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)

Algodystrophy is a complex and heterogenous syndrome, better defined as a subtype of Reflex Sympathetic Dystrophy syndrome (RSD). The pathophysiological theory of RSD has been supported by basic studies and clinical efficacy of sympathetic blocks. Results may be good, but some of RSD are not responsive to sympathetic blocks, and distinction between sympathetic dependent and independent pain has been proposed as subtypes of RSD. Physiotherapy is an essential part of RSD treatment. Sympathetic blocks and other analgesic therapies are performed in order to permit painless action of the physiotherapy against sick limbs stiffness. The rule must be: no painful physiotherapy. Use of other kind of drugs has yet to be defined. Calcitonin is potentially beneficial, but must be given in combination with blocks. Some new treatments rise interesting fundamental questions and some of them are under evaluation. Psychological support is the third part of treatment of these chronic pain patients. Multidisciplinary organisation, as offered by pain centers, can help to understand this syndrome and to elaborate guidelines for diagnosis, treatment and research programs.
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PMID:[Treatment of algodystrophies. The point of view of an anesthetist]. 850 50

Calcitonin gene-related peptide (CGRP), which has been observed in different parts of the nervous system, is known to modify pain sensitivity to different stimuli in rats and mice. The aim of this study was to investigate the possible interaction of CGRP with morphine on nociception in adult male NMRI mice after central administration of the peptide. CGRP (20 or 200 ng) did not itself modify pain sensitivity in the tail-flick test and did not affect the acute antinociceptive action of a single dose of morphine in the same test. However, CGRP suppressed the development of rapid tolerance to morphine in a dose-dependent manner, but had no action on the development of chronic tolerance to morphine and on manifestations of naloxone-precipitated withdrawal syndrome.
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PMID:Effects of calcitonin gene-related peptide on acute and chronic effects of morphine. 854 80

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

Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been implicated in the transmission and modulation of primary afferent nociceptive stimuli. In this study, we describe the light microscopic distribution of CGRP immunoreactivity (IR) within the feline trigeminal ganglion and trigeminal nucleus of normal adult subjects and in subjects 10 and 30 days following complete retrogasserian rhizotomy. Within the trigeminal ganglion of normal subjects, cell bodies and fibers showed CGRP-IR, whereas immunoreactive fibers were rare in the central root region. Within the normal spinal trigeminal and main sensory nuclei, CGRP-IR was seen to form a reproducible pattern that varied between the different nuclei. Following rhizotomy, most, but not all, of the CGRP-IR was lost from the spinal trigeminal and main sensory nuclei, except in regions where the upper cervical roots and cranial nerves VII, IX and X project into the trigeminal nucleus. The pattern seen at 10 days contained more CGRP-IR than that seen at 30 days and suggests that degenerating fibers still show CGRP-IR. In contrast to the decrease seen in the nuclei after rhizotomy, examination of the central root that was still attached to the trigeminal ganglion showed an increase in CGRP-IR within fibers, some of which ended in growth conelike enlargements. Rhizotomy induced a dramatic increase in CGRP-IR within trigeminal motoneurons and their fibers, which was strongest 10 days after rhizotomy and weaker at 30 days, which was still stronger than normal. These results indicate that the majority of CGRP-IR found in the trigeminal nucleus originates from trigeminal primary afferents and that an upregulation of CGRP-IR occurs in trigeminal motoneurons and in regenerating fibers in the part of the central root that was still attached to the ganglion. In addition, the persistence of CGRP-IR fibers in the trigeminal nucleus provides one possible explanation for the preservation of pain in humans following trigeminal rhizotomy.
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PMID:Light microscopic localization of calcitonin gene-related peptide in the normal feline trigeminal system and following retrogasserian rhizotomy. 874

