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 have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.
Pain 2001 May
PMID:The behavioural importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha. 1132 26

Pharmacological treatment for neuropathic pain, although often effective for brief periods, can result in intractable persistent pain with certain patients. Cell therapy for neuropathic pain is a newly developing technology useful for an examination of enhanced normal sensory function after nerve injury with the placement of cells near the spinal cord, and grafts of immortalized cells bioengineered to chronically supply the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been used to reverse the chronic pain behaviors. However, it is not known whether there is a therapeutic window for the use of intervention with cell therapy after partial nerve injury. To investigate whether neuropathic pain is sensitive to the timing of placement of cell grafts, neuronal cells bioengineered to synthesize GABA were transplanted in the lumbar subarachnoid space one to four weeks after unilateral chronic constriction injury (CCI) of the sciatic nerve and sensory behaviors were evaluated before and after CCI and transplants. Both thermal hyperalgesia and tactile allodynia were reversed when transplants were placed either one or two weeks after partial nerve injury, compared to maintenance of these behaviors with the injury alone. However, if GABA cells were placed any later than 2 weeks after nerve injury, such intervention was ineffective to reverse the thermal and tactile hypersensitivities induced by the injury. This suggests that altered spinal GABA levels may contribute to the early development of chronic neuropathic pain and that early intervention with cellular therapy to restore GABA may prevent the development of that pain.
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PMID:Only early intervention with gamma-aminobutyric acid cell therapy is able to reverse neuropathic pain after partial nerve injury. 1133 47

The present study assessed the efficacy and potency of intrathecal (i.t.) administration of the opiate morphine, the gamma-aminobutyric acid-B (GABA(B)) receptor agonist baclofen, the alpha2-adrenoceptor agonist clonidine and the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) on the acute allodynia-like behaviour after photochemically induced spinal cord injury (SCI) in rats. Rats displaying allodynia-like behaviours to brushing, von Frey hairs and cold stimulation 1-2 days after photochemically induced SCI were studied. In a cumulative dose regime, morphine (0.1-10 micrcog), baclofen (0.1-1 microg), clonidine (0.1-10 microg) and R-PIA (0.01-10 nmol) were administered i.t. through an implanted catheter at the lumbar spinal cord. All tested drugs dose-dependently reduced the brushing, von Frey hairs and cold stimulation-induced allodynia-like behaviour. No increase in adverse effects such as motor deficits was found for morphine, clonidine and R-PIA. There was a slight increase in motor impairments at the highest dose of baclofen. For the mechanical allodynia, morphine appeared to be most effective, whereas baclofen, clonidine and R-PIA only provided a partial alleviation. For the cold allodynia, morphine and baclofen were more effective than clonidine and R-PIA. In relieving acute mechanical and cold allodynia-like behaviours in rats 1-2 days after SCI, i.t. morphine and baclofen were superior to clonidine and R-PIA.
Eur J Pain 2001
PMID:Effects of intrathecal morphine, baclofen, clonidine and R-PIA on the acute allodynia-like behaviours after spinal cord ischaemia in rats. 1139 17

The dorsal horn of the spinal cord contains many transmitters and receptors involving in pain transmission and modulation. Monoamines and gamma-aminobutyric acid (GABA) play a key role in the modulation at level of dorsal horn (DH) of the spinal cord, the site of primary processing of afferent nociceptive information. Agents that enhance the action of GABA at the GABAA receptors can produce antinociception. For example intrathecal administration of benzodiazepines increases pain threshold in various models of pain. There is also substantial evidence for robust antinociceptive properties of spinal administration of clonidine and other alpha 2-agonists.
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PMID:[Role of the GABA-ergic and adrenergic system in transmission and modulation of pain and possibilities of pharmacologic control]. 1140 53

Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric acid. In preclinical models, it has shown activity as an analgesic agent. A randomized, double-blind, placebo-controlled, parallel-group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain model. Study medication was administered postoperatively to patients who had undergone elective surgery to remove one or two third molars, at least one of which was mandibular and fully or partially impacted in bone. The study was conducted in the UK at a single centre and evaluated pregabalin at doses of 50 and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity difference (PID), pain relief intensity difference (PRID), time to onset of analgesia, and duration of analgesia. The patient's global impression of the study medication was used as a secondary efficacy parameter. Efficacy data were evaluated for the intent-to-treat (ITT) population, defined as all randomized patients who took study medication. Results showed that there were statistically significant differences in PR, PID, and PRID between the 300-mg pregabalin group and placebo. In addition, the 300-mg pregabalin group had a significantly longer duration of analgesia than the ibuprofen group and had the highest score on the patient global impression of study medication. Adverse events were reported more frequently in the pregabalin 300-mg group. Pregabalin appears to have significant analgesic properties in the third molar extraction model. Further research is needed to confirm these findings.
Eur J Pain 2001
PMID:Pregabalin in patients with postoperative dental pain. 1146 77

