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 sensitivity and precision of rotation, prick and puncture methods of using the Duotip-Test for epicutaneous allergy skin testing were evaluated. Forty-one volunteers who had not taken any antihistamines within the previous two weeks were recruited. The mean age was 21.6 years (range 18 to 25 years). Histamine hydrochloride 1 mg/ml and 50% glycerol saline were used as positive and negative controls, respectively. Each method of testing was performed in triplicate on the volar surface of both forearms. Wheal and flare were measured 15 minutes later. Rotation, prick and puncture methods produced histamine mean wheal diameter +/- standard deviation of 6.61 +/- 0.87 mm, 3.86 +/- 1.03 mm, and 3.00 +/- 0.65 mm, respectively (p < 0.01). The coefficient of variation of rotation method was 13.13%. It was the only method that gave coefficient of variation lower than 20%. False negative and false positive proportions of rotation method using a 4 mm criterion for positive reaction were 1.5% and 0.75%, respectively. Rotation method was well accepted by the volunteers although it was ranked highest in pain. We concluded that the rotation method of using Duotip-Test is a highly reliable technique for skin testing.
 ...
PMID:Evaluation of three methods for using the Duotip-Test device for skin testing. 1127 Apr 70

Peripheral tissue injury and inflammation may result in a facilitated spinal nociceptive transmission and central sensitization. Particularly, nitric oxide (NO) and prostaglandins (PGs) have been shown to be key mediators involved in the induction and maintenance of this state. By means of spinal cord microdialysis we have determined interstitial glutamate, NO (NO2-/NO3-), PGE2, glycerol, glucose and lactate concentrations in the dorsal horns of the spinal cord following peripheral nociceptive stimulation to gain further insight into the link between excitatory neurotransmitters and metabolic functions in the spinal cord during nociception. Formalin and zymosan injection into one hind paw evoked a biphasic release of glutamate and NO with the glutamate peaks preceding those of NO. Moreover, zymosan induced a biphasic increase of interstitial glycerol concentrations accompanied by an increase of interstitial lactate indicating metabolic disturbances. In contrast, formalin injection led to an elevation of dialysate glucose concentrations which may be interpreted as an indication of enhanced metabolic activity. The sequential release of glutamate and NO in the dorsal horns of the spinal cord in response to peripheral nociceptive stimulation supports the theory that NO may act as a retrograde transmitter. The metabolic changes observed after formalin and zymosan injection suggest that an intense peripheral nociceptive stimulation may not only activate but also disturb metabolic activity and possibly membrane integrity in the spinal cord.
Pain 2001 May
PMID:Release of glutamate, nitric oxide and prostaglandin E2 and metabolic activity in the spinal cord of rats following peripheral nociceptive stimulation. 1132 42

Glycerol (an atoxic alcohol) and phenol (a toxic monohydroxybenzene) are currently used as neurolytic blocking agents to relieve pain or spasticity. In the present study we compared the endoneurial response of anhydrous glycerol and 7% phenol-aqua after intraneural injection into rat sciatic nerve, using electron microscopy and immunohistochemical stainings. Despite the wide use of these drugs, a systematic morphological study of their action has not been done. Electron microscope studies showed different patterns of nerve damage for glycerol and phenol. Glycerol injection resulted in gross sciatic nerve injury, with myelin fragments widely dispersed in the endoneurium 1-2 weeks after the injury. Phenol-aqua injection resulted in gross sciatic nerve injury with focal haemorrhagic necrosis; nerve fibres were segmentally dissolved 1-2 weeks after the injury. In both groups the first axonal sprouts appeared in the area of the lesion 2 weeks after the injury and the sprouts became myelinated in both groups by 4 weeks. Immunohistochemical staining showed that in the glycerol-treated nerves macrophages were widely scattered in the endoneurium by day 3; the number of macrophages proximal to the lesion site and at the lesion site was significantly higher in the glycerol-treated nerves than in the phenol-treated nerves both at days 3 and 7. In the phenol-treated nerves, macrophages appeared after 1 week and they exceeded the number of macrophages in the glycerol-treated nerves at 2 weeks. The number of Schwann cells remained low until 4 weeks in both groups. The results show that glycerol-induced nerve fibre damage with breaching of myelin fragments is followed by invasion of macrophages into the endoneurium after 3 days. The delayed invasion of macrophages after phenol injection may be due to occluded vessels or may be related to the denaturing effect of phenol on the proteins needed for macrophage attraction. Despite the rapid invasion of macrophages after glycerol injection axonal regeneration was delayed when compared to that seen after traumatic axotomy, but the axonal regeneration occurred at the same time in both experimental groups. Thus, the results suggest that after chemical axonotmesis the axonal regeneration rate is not dependent on the macrophage invasion rate alone and that other endoneurial changes also play a role.
 ...
PMID:Same axonal regeneration rate after different endoneurial response to intraneural glycerol and phenol injection. 1154 50

