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

Previous findings in our laboratory have demonstrated that transplants of adrenal medullary tissue into the spinal subarachnoid space can alleviate pain, most likely via sustained local release of pain-reducing neuroactive substances from the transplanted chromaffin cells. The success of this work in animal models has led to preliminary clinical trials with promising results. However, before large-scale clinical studies are undertaken, numerous issues should be resolved, many of which can be readily addressed initially in the laboratory. One of these is the amount of donor adrenal medullary tissue necessary to produce long-term antinociception. Although tissue from two adrenal glands has generally been used, it is unknown whether less would be equally effective, or more could increase analgesic potency. To address this, various amounts of adrenal medullary tissue, ranging from one to ten donor glands, were used. Results showed lowered antinociceptive benefits when only one adrenal medulla was used, but only small and short-lived increases when donor material was increased substantially. In addition, assays of catecholamine and Met-enkephalin release in the host spinal CSF revealed only slight further increases following the transplantation of more than 2-4 glands. These results indicate that a small amount of adrenal medullary tissue is necessary and sufficient to produce sustained antinociception, and suggest that higher amounts may result in tolerance development or feedback inhibition. Another important issue is the ability to retain antinociceptive potency if donor tissue is maintained in culture prior to transplantation, since the coordination of donor harvesting and recipient availability is often difficult. To address this, donor adrenal medullary tissue was maintained in explant culture for various periods following dissection. Results indicated that adrenal medullary tissue can be maintained in culture for up to 30 days prior to transplantation without decrement in antinociceptive potency, and that a period of 7-21 days results in improved graft viability. Results of this study indicate that some of the critical issues for successful neural transplantation outcomes can be initially addressed in pre-clinical studies.
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PMID:Optimization of adrenal medullary allograft conditions for pain alleviation. 781 72

We investigated whether central pain mechanisms including the endogenous antinociceptive system are involved in functional abdominal pain--that is, abdominal pain without abnormal findings at routine examinations. beta-Endorphin, met-enkephalin immunoreactivity, and dynorphin immunoreactivity were measured in cerebrospinal fluid (CSF) from nine patients with long-lasting functional abdominal pain and nine pain-free controls undergoing minor surgery while under spinal analgesia. Furthermore, pain sensitivity was evaluated with an ischaemic pain test comparing 21 functional abdominal pain patients with two control groups: 1) 24 patients with organic abdominal pain due to duodenal ulcer, gallstone, or urinary tract calculi, and 2) 13 healthy pain-free controls. The CSF beta-endorphin concentration was significantly decreased in the functional abdominal pain group as compared with nine matched controls (P = 0.01). Met-enkephalin and dynorphin immunoreactivities were normal. This part of the investigation was suspended after nine patients had been tested, because of post-lumbar-puncture headache. With regard to pain sensitivity, no significant difference between the three groups was shown, but subdivision of the functional abdominal pain group showed that individuals with pain and no symptoms of irritable bowel syndrome (IBS) were significantly more sensitive to pain than functional abdominal pain patients with IBS and healthy controls (P = 0.04).
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PMID:Decreased cerebrospinal fluid beta-endorphin and increased pain sensitivity in patients with functional abdominal pain. 790 92

In laboratory animals and humans, pregnancy is associated with opioid-mediated elevations in the threshold for responsiveness to aversive stimuli. Previous pharmacological analysis has demonstrated that this analgesia results, at least in part, from the activation of spinal cord kappa opioid receptors utilizing dynorphin as the major opioid substrate. The present report demonstrates that during late pregnancy, the content of spinal dynorphin A(1-17 and 1-8) is altered in a region-specific fashion. As a result, levels of dynorphin peptides are elevated, but only in the lumbar spinal region. In parturient animals, lumbar levels of dynorphin A(1-8) remained elevated but there was an additional increment in the content of dynorphin A(1-17). During late gestation, spinal content of Met-enkephalin and its precursor are also elevated, but, in contrast to dynorphin peptides, there is no interaction between condition and spinal level. Possible analgesic synergy between mu-delta and kappa opioid receptor systems is discussed. It is concluded that some parameter(s) of the pregnant condition triggers the activation of a spinal cord dynorphin system that attenuates the pain associated with late pregnancy and labor.
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PMID:Spinal cord dynorphin: positive region-specific modulation during pregnancy and parturition. 810 19

