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)

Intracellular recordings were made from neurones in laminae I and II of the dorsal horn of a longitudinal, parasagittal spinal cord slice from the neonatal rat. Their responses to peripheral nerve stimulation were first tested. Then the responses to bath application of [Sar(9),Met(O(2))(11)]-substance P and [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin, neurokinin 1 (NK(1)) and mu-opioid receptor agonists respectively, were studied. Finally, the structure of each neurone was investigated by injecting neurobiotin intracellularly following recording, and immunocytochemical studies were performed on post-fixed tissues to reveal whether they expressed the NK(1) receptor. Nine lamina I neurones where shown to express NK(1) receptor and these were depolarised by [Sar(9),Met(O(2))(11)]-substance P. These neurones typically received a powerful C-fibre input that was strongly inhibited, presynaptically, by the mu-opioid receptor agonist.The structure, afferent input, opioid sensitivity and intrinsic properties of these neurones are all consistent with the view that they are a major relay for nociceptive information leading to intense pain. The characteristics of 10 other neurones studied in which the NK(1) receptor was not found to be expressed at levels detectable by immunocytochemistry are briefly described for comparison. These results contribute to the emergent view that the large neurones in the most dorsal neuronal layer (lamina I) of the spinal cord, which express the principal receptor for substance P (NK(1)) over their entire soma and dendrites, are a major relay for information leading to intense pain. Inhibition of the relay of information by these neurones would be predicted to result in analgesia and hence, a detailed knowledge of their unique neurochemical characteristics is of paramount importance.
 ...
PMID:Spinal lamina I neurones that express neurokinin 1 receptors: II. Electrophysiological characteristics, responses to primary afferent stimulation and effects of a selective mu-opioid receptor agonist. 1198 27

A 38-year-old woman with Chiari I malformation presented with spinal cord edema preceding syringomyelia manifesting as a 5-month history of nuchal pain and numbness of the upper extremities. Magnetic resonance imaging showed spinal cord edema, a poorly defined syrinx at the C-2 to T-2 levels, and distorted cerebellar tonsils. Computed tomography revealed cerebrospinal fluid (CSF) density in the center of spinal cord edema, and positron emission tomography revealed no uptake of L-[methyl-11C]methionine, indicating a non-neoplastic lesion. Craniocervical decompression achieved excellent clinical and neuroradiological outcomes. The success of surgical treatment supports the theory that patients with Chiari I malformation have increased transmural flow of CSF, causing spinal cord edema that progresses to syringomyelia. Early treatment of patients with spinal cord edema is indicated to prevent permanent spinal cord injury due to progressive syringomyelia.
 ...
PMID:Spinal cord edema preceding syringomyelia associated with Chiari I malformation--case report. 1237

Substance P (SP) acts as a transmitter of nociception in both the peripheral and the central nervous system. Because the NK-1 receptors in gerbils are comparable to those in humans, gerbil models could be used to study the role of SP in neuropathic pain. A modification of the rat chronic constriction injury (CCI) model of neuropathic pain was produced in male gerbils by placing four loose chromic catgut ligatures around the sciatic nerve. This procedure clearly resulted in mechanical hypersensitivity. Intraplantar injections of SP and the selective NK-1 receptor agonist, [Sar(9)-Met(O(2))(11)]-substance P (Sar-SP), to the paw ipsilateral to the nerve injury and intrathecal administration of these peptides produced paw-lifting behavior in the CCI gerbils in thermoneutral conditions. In sham-operated and nonoperated controls, no such effects were observed. Systemic administration of the NK-1 antagonist R116301 attenuated the SP and the Sar-SP-induced paw-lifting behavior in the CCI gerbils indicating the role of NK-1 receptors in these effects. Intraplantar injection of the highest dose of SP (200 ng) to the paw contralateral to the CCI produced lifting of the paw ipsilateral to the injury, indicative for spinal mechanisms especially since administration of SP to the ipsilateral front paw or even intracardially did not have any effect at all. The SP-induced responses were not antagonized by the NMDA antagonist MK801. These results indicate that the peripheral and spinal SP reveal an increased reactivity in a neuropathic pain model. This increased pain sensitivity seems to involve spinal NK-1 mechanisms.
 ...
PMID:Functional role of exogenous administration of substance P in chronic constriction injury model of neuropathic pain in gerbils. 1367 13

Paeoniflorin (PF) is an active glucoside in Shaoyao (peony root), and is transformed into an antispasmodic metabolite, paeonimetabolin-I (PM-I), by intestinal bacteria in the gut after oral administration of Shaoyao or Shaoyao-Gancao-tang (SGT, Shakuyaku-Kanzo-To in Japanese). SGT is a pain-relieving traditional Chinese formulation (Kampo-medicine in Japanese) and is often used together with antibacterial synthetic drugs, such as amoxicillin and metronidazole (AMPC-MET), in peptic ulcer therapy. Since the bioavailability of PF in SGT has been reported to be significantly reduced by co-administered antibacterial drugs, we investigated how to minimize this reducing effect of antibacterial treatment in the present study. We found that repetitive administration of SGT starting 24 h after AMPC-MET treatment rapidly restored the plasma PM-I concentration from SGT reduced by AMPC-MET, due to its restorative effect on the decreased PF-metabolizing activity of intestinal bacteria in rat feces. The present findings suggest that it may be clinically useful to administer SGT repetitively, starting 1 or 2 d after treatment with a mixture of AMPC-MET during their combination therapy, to accelerate the recovery of the reduced bioavailability of PF in SGT. Similar administration regimens may also be useful in other combination therapies involving traditional Chinese formulations and antibacterial synthetic drugs to ensure the efficacy of the bioactive glycosides in the formulations.
 ...
PMID:Restorative effect of repetitive administration of Shaoyao-Gancao-tang on bioavailability of paeoniflorin reduced by antibacterial synthetic drugs treatment in rats. 1460 Apr 6

