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

We tested the hypothesis that neurochemical changes in the spinal cord dorsal horn associated with neuropathic pain states differ from those seen in association with non-painful neuropathies. Immunohistochemistry was performed on spinal cord sections from rats with a chronic constriction injury (CCI), which develop hyperalgesia, and from animals with a nerve crush injury, which do not develop hyperalgesia or other signs of a painful syndrome. Immunohistochemistry was quantified by computer-assisted densitometry. Calcitonin gene-related peptide (CGRP) immunoreactivity and substance P (SP) immunoreactivity were decreased from 1 to 4 weeks after injury in CCI and from 2 to 6 weeks in crush. Gamma-aminobutyric acid immunoreactivity was unchanged in both conditions at all time points. Met-enkephalin (Met-enk) immunoreactivity was increased in CCI and unchanged in crush. Although SP and CGRP are involved in pain transmission, we conclude that their decrease in immunoreactivity is not specific for the CCI model, but rather a more general event in nerve de- and regeneration. The increase in immunoreactivity for the opioid peptide Met-ink, however, was only seen in the late phase of CCI, and may be specific for conditions associated with neuropathic pain and its resolution.
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PMID:Neurotransmitters in the spinal cord dorsal horn in a model of painful neuropathy and in nerve crush. 856 Sep 81

Subcutaneous injection of diluted formalin (0.25 microliter of 0.5%) caused a biphasic pain response in mice. The first phase of pain was observed during the first 5 min., while the second phase occurred 10-30 min. after formalin administration. With the formalin test, it was found that the antinociception produced by the GABA-A antagonist, picrotoxin, and the GABA-B antagonist, phaclofen, was abolished when employed in combination. The opioid antagonist naloxone and antimuscarinic atropine also decreased the picrotoxin response. However, sulpiride, SCH 23390, phenoxybenzamine and propranolol did not alter the picrotoxin response. Administration of naloxone, sulpiride and propranolol showed a pain response. The data indicate that dopaminergic and adrenergic mechanisms may not be involved in the picrotoxin antinociceptive effect. However, postsynaptic GABA-A and GABA-B may be involved in the drug effect, and involvement of opioid or cholinergic systems can not be excluded.
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PMID:Effect of picrotoxin on antinociception in the formalin test. 873 66

Substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in saliva were measured in 55 patients with migraine during headache attacks (15 men and 40 women, average age 37.6 years), 36 patients with migraine in interictal periods (8 men and 28 women, average age 43.9 years), 48 patients with tension-type headache during headache attacks (18 men and 30 women, average age 47.3 years), and 25 patients with tension-type headache in interictal periods (10 men and 15 women, average age 48.6 years). Forty-three normal healthy volunteers composed the control group (17 men and 26 women, average age 32.7 years). Substance P levels in saliva were determined using competitive enzyme-linked immunosorbent assay, and were 26.9 +/- 45.1 pmol/mL in the patients with migraine during headache attacks, 30.0 +/- 59.7 pmol/mL in the patients with migraine in interictal periods, 243.5 +/- 1137 pmol/mL in the patients with tension-type headache during headache attacks, 101.3 +/- 364 pmol/mL in the patients with tension-type headache in interictal periods, and 21.2 +/- 17.4 pmol/mL in the healthy controls. 5-hydroxytryptamine levels in saliva were determined using reversed-phase high-performance liquid chromatography with electrochemical detection, and were 895 +/- 1075 ng/mL in the patients with migraine during headache attacks, 758 +/- 1375 ng/mL in the patients with migraine in interictal periods, 1646 +/- 1945 ng/mL in the patients with tension-type headache during active headache periods, 1167 +/- 1495 ng/mL in the patients with tension-type in headache-free periods, and 450 +/- 405 ng/mL in the healthy controls. Gamma-aminobutyric acid levels in saliva were determined using high-performance liquid chromatography with precolumn ortho-phthalaldehyde fluorescence detection. Gamma-aminobutyric acid levels in saliva were 36.8 +/- 49.8 pmol/mL in the patients with migraine during headache attacks, 17.9 +/- 25.2 pmol/mL in the patients with migraine in interictal periods, 16.0 +/- 18.3 pmol/mL in the patients with tension-type headache during active headache periods, 14.1 +/- 6.8 pmol/mL in the patients with tension-type headache in headache-free periods, and 21.6 +/- 22.7 pmol/mL in the healthy controls. The salivary substance P and 5-hydroxytryptamine levels in the patients with tension-type headache during active headache periods were significantly higher than those in healthy controls. In contrast, we found no significant differences between the salivary gamma-aminobutyric acid levels in the patients with tension-type headache and healthy controls. The high levels of salivary substance P and 5-hydroxytryptamine in tension-type headache patients during headache periods might reflect release of substance P from the pain sensory system. Saliva could represent a fluid particularly suitable to the study of neuropeptide release under specific conditions such as migraine and tension-type headache.
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PMID:Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in migraine and tension-type headache. 874 82

The purpose of this study was to verify the role of somatostatin (Som) of brain in analgesia of electroacupuncture (EA). Intracerebroventricular (icv) injection of Som caused a more marked elevation of pain threshold and of EA analgesic effect, but the activity of Ca(2+)-APTase in hippocampus was significantly decreased; The Som and GABA levels in hippocampus and brain stem were decreased by EA analgesia. The Som in hippocampus and brain stem were obviously depleted by icv injection of cycteamine, but without any change of pain threshold and analgesic effect of EA. These results indicated that the exogenous Som of brain potentiated the analgesic effect of EA, however, the decrease of endogenous of some brain regions took part in the process of EA analgesia.
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PMID:[Effect of brain somatostatin on electroacupuncture analgesia of rat]. 875 23