Trigeminal neuralgia is a disease affecting older individuals. The clinical hallmark of trigeminal neuralgia is a sudden, excruciating paroxysm of pain in the area of the trigeminal nerve. Drug therapy is considered the first line of treatment for trigeminal neuralgia. Anticonvulsant carbamazepine has been used. If relevant pharmacotherapy has been tried without any effect, other procedures are selected. These procedures are microvascular decompression(a radical technique), glycerol trigeminal rhizotomy, percutaneous trigeminal nerve decompression and nerve block. Nerve block with neurolytic solutions and radiofrequency thermocoagulation is a simple, less invasive therapy. In order to avoid hypesthesia and dysesthesia, nerve block using a high concentration of local anesthetics is recommended. In recent years, stereotactic radiosurgery for trigeminal neuralgia has emerged as a new therapeutic modality.
 ...
PMID:[Diagnosis and treatment of trigeminal neuralgia]. 1155 42

Splanchnic nerve fibers innervating the stomach were studied in anesthetized rats; 997 fibers in the T(9) or T(10) dorsal roots were identified by electrical stimulation of the splanchnic nerve. Thirty-one fibers responded to gastric distension. Extrapolated response thresholds ranged between 0 and 53 mmHg; seven fibers had thresholds for response > or =30 mmHg. Thermo- and/or chemosensitivity was tested in 18 of the 31 fibers. Four of twelve fibers responded to intragastric perfusion of heated saline; none of eight fibers tested responded to perfusion of cold saline. Infusion of glucose, L-arginine, or potassium oleate produced no change in resting activity. Intragastric instillation of 12% glycerol or an inflammatory soup (bradykinin 10(-5) M, PGE(2) 10(-5) M, serotonin 10(-5) M, histamine 10(-5) M, and KCl 10(-3) M) and prior heat stimulation sensitized responses to distension. The results reveal the presence of low- and high-threshold mechanosensitive fibers in the splanchnic innervation of the stomach. These fibers have the ability to sensitize, and they likely contribute to pain and altered sensations that can arise from the stomach.
 ...
PMID:Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. 1170 50

Trigeminal neuralgia solely involving the upper trigeminal nerve branch is rare. The SUNCT syndrome (short-lasting, unilateral, neuralgiform hemicrania with conjunctival injection and tearing) in which the periorbital pain lasts for 60-120 s, and is accompanied by conjunctival injection and tearing is even less common. Unlike trigeminal neuralgia, SUNCT is usually not relieved by medication. Three patients with SUNCT were treated with retrogasserian glycerol rhizolysis, two of them twice. All five treatments provided complete pain relief and the duration of the effects was 2 to more than 4 years. One of these three patients also had a third treatment with compression of retroganglionic fibres with a Fogarthy balloon, according to Mullan, of the upper trigeminal nerve with excellent results.
 ...
PMID:Neurosurgical treatment of short-lasting, unilateral, neuralgiform hemicrania with conjunctival injection and tearing. 1192 67