In the spinal cord, nitric oxide (NO) pathway is involved in pain and hyperalgesia, and nitric oxide synthase (NOS) expression and NO production are upregulated following several noxious and lesion stimuli. However, the mechanism of the increases is yet not well understood. The present study was designed to address the question of whether substance P (SP) released in the spinal cord enhances NOS expression and NO production of the spinal cord in rats. [Sar(9), Met(O2)(11)]-substance P (Sar-SP), a neurokinin-1 (NK-1) receptor agonist, was administered by intrathecal injection via L(5)-L(6) intervertebral space to induce nociception. The pain threshold was determined by hot water induced tail flick test. NOS expression of the L(5) segment of the spinal cord was determined using NADPH-d histochemical staining. NO production of the lumbar enlargement of the spinal cord was determined by assaying NO3(-) and NO2(-), the end product of NO metabolism, using the method of aqua fortis reduction. We found that (1) intrathecal injection of Sar-SP (6.5 nmol) elicited a characteristic, caudally directed, nociceptive behavioural response consisting of intense biting, licking and scratching episodes. Tail flick test showed decrease in pain threshold. (2) following the behavioural responses, the NOS expression level, including the number and the staining density of the NADPH-d reactive cells, increased in the superficial portion of the dorsal horn (Laminae I-II) and the grey matter surrounding the central canal (LaminaX) of the L(5) segment of the spinal cord after the Sar-SP intrathecal injection. At the same time, NO production in the enlargement of the spinal cord increased. (3) The decreased pain threshold and the increases in NOS expression and NO production could be substantially inhibited by intrathecal injection of [[D-Arg(1), D-Trp(7,9), Leu(11)]-substance P] (spantide) (5 microg), a non-selective antagonist of NK-1 receptor, 5 min prior to the Sar-SP injection. It might be concluded that the release of SP resulted from nociceptive afferents increased NOS expression and NO production of the rat spinal cord.
 ...
PMID:[Intrathecal injection of Sar9, Met(O2)11-substance P, neurokinin-1 receptor agonist, increases nitric oxide synthase expression and nitric oxide production in the rat spinal cord]. 1469 85

Methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) (Met(8)) is known to act as a neurotransmitter or neuromodulator and it has been implicated in pain, cardiovascular and motor mechanisms, but its role in audition is currently unknown. In the present study we have applied an immunocytochemical technique and describe the distribution of cell bodies and fibers containing Met(8) in the auditory pathway of the rat. The main finding is that we found either Met(8)-immunoreactive fibers or cell bodies or both in virtually all nuclei of the rat auditory system except for the medial superior olive and the ventral division of the medial geniculate body in which we did not find any immunoreactivity for Met(8). This suggests that the neuropeptide Met(8) is widely distributed throughout the auditory system of the rat. Our results suggest that Met(8) could play at least two roles in hearing. It seems to be involved in the processing of the descending auditory pathway, and it may be implicated in the multisensory integration of auditory information that takes place in the non-lemniscal auditory pathway.
 ...
PMID:Immunocytochemical distribution of Met-enkephalin-Arg6-Gly7-Leu8 (Met-8) in the auditory system of the rat. 1469 92

Enkephalins are pentapeptides found in the human nervous system, where they are involved in the relief of pain. The interaction of these neuropeptides with the nerve cell membranes would be a key-step in the receptor binding. We have used both Fourier-transform infrared and solid-state NMR spectroscopies to shed light on the interactions responsible for the association of enkephalins with negatively charged membranes. More specifically, we have investigated the interaction of methionine-enkephalin (Menk) with DMPG and DMPS vesicles. Our results suggest that Menk interacts electrostatically with both model membranes via its terminal NH3+ group. However, the peptide induced the formation of elongated DMPG vesicles in the magnetic field. On the other hand, the association of Menk with DMPS bilayers was concentration-dependent and disrupted the membrane at high peptide concentrations. The different effect of methionine-enkephalin with the two types of anionic membranes is most likely related to the different fluidity of these systems.
 ...
PMID:Insights on the interaction of met-enkephalin with negatively charged membranes--an infrared and solid-state NMR spectroscopic study. 1472

Arginine has been used by millions of athletes over the past 20 years to enhance production of human growth hormone. The effects of arginine supplementation include increased fat burning and muscle building, enhanced immunity, and improvement in erectile function in men. Excessive doses of basic amino acids such as ethionine, methionine and lysine are known to damage the rat pancreas. Recent studies have demonstrated that excessive doses of arginine induce necrotizing pancreatitis in rats. In this article, we report a 16-year-old male patient hospitalized in our clinic because of severe pain in upper abdomen, nausea and vomiting who was suspected to have arginine-induced acute pancreatitis.
 ...
PMID:Acute pancreatitis possibly due to arginine use: a case report. 1526 24

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.
 ...
PMID:Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis. 1526 66

RFamide (RFa)-related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as 'anti-opioid'. They also decrease the rate of desensitization of acid-sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133-141]. We have tested the role of mollusc-derived peptide, FMRFa (Phe-Met-Arg-Phe-amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa-related peptides powerfully excite the majority of C-fibres in the skin-nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long-lasting discharges to the application of peptides (20 microm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185-1190]: the activation of C-fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C-fibres to RFa peptides, protons and amiloride: 74% of tested RFa-sensitive C-fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa-related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.
 ...
PMID:RFa-related peptides are algogenic: evidence in vitro and in vivo. 1534 14


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