One micrograms of tetracaine in the rat periaqueductal gray (PAG) produced a decline in baseline tail-flick latencies (hyperalgesia) from about 5 to 3.5 s over the course of 9 min, after which the latencies increased to about 4.5 s. One micrograms of Met-enkephalin in PGC caused an expected increase in latencies (analgesia) from about 4.25 to 6.2 s in 9 min, with recovery to 4.7 s after 15 min post-injection. Giving the preceding 2 nanoinjections simultaneously led to an essentially total block of the PGC analgesia. A control injection in PAG simultaneous with a Met-enkephalin injection in PGC did not block the latter's analgesic effect. Single control (artificial cerebrospinal fluid) injections in PAG or PGC were without effect. The hyperalgesic effect of PAG tetracaine supports the involvement of PAG in normally occurring, tonic descending pain inhibition. The block of PGC met-enkephalin analgesia by distant injection of tetracaine in PAG supports the necessity of PAG integrity for PGC analgesic function.
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PMID:Reversible tetracaine block of rat periaqueductal gray (PAG) decreases baseline tail-flick latency and prevents analgesic effects of met-enkephalin injections in nucleus paragigantocellularis (PGC). 846 89

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

Cerebrospinal fluid (CSF) concentration of Met-enkephalin immunoreactivity (Met-enkephalin-ir) was determined by radioimmunoassay in 47 patients with chronic tension-type headache and in 47 headache-free control subjects. Thirty-nine of the controls were patients receiving spinal analgesia before surgery for diseases not associated with pain; 8 were healthy paid volunteers. Patients reporting migraine more than 1 day per month were excluded. Pericranial tenderness, nociceptive flexion reflex and thermal pain thresholds were determined in the majority of the patients. The median level of CSF Met-enkephalin-ir was significantly higher (115 pmol/l) (quartiles (107-134) pmol/l) in the headache patients than in the controls (median 79 pmol/l) (quartiles (73-87) pmol/l) (Mann-Whitney, P < 0.001). No indication of sex-difference or correlation with age with respect to CSF Met-enkephalin-ir was found. No correlation was found between CSF Met-enkephalin-ir and either pericranial tenderness, nociceptive flexion-reflex threshold, or thermal pain threshold. There was no indication of correlation between consumption of mild analgesics and CSF Met-enkephalin-ir. The higher levels of CSF Met-enkephalin-ir in the headache patients may be indicate activation of the enkephalinergic antinociceptive system at the spinal/trigeminal level, whereas the beta-endorphinergic system appears normal. This enkephalinergic activation may be caused by increased activity in the primary nociceptive afferents, or may be compensatory to decreased activity in other endogenous antinociceptive systems than the opioid.
Pain 1995 Oct
PMID:Increased cerebrospinal fluid Met-enkephalin immunoreactivity in patients with chronic tension-type headache. 857 79

This study was designed to examine the role of endogenous opioid peptide mediation of elevated pain threshold in adult male Sprague-Dawley rats with long-term diabetes mellitus induced by streptozotocin (STZ). Diabetes resulted in a significant elevation in pain threshold as measured by the tail-flick and/or hotplate latency tests. The hypoalgesic response in diabetic rats to hotplate testing developed gradually over a 4-6 week period after a transient hyperalgesia during the first two weeks of diabetes. The elevation of pain threshold achieved peak level by the fourth week after STZ administration, and remained at that level throughout the experimental period (up to 13 weeks). This hypoalgesic state in diabetic animals is thought to be mediated by opioid receptors (i.e. mu and delta). The involvement of the mu receptor is supported by the effect of naltrexone on the STZ-diabetic rats; naltrexone significantly attenuated the increase in tail-flick and hotplate latencies, compared to that of the non-diabetic controls. Furthermore, the concentration of native (free) Met-enkephalin in the spinal cord of STZ-diabetic rats was about 5-fold higher than that of non-diabetic animals. Such high levels of Met-enkephalin suggest the involvement of delta opioid receptors in the hypoalgesic response observed in STZ-diabetic rats. Seven weeks of insulin treatment, initiated after development of the hypoalgesic response, normalized not only plasma glucose level and body weight of diabetic rats, but also returned their antinociceptive latency toward normal. The results of this study showed that long-term diabetes is associated with altered pain threshold and further support the hypothesis for endogenous opioid peptide mediation of hypoalgesia in chronically diabetic rats that can be prevented by insulin treatment.
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PMID:Endogenous opioid peptide mediation of hypoalgesic response in long-term diabetic rats. 891 59