Calcitonin gene related peptide (CGRP), one of the most abundant peptides in the spinal cord, is localized in primary afferents and released following nociceptive stimuli. Its colocalization and corelease with substance P, a well-known nociceptive neuropeptide, support the importance of CGRP in pain mechanisms. However, its distinctive function in that regard remains to be fully established. Recently, we reported that increases in CGRP-like immunostaining and decrements in specific 125I-labelled human CGRP alpha ([125I]hCGRP alpha) binding sites in the spinal cord were correlated with the development of tolerance to the spinal antinociceptive action of a mu opioid agonist, morphine. The goal of the present study was to investigate whether the development of tolerance to other classes of opioids, namely, delta and kappa agonists, can also alter CGRP-like immunostaining and receptors in the rat spinal cord. The antinociceptive effects of all opioids were monitored by the tail-immersion test. Tolerance to their antinociceptive properties was induced by the infusion for 7 days of mu (morphine sulfate, 7.5 micrograms/h), delta D([D-Pen2,D-Pen5]enkephalin (DPDPE), 2.0 micrograms/h), and kappa (U-50488H, 10.0 micrograms/h) related agonists at the spinal level (L4), using osmotic minipumps. We confirmed that rats chronically treated with morphine showed significant decreases in [125I]CGRP alpha binding in laminae I, II, and III of the L4 spinal cord, while CGRP-like immunostaining was increased in these same laminae. Similar effects were observed following a treatment with the delta agonist, DPDPE, while the kappa agonist, U-50488H, apparently only slightly decreased [125I]CGRP alpha] binding in lamina II. Binding in other laminae and CGRP-like immunostaining were not affected. These results suggest a specific interaction between spinal CGRP systems and the development of tolerance to the spinal antinociceptive effects of mu- and delta-related agonists.
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PMID:Alteration of calcitonin gene related peptide and its receptor binding sites during the development of tolerance to mu and delta opioids. 884 7

Reflex sympathetic dystrophy presents with pain out of proportion to the cause, loss of function, and significant evidence of an autonomic disorder. These findings are often accompanied by psychological disturbances, which can dominate the condition. There are differences in the symptoms and signs during childhood. It is more frequent among girls than boys, and the legs are more often affected than the arms; and trophic changes may be absent. There may be no history of trauma, and the response to treatment is often satisfactory. There are a number of theories on etiology. A disorder of the sympathetic nervous system with increased activity has been suggested, but on the evidence available super-sensitivity to neurotransmitters is more likely. Also there may be a spinal, as well as a peripheral, component to the sensitivity. Other suggestions include the release of a pain substance, a disturbance of natural opioid metabolism, and an exaggerated inflammatory response. The diagnosis is mainly clinical, supported by X-ray examination, bone scans with Technetium 99m labelled diphosphonates, and a characteristic scintograph pattern. Laser Doppler flowmetry can also, be useful. The most effective preventative measure is control of pain and early mobilisation. Many treatments have been tried, but the response is variable. Drugs include analgesics, non-steroid anti-inflammatory drugs, anti-depressants, and steroids. Betablockers, with gradually increasing doses may help; as may vasodilators. Calcitonin, by intramuscular injection has been given a particularly favourable report. Physiotherapy is of prime importance. Some treatments are only likely to be considered in older children. Blocking of sympathetic pathways can be tried with paravertebral or epidural injections of local anesthetics. Regional intravenous injections of alpha adrenergic blocking agents distal to a tourniquet can relieve pain, but usually only transiently; and ketanserin may act favourably as a serotonin antagonist. Surgical sympathectomy can also be considered.
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PMID:Reflex sympathetic dystrophy. 887 43