The results of stimulating human subjects with the LISS Cranial Stimulator (LCS) and the LISS Body Stimulator (LBS) include an increase or decrease in the activities of certain neurotransmitters and neurohormones and the reduction of associated pain, insomnia, depression, and spasticity. The effects were documented in human subjects with measurements of the serum concentration of the various agents and assessments of the symptoms being performed before and after stimulation. The stimulators had a carrier frequency of 15,000 hz, which utilizes the bulk capacitance of the body, and a 15 hz modulating bioactive frequency. The second modulating frequency presently used, 500 hz, reduces the energy input to the patient by half. Significant increases in levels of CSF serotonin and beta endorphin were recorded post stimulation. There were also elevations in the levels of plasma serotonin, beta endorphin, GABA and DHEA together with diminished levels of cortisol and tryptophan. Concomitant with these changes were significant improvements in the symptoms of pain, insomnia, spasticity, depression, and headache.
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PMID:Physiological and therapeutic effects of high frequency electrical pulses. 880 93

There is much evidence that tactile allodynia in rat models of mononeuropathy produced by sciatic nerve constriction is linked to disturbance of spinal GABAergic functions. Spinal cord stimulation (SCS) applied to such animals via chronically implanted electrodes may in some of the animals induce a significant increase of the withdrawal threshold in response to innocuous mechanical stimulation with von Frey filaments applied to the paw of the nerve ligated leg. The present study was performed in mononeuropathic animals with definite signs of tactile allodynia, which did not respond to SCS, GABA and the GABAB-agonist baclofen were administered intrathecally, in doses per se insufficient to influence the withdrawal thresholds, together with the previously ineffective SCS. This combination resulted in a marked and long-lasting increase of the thresholds. The GABAA-agonist muscimol given together with SCS also produced a similar, but less prominent threshold increase. The GABAB-antagonist 5-aminovaleric acid (5-AVA) produced a transient suppression of the threshold increase induced by SCS together with either GABA or baclofen. In contrast, the GABAA-antagonist bicuculline had no apparent inhibitory effect on the threshold augmentation produced by SCS combined with GABA or baclofen. It is concluded that SCS may operate by upgrading the spinal GABAergic systems and that its potential for producing pain relief is dependent upon the availability of responsive GABA-containing inhibitory interneurons. Moreover, it seems that the effects of SCS are more linked to the GABAB-than to the GABAA-receptor system.
Pain 1996 Aug
PMID:Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat. 888 Aug 52

Nociceptors belong to A delta and C afferents that are equipped in the periphery with receptors for detecting potentially damaging physical and chemical stimuli. This review summarizes experimental evidence that these receptors represented by ionic channels are also functionally expressed on the cell bodies of sensory neurones in short-term cultures. The nociceptors belong predominantly to the small and medium size DRG neurones in which algogens such as weak acids, capsaicin, bradykinin and scrotonin produce inward currents that can generate impulse activity. It seems likely that the neurones which are not sensitive to algogens but to GABA, ATP or glutamate, agents not producing pain in humans, belong to other categories of DRG neurones equipped for detecting other modalities of sensation. new techniques for physical stimulation of DRG neurones in culture may be of great help in the search for complementing the criteria for distinguishing nociceptors among other neurones in culture. It is suggested that such an in vitro model will be useful for studying cellular mechanisms of nociception.
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PMID:Can sensory neurones in culture serve as a model of nociception? 888 18

A heptadecapeptide (orphanin FQ or nociceptin) was recently identified as an endogenous ligand for the orphan opioid-like receptor. Here we report that intrathecal orphanin FQ produces dose-dependent depression of a spinal nociceptive flexor reflex in the rat. Furthermore, administration of orphanin FQ in rats with intrathecal catheters produced behavioural antinociception in the tail flick test with no signs of sedation or motor impairment. The reflex depressive effect of orphanin FQ was not reversed by antagonists of opioidergic, alpha 2-adrenergic and GABA-A receptors. Thus, orphanin FQ may suppress nociceptive input at the spinal level through an novel mechanism. Orphanin FQ or agonists of its receptor may represent novel analgesics for pain conditions which are not responsive to existing pharmacological therapy.
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PMID:Nociceptin or antinociceptin: potent spinal antinociceptive effect of orphanin FQ/nociceptin in the rat. 893 Sep 65

Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, II), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (> or = 10 mg/kg, IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100 mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect, thereby documenting the importance of GABAA receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABAA receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABAA receptor and its modulatory sites.
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PMID:Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain. 899 May 96

The syndrome of painful legs and moving toes is an uncommon and distressing condition with pain in the feet or legs and involuntary movements of the toes. It can follow spinal cord or cauda equina trauma, lumbar radiculopathy, injury to the feet, peripheral neuropathy or without any preceding causes. Ephaptic transmission in damaged nerve roots or peripheral nerves with central reorganisation may be the underlying mechanism of the syndrome. Treatment is difficult. We report a case of this syndrome following peripheral neuropathy, with a good early response to the GABA agonists baclofen and clonazepam. The role of different GABA agonists in the treatment of this condition needs to be better defined.
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PMID:The syndrome of painful legs and moving toes--a case report. 899 54


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