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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally accepted that morphine exerts its analgesic effect by binding to specific opiate receptors in the brain and spinal cord. Since Hughes et al. isolated and identified two endogenous pentapeptides, Met- and Leu-enkephalin, from the brain and found that they acted as agonists at opiate receptors, alpha-, beta- and gamma-endorphins, larger peptides than enkephalins and having morphine-like activity, have been identified in either the brain or pituitary of various species. Several studies have demonstrated that enkephalins possess analgesic properties and that they are distributed in the pain-mediated pathways in the central nervous system. These findings suggest that enkephalins are important neurotransmitters or neuromodulators regulating pain transmission. We now report the isolation of a novel substance which has a Met-enkephalin releasing action. Our findings suggest the possibility of a regulating mechanism for the release of endogenous opioid peptides, especially Met-enkephalin.
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PMID:A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser. 22 2

The distribution of Met-enkephalin- and substance P-immunoreactive neurons was studied by indirect immunofluorescence in some areas related to pain and analgesia. Met-enkephalin- and substance P-positive cell bodies and nerve terminals were observed in the periaqueductal central gray, the nucleus raphe magnus, the marginal layers and substantia gelatinosa of the spinal trigeminal nucleus, and the dorsal horn of the spinal cord. Lesion experiments suggest that Met-enkephalin neurons in the dorsal horn and possibly in the spinal trigeminal nucleus are interneurons or propriospinal neurons with nerve terminals in the laminae I and II of the cord and in the superficial layers of the spinal trigeminal nucleus, respectively. These areas are also very rich in substance P-positive nerve terminals, mainly representing central branches of primary afferent neurons. The present immunohistochemical-anatomical findings support the hypothesis that stimulation-produced analgesia is related to activation of spinal and spinal trigeminal enkephalin interneurons forming axo-axonic synapses with (substance P?) pain afferents in the superficial laminae of the dorsal horn and the spinal trigeminal nucleus. These interneurons may be activated by sensory fibers and by descending fibers from medullary stimulation sites. Transmitter substances in these descending fibers may be 5-hydroxytryptamine and substance P.
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PMID:Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P. 33 26

Intramuscular hemangiomas are idiopathic lesions which are either tumoral or developmental in origin. A close association of abnormal blood vessels with nerve fibers is found and may suggest that nerves have a primary inciting role in the development of these lesions. In the current study, the number of nerve fibers in different zones around the tumors, as well as the type of neuropeptides present in these fibers, was quantitatively assessed by computer-assisted image analysis of immunohistochemical staining of histological slides. The number of nerve fibers as determined by positive staining by anti-protein S-100 antibodies was found to be elevated in the immediate vicinity of the abnormal blood vessels. The density of the nerve fibers rapidly declined with increasing distance from the hemangiomas, reaching normal values at distances of over 2 mm. Furthermore, hemangiomas contain a significantly higher number of calcitonin gene-related peptide (CGRP), substance P, and Met-enkephalin-positive fibers. The most significant rise in number is that of CGRP-positive fibers. This neuropeptide is a known mitogen, which could be responsible for the growth of the hemangiomatous blood vessels. Substance P is a nociceptive neurotransmitter and its presence can explain the pain which often accompanies even tiny intramuscular hemangiomas.
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PMID:Neuropeptidergic innervation of intramuscular hemangiomas. 137 96

The link between endogenous opioid peptides and the genetic predisposition to preferentially consume ethanol was examined in alcohol preferring C57BL/6J mice compared with the alcohol nonpreferring DBA/2 mice. Concentrations of Met-enkephalin pentapeptide or precursor in various brain regions of potential relevance were not different between the two strains. C57BL/6J mice had a significantly lower pain threshold that could be increased by a selective mu-receptor opioid agonist [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin. Treatment with this drug also decreased ethanol consumption in C57BL/6J mice. Increasing the synaptic half-life of endogenous enkephalins by the enkephalinase inhibitor kelatorphan also decreased ethanol consumption. Assay of endogenous enkephalin degrading activity showed increased enkephalinase activity in striatal issue of C57BL/6J compared with DBA/2 tissue. These results suggest that a relative lack of enkephalin peptides trans-synaptically, possibly resulting from enhanced enkephalin degradation may contribute to increase alcohol consumption in C57BL/6J mice.
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PMID:Endogenous opioids are involved in the genetically determined high preference for ethanol consumption. 165 11

The CSF levels of Met-enkephalin-Arg6-Phe7 and dynorphin A were measured in patients with fibromyalgia. The mean CSF Met-enkephalin-Arg6-Phe7 level was 35.1 +/- 2.4 fmol/ml (mean +/- S.E.M.). The mean CSF level of dynorphin A was 14.3 +/- 0.9 fmol/ml. Regression analysis showed a statistically significant correlation between Met-enkephalin-Arg6-Phe7 and dynorphin A (r = 0.5369, P = 0.001). When correlated to the previously measured CSF levels of beta-endorphin, a statistically significant correlation was found with Met-enkephalin-Arg6-Phe7 (r = 0.5055, P = 0.03) but not with dynorphin A (P greater than 0.05). The Met-enkephalin-Arg6-Phe7 and dynorphin A levels are elevated compared to the levels available for comparison groups. Therefore, a lack of endorphin secretion does not seem to be the basis for the hyperalgesia observed in these patients.
Pain 1991 Aug
PMID:No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7. 168 41