In this paper the treatment of patients with chronic, intractable trigeminal neuralgia by invasive electrical stimulation of the Gasserion ganglion is reviewed. Two different surgical techniques are employed in this treatment. Most frequently, a method similar to the traditional technique for percutaneous glycerol and radiofrequency trigeminal rhizolysis is used: a small percutaneous stimulation electrode is advanced under fluoroscopic control through a thin needle via the foramen ovale to the Gasserian cistern. Some neurosurgeons use an open surgical technique by which the Gasserian ganglion is approached subtemporally and extradurally, and the bipolar pad electrode is sutured to the dura. When percutaneous test stimulation is successful (at least 50% pain relief) the electrode is internalized and connected to a subcutaneous pulse generator or RF-receiver. Data from 8 clinical studies, including 267 patients have been reviewed. Of all 233 patients with medication-resistant atypical trigeminal neuralgia 48% had at least 50% long term pain relief. The result of test stimulation is a good predictor of the long term effect, because 83% of all patients with successful test stimulation had at least 50% long term relief, and 70% had at least 75% long term relief. Patients generally preferred this invasive method over TENS. The success rate in patients with postherpetic trigeminal neuralgia was very low (less than 10%). It is suggested that the likelihood of pain relief by electrical stimulation is inversely related to the degree of sensory loss. It is concluded that invasive stimulation of the Gasserian ganglion is a promising treatment modality for patients with chronic, intractable, atypical trigeminal neuralgia.
 ...
PMID:Electrical stimulation of the trigeminal tract in chronic, intractable facial neuralgia. 1193 64

There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.
 ...
PMID:Cannabinoid receptors and their ligands. 1205 30

Many aspects of the physiology and pharmacology of anandamide (arachidonoyl ethanol amide), the first endogenous cannabinoid ligand ("endocannabinoid") isolated from pig brain, have been studied since its discovery in 1992. Ethanol amides from other fatty acids have also been identified as endocannabinoids with similar in vivo and in vitro pharmacological properties. 2-Arachidonoyl glycerol and noladin ether (2-arachidonyl glyceryl ether), isolated in 1995 and 2001, respectively, so far, display pharmacological properties in the central nervous system, similar to those of anandamide. The endocannabinoids are widely distributed in brain, they are synthesized and released upon neuronal stimulation, undergo reuptake and are hydrolyzed intracellularly by fatty acid amide hydrolase (FAAH). For therapeutic purposes, inhibitors of FAAH may provide more specific cannabinoid activities than direct agonists, and several such molecules have already been developed. Pharmacological effects of the endocannabinoids are very similar, yet not identical, to those of the plant-derived and synthetic cannabinoid receptor ligands. In addition to pharmacokinetic explanations, direct or indirect interactions with other receptors have been considered to explain some of these differences, including activities at serotonin and GABA receptors. Binding affinities for other receptors such as the vanilloid receptor, have to be taken into account in order to fully understand endocannabinoid physiology. Moreover, possible interactions with receptors for the lysophosphatidic acids deserve attention in future studies. Endocannabinoids have been implicated in a variety of physiological functions. The areas of central activities include pain reduction, motor regulation, learning/memory, and reward. Finally, the role of the endocannabinoid system in appetite stimulation in the adult organism, and perhaps more importantly, its critical involvement in milk ingestion and survival of the newborn, may not only further our understanding of the physiology of food intake and growth, but may also find therapeutic applications in wasting disease and infant's "failure to thrive".
 ...
PMID:Endocannabinoids in the central nervous system--an overview. 1205 38

Acid-sensing ion channels (ASICs) are cationic channels activated by extracellular protons. They are expressed in central and sensory neurons where they are involved in neuromodulation and in pain perception. Recently, the PDZ domain-containing protein PICK1 (protein interacting with C-kinase) has been shown to interact with ASIC1a and ASIC2a, raising the possibility that protein kinase C (PKC) could regulate ASICs. We now show that the amplitude of the ASIC2a current, which was only modestly increased ( approximately +30%) by the PKC activator 1-oleyl-2-acetyl-sn-glycerol (OAG, 50 microm) in the absence of PICK1, was strongly potentiated ( approximately +300%) in the presence of PICK1. This PICK1-dependent regulatory effect was inhibited in the presence of a PKC inhibitory peptide and required the PDZ domain of PICK1 as well as the PDZ-binding domain of ASIC2a. We have also shown the direct PICK1-dependent phosphorylation of ASIC2a by [(32)P]phosphate labeling and immunoprecipitation and identified a major phosphorylation site, (39)TIR, on the N terminus part of ASIC2a. The OAG-induced increase in ASIC2a current amplitude did not involve any change in the unitary conductance of the ASIC2a channel, whether co-expressed with PICK1 or not. These data provide the first demonstration of a regulation of ASICs by protein kinase phosphorylation and its potentiation by the partner protein PICK1.
 ...
PMID:Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1. 1239 60


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