Previous studies in our laboratory have shown that estradiol and progesterone affect beta-endorphin and Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. The present investigation was conducted to evaluate the effects of estradiol and progesterone on pain latency and brain opioid receptors of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12 hr light:12 hr dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 micrograms/kg/day in 0.2 ml olive oil) and progesterone (5 mg/kg/day in 0.1 ml olive oil) were administrated subcutaneously in the dorsal neck region alone and in combination at 16:00 hr for 7 days. Control animals received 0.2 ml olive oil. Control and treated groups were evaluated daily for pain latency postinjection using the tailflick and hotplate methods. On Day 7 of drug treatment, animals were sacrificed by decapitiation after pain latency evaluations. Whole brains were removed and immediately frozen at -70 degrees C. Binding and affinity of brain opiate receptors were determined for each treatment group. Results obtained indicate that estradiol and progesterone treatment alone or in combination significantly alter pain latency. This alteration in pain was not accompanied by any change in affinity or number of mu opioid receptors. However, an increase in Kd of kappa opiate receptors was observed following treatment with estradiol, progesterone, or their combination. This increase in Kd of kappa opiate receptors may in part explain the increased hotplate sensitivity following estrogen administration. The present findings suggest that the decrease in pain sensitivity induced by estradiol or progesterone could not be explained by their effects on opioid receptors. The previously reported effects of estradiol and progesterone on brain levels of beta-endorphin and Met-enkephalin may contribute to the analgesic effects of these steroids.
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PMID:The effects of estradiol and progesterone on pain sensitivity and brain opioid receptors in ovariectomized rats. 891 80

Recombinant herpes simplex virus-1 encoding the rat preproenkephalin A (HSVLatEnk1) was generated for driving the expression of preproenkephalin A-derived peptides in dorsal root ganglia of rats in vivo. Three weeks after infection via the hind footpads, quantitative RT-PCR and in situ hybridization experiments showed a strong expression of preproenkephalin A mRNA in lumbar dorsal root ganglia. In addition, a 40-160% increase in radioimmunoassayable Met-enkephalin-like material concentrations was found in the dorsal spinal cord and dorsal root ganglia, respectively, at the lumbar level in HSVLatEnk1-infected rats as compared with animals infected with beta-galactosidase-encoding recombinant herpes simplex virus-1 or control rats. These data demonstrate the efficacy of the preproenkephalin A encoding vector and suggest that it should help in elucidating the role of Met-enkephalin-containing primary afferent fibers in pain transmission and/or control.
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PMID:Herpes simplex virus 1-mediated transfer of preproenkephalin A in rat dorsal root ganglia. 948 53

Recently, mu-, delta- and kappa-opioid receptors have been cloned and relatively well-characterized. In addition to three major opioid receptor types, more extensive studies have suggested the possible existence of other opioid receptor types that can be classified as non-mu, non-delta and non-kappa. Based upon anatomical and binding studies in the brain, the sensitive site for an endogenous opioid peptide, beta-endorphin, has been postulated to account for the unique characteristics of the opioid receptor defined as a putative epsilon-opioid receptor. Many epsilon-opioid receptors are functionally coupled to G-proteins. The functional epsilon-opioid receptors in the brain are stimulated by bremazocine and etorphine as well as beta-endorphin, but not by selective mu-, delta- or kappa-opioid receptor agonists. Epsilon-opioid receptor agonists injected into the brain produce profound antinociception. The brain sites most sensitive to epsilon-agonist-induced antinociception are located in the caudal medial medulla such as the nucleus raphe obscures, nucleus raphe pallidus and the adjacent midline reticular formation. The stimulation of epsilon-opioid receptors in the brain facilitates the descending enkephalinergic pathway, which probably originates from the brainstem terminating at the spinal cord. The endogenous opioid Met-enkephalin, released in the spinal cord by activation of supraspinal epsilon-opioid receptors, stimulates spinal delta2-opioid receptors for the production of antinociception. It is noteworthy that the epsilon-opioid receptor-mediated pain control system is different from that of other opioid systems. Although there appears to be no epsilon-selective ligand currently available, these findings provide strong evidence for the existence of the putative epsilon-opioid receptor and its unique function in the brain.
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PMID:Evidence for the existence of the beta-endorphin-sensitive "epsilon-opioid receptor" in the brain: the mechanisms of epsilon-mediated antinociception. 959 17


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