Substance P and somatostatin may be transmitters of nociceptive information, which are involved in the transmission of pressure and heat nociceptive information, respectively, in the spinal dorsal horn. Calcitonin gene-related peptide, which is present in the primary sensory neurons having substance P or somatostatin, may function as a pain-promoting substance and be involved in the production of inflammation-induced hyperalgesia. The descending noradrenergic system plays a role in inhibiting nociceptive transmission in the spinal dorsal horn, and inhibits the release of substance P evoked by noxious mechanical stimulation. Persistent noxious stimuli increase the release of Met-enkephalin from the nucleus reticularis gigantocellularis, which promotes the activity of the descending noradrenergic system. Morphine activates the descending noradrenergic system, acting on the nucleus reticularis gigantocellularis. Morphine also activates the descending serotonergic system, which inhibits the release of somatostatin evoked by thermal noxious stimulation.
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PMID:[Neuropeptide-mediated transmission of nociceptive information and its regulation. Novel mechanisms of analgesics]. 170 78

Although the analgesic effects observed during the application of vibration may be attributable to neuronal inhibition of the pain pathways, this does not account for the fact that pain relief sometimes persists for a long time after the end of vibration treatment. Two experiments were carried out in order to determine whether pain relief might involve the release of endogenous opioids. In the first experiment, we studied the effects of injecting either a morphine antagonist, naloxone (0.4 mg), or a placebo, on the analgesia resulting from vibratory stimulation in 12 patients suffering from acute or chronic pain. In the second experiment, the Met-enkephalin and beta-endorphin levels were determined before and after 30 min vibratory stimulation in the cerebrospinal fluid of 8 patients suffering from chronic pain and 1 control subject, all of whom had been fitted with a ventriculo-peritoneal drain which made it possible to collect samples of cerebrospinal fluid painlessly. The results of these experiments show, on the one hand, that the effects of naloxone on the vibration-induced analgesia did not differ from those of the placebo and, on the other hand, that no increase in the Met-enkephalin or beta-endorphin levels occurred concomitantly with pain relief. It will therefore be necessary to investigate other mechanisms as possible means of explaining the post-vibratory analgesic effects.
Pain 1992 Jan
PMID:Met-enkephalin and beta-endorphin are not involved in the analgesic action of transcutaneous vibratory stimulation. 173 78

In order to investigate the effects induced by acupuncture on the activity of enkephalinergic neurons in the spinal cord, either the lumbar or the cervico-trigeminal area was perfused with artificial cerebrospinal fluid (CSF) (0.1 ml/min) in halothane-anaesthetized rats, and Met-enkephalin-like material (MELM) was measured in 0.5 ml fractions of the perfusates. The effects of manual acupuncture performed by a traditional Chinese acupuncturist at the 'Zusanli' point on the right hind limb were compared to the effects induced by acupuncture applied at a non-acupoint next to 'Zusanli.' The manipulation of needles either at the 'Zusanli' point or at the non-acupoint had no effect on the release of MELM from the lumbar area but significantly increased the release from the cervico-trigeminal zone. It is concluded that manual acupuncture triggers a heterosegmental activation of enkephalinergic neurones within the spinal cord and that this effect is non-specific in terms of the location of the stimulated point.
Pain 1991 Oct
PMID:Acupuncture-like stimulation induces a heterosegmental release of Met-enkephalin-like material in the rat spinal cord. 177 Oct 94

Previous studies using the technique of microinjection into brain nuclei indicated that the periaqueductal gray (PAG), nucleus accumbens, habenula and amygdala play an essential role in pain modulation and that these nuclei possibly act through a 'mesolimbic neural loop' to exert an analgesic effect, in which Met-enkephalin (MEK) and beta-endorphin (beta-EP) have been implicated as the two major opioid peptides involved in antinociception. In the present study performed in rabbits, intracranial microinjection was supplemented with push-pull perfusion and radioimmunoassay to determine whether the release of enkephalins (ENK) and beta-EP was increased in these nuclei when the putative neural circuit was activated by morphine administered into one of the nuclei. The results showed: (1) microinjection of morphine into the PAG increased the release of ENK and beta-EP in the N. accumbens, and vice versa; (2) microinjection of morphine into the N. accumbens increased the release of ENK and beta-EP in the amygdala, and vice versa; (3) morphine microinjected into the PAG caused an increase in the release of ENK and beta-EP in the amygdala and vice versa, although the release of ENK in PAG was statistically not significant. These results indicate that PAG, N. accumbens and amygdala are connected in a network served by a positive feedback circuitry.
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PMID:Neurochemical studies on the mesolimbic circuitry of antinociception. 181 60

The possible influence of a noxious chemical stimulus on the activity of spinal enkephalinergic neurones was examined by measuring the outflow of Met-enkephalin-like material (MELM) in CSF perifusates from the lumbar and cervico-trigeminal zones in halothane-anaesthetized rats. Following subcutaneous injection of 50 microliters of a 10% formalin solution in saline into the muzzle, MELM outflow increased at the cervico-trigeminal level but not at the lumbar level. Conversely, a significant enhancement in MELM outflow occurred at the lumbar but not at the cervico-trigeminal level when formalin was injected into a hind paw. In both cases, the increase in MELM release took place 5-10 min after the treatment and was of short duration (5-10 min). It is concluded that noxious chemical stimuli can induce a transient activation of enkephalinergic neurones within spinal zones receiving the nociceptive inputs. The marked differences in the characteristics of spinal MELM overflow due to noxious chemical, thermal and mechanical stimuli further support the notion that each type of nociceptive stimulus probably activates spinal enkephalinergic systems by triggering distinct neuronal mechanisms.
Pain 1990 Jun
PMID:Subcutaneous formalin induces a segmental release of Met-enkephalin-like material from the rat spinal cord. 238 69


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