not confirmed. Among the other factors studied, body height contributed most to the variance in both 5-HIAA and HVA concentrations; the levels of MHPG increased with age.
Pain 1985 Jan
PMID:Neurotransmission and the experience of low back pain; no association between CSF monoamine metabolites and pain. 258 Feb 62

Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.
 ...
PMID:Serum amino acids in fibrositis/fibromyalgia syndrome. 260 10

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment.
 ...
PMID:Amino acid levels in elderly nursing home residents. 263 18

1. Tryptophan increases 5HT synthesis, but the extent to which it increases 5HT release and therefore 5HT function is unclear. 2. The possibility that increased 5HT levels will lead to increased 5HT release is enhanced when 5HT neurons are firing at a higher rate. The rate of firing of 5HT neurons is increased as the level of behavioral arousal increases. Thus, altered tryptophan levels will be more likely to influence brain function at higher levels of arousal. 3. In the rat, tryptophan administration increased CSF 5HT appreciably when the animals were aroused by being put in the dark, but not when they were left in a lighted room. 4. In monkeys, the level of behavioral arousal does seem to influence the effect of altered tryptophan levels on aggression. This is consistent with the fact that altered tryptophan levels had no effect on aggression in normal subjects, but that tryptophan had a therapeutic effect in pathologically aggressive patients. 5. The confusing literature on the antidepressant effect of tryptophan can, to some extent, be explained by considering the circumstances in which tryptophan administration will lead to increases in 5HT release as well as increases in 5HT synthesis. 6. Although in some circumstances tryptophan can decrease pain perception by activation of spinal 5HT pathways, when it was given to postoperative patients it attenuated morphine analgesia by activation of a 5HT pathway in the brain. 7. The effect of altered tryptophan levels depend critically on the circumstances in which it is given.
 ...
PMID:Tryptophan availability, 5HT synthesis and 5HT function. 266 90

Effects of L-tryptophan supplementation and dietary manipulation were tested on patients with chronic myofascial pain around the temporomandibular joints. In this study, however, reduction of chronic pain reported in previous similar studies was not duplicated. No significant reduction in pain was noted in the groups receiving tryptophan and dietary manipulation compared with control groups.
 ...
PMID:The effect of L-tryptophan supplementation and dietary instruction on chronic myofascial pain. 273 42


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