In mammals, specific lipids and amino acids serve as crucial signaling molecules. In bacteria, conjugates of lipids and amino acids (referred to as lipoamino acids) have been identified and found to possess biological activity. Here, we report that mammals also produce lipoamino acids, specifically the arachidonyl amino acids. We show that the conjugate of arachidonic acid and glycine (N-arachidonylglycine (NAGly)) is present in bovine and rat brain as well as other tissues and that it suppresses tonic inflammatory pain. The biosynthesis of NAGly and its degradation by the enzyme fatty acid amide hydrolase can be observed in rat brain tissue. In addition to NAGly, bovine brain produces at least two other arachidonyl amino acids: N-arachidonyl gamma-aminobutyric acid (NAGABA) and N-arachidonylalanine. Like NAGly, NAGABA inhibits pain. These findings open the door to the identification of other members of this new class of biomolecules, which may be integral to pain regulation and a variety of functions in mammals.
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PMID:Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. 1151 19

The vast majority of people experience tension-type headache during their lifetimes. Boys experience tension-type headache slightly more than girls during preadolescent years. During adolescence and adult years, tension-type headache occurs more commonly in females. Tension-type headache changes in women occur in relation to gynecologic changes, including menses, pregnancy, and menopause. These changes are related to estrogen fluctuations. Estrogen fluctuations cause changes in neurochemicals important for pain signal transmission, including serotonin, gamma-aminobutyric acid, and enkephalins.
Curr Pain Headache Rep 2001 Oct
PMID:Estrogen and tension-type headache. 1156 Aug 10

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that is elevated in inflamed human dental pulp. Because GABA agonists are antihyperalgesic in other tissue, it is possible that GABA agonists have similar effects in dental pulp assuming that this tissue contains GABA receptors. We tested the hypothesis that dental pulp contains functional GABA(B) receptors using a GTPgamma35S binding assay. This is a functional assay because GTPgamma35S will be bound to cell membranes only when activation of metabotropic receptors has lead to binding and activation of their associated G(alpha)-proteins via release of GDP and binding of the GTPgamma35S. Baclofen, a GABA(B) agonist, evoked GTPgamma35S binding in both human and bovine dental pulp. This was mediated by the GABA(B) receptor because it was blocked by the selective antagonist phaclofen in both tissues. The presence of GABA and its receptor, GABA(B), suggests that this system may be relevant in the production or management of endodontic pain.
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PMID:Evaluation of functional GABA(B) receptors in dental pulp. 1159 91

Clinicians currently base decisions regarding the use of intrathecal drug therapy for chronic pain on reports from uncontrolled and retrospective studies that fail to rely on standardized outcome measures. In this article, we summarize what is known about currently administered intrathecal therapies, including opioids, gamma-aminobutyric acid agonists, alpha-2 adrenoreceptor agonists, local anesthetics (sodium channel antagonists), calcium channel antagonists, miscellaneous agents, and drug combination therapy. In addition, we offer a brief look at novel approaches that may revolutionize intrathecal drug delivery.
Curr Pain Headache Rep 2001 Dec
PMID:Spinal drug delivery. 1167 85

Oleamide is a recently described lipid, obtained from the cerebrospinal fluid of sleep-deprived cats. It has been observed that oleamide possesses several biological effects, such as sleep induction, and immunological suppression as well as serotonin and gamma-aminobutyric acid receptors activation. In addition, oleamide also binds to the cannabinoid receptors. In this study, we have observed that oleamide facilitates memory extinction in a passive avoidance paradigm, reduces core temperature and pain perception, but does not affect significantly locomotion. These results suggest that oleamide modulates memory processes. However, we do not know if oleamide impairs the retrieval of the memory associated to the "not go" behavior, or facilitates the fast re-learning of the "go" behavior. In addition, since these effects are also induced by marijuana and anandamide, it is very likely that oleamide may be affecting the cerebral cannabinoid system to induce its effects.
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PMID:Oleamide modulates memory in rats. 1168 40


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