Major complications arising from diabetes mellitus include neuropathic pain and altered peripheral inflammatory responses. Somatostatin (SOM), calcitenin gene-related peptide (CGRP), and substance P (SP) are neuropeptides that modulate pain responses transmitted by primary sensory afferents, the cell bodies of which are located in the dorsal root ganglion (DRG). Thus, the goal of the present study was to determine whether the diabetic condition is associated with altered neuropeptide gene expression in lumbar DRG of the rat. We employed an established animal model in which streptozotocin (STZ, 55 mg/kg) is administered to 6 week-old rats. The hallmark symptoms of hyperglycemia (blood glucose > 400 mg/dl), polydipsia, polyuria, and severe weight loss were maximal at 6 weeks postadministration, at which time animals were sacrificed. For determination of peptide encoding mRNAs distributed in DRG neurons, in situ hybridization histochemistry utilizing S-end-labeled oligonucleotides complimentary to sequences of preprosomatostatin (PPSOM), preprocalcitonin gene related peptide (PPCGRP), preprotachykinin (PPT), or preproneuropeptide Y (PPNPY) mRNA was performed. Silver grains were detected overlying DRG cells by autoradiography on sections of tissue counterstained with thionin. Semiquantitative analysis of differences in silver grain signal were made using an image analysis system, which expressed signals as fCi/microns2. In diabetic rats there was a significant decrease in DRG PPSOM (54%, p < 0.01), and PPCGRP (33%. p < 0.05) mRNA hybridization from the normal values PPT mRNA hybridization signal and SP-like immunoreactivity were not significantly changed in diabetic rat DRGs compared to control. In contrast, there was an increase in the number of cells labeled with PPNPY hybridization in DRG from diabetic rats. These data suggest that CGRP and SOM synthesis in primary sensory neurons is reduced in STZ-induced diabetic rats. These changes could contribute to the painful neuropathies and altered inflammatory responses seen in diabetes mellitus.
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PMID:Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNAs in rat sensory neurons. 889 22

From 10 to 20% of patients with Paget's disease of bone, including those without patent clinical signs, risk severe neurological, orthopedic or cardiovascular complications. Calcitonin and etidronate were the first drugs allowing a certain degree of control over excessive bone remodeling subsequent to Paget's disease. Further progress has been made with a family of new bisphosphonates (clodronate, pamidronate, tiludronate, alendronate, risedronate, and others). Ideally, treatment should eliminate bone pain, normalize markers, restore normal bone structure, and prevent recurrence and complications. The new generation of bisphosphonates have powerful anti-osteoclasic activity. These easy-to-administer well-tolerated drugs may be indicated in certain asymptomatic patients in the 50-year age range who have active disease and lesions involving the skull (neurological risk) or lower limbs (orthopedic risk). Although there are no data on the cost effectiveness comparing medical or surgical treatment in these forms having reached the stage of complications, the result in terms of pain relief and improved quality of life is real. Further assessment of wider indications for certain non-symptomatic, but threatening forms of the disease, is needed. Prospective studies should focus on medical improvement, quality of life, and cost-effectiveness.
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PMID:[Current options for the treatment of Paget's disease of bone]. 896 89

We have previously described the changes in spinal cord neuropeptides in the unilateral sciatic chronic constriction injury (CCI) model of Bennett and Xie [Pain, 33 (1988) 87-108] at 28 days, a time of maximum mechanical hyperalgesia. In this study we examine the same model 100-120 days post injury by which time resolution of the hyperalgesia and peripheral nerve injury has occurred according to previous studies. Rats underwent either CCI of the sciatic nerve (n = 12) or else sham operation (n = 8) which involved exposure but no ligation of the nerve. Mechanical hyperalgesia was assessed with a Ugo-Basile analgesymeter and immunohistochemistry performed on the spinal cord sections of the animals and quantified using a confocal microscope. At this late time point CCI rats were no longer significantly mechanically hyperalgesic compared to the sham animals (P > or = 0.09). However, examination of the lumbar spinal cord revealed the following changes. (i) The neuropeptides substance P (SP) (P < 0.0001) and galanin (P < 0.003) both showed decreases of about 30% ipsilaterally in immunoreactivity in laminae 1 and 2 of the dorsal horn compared to the sham operated animals. (ii) Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in laminae 1 and 2 showed no significant changes compared to sham animals. (iii) NPY levels in laminae 3 and 4 of the spinal cord showed a 15% increase in immunoreactivity compared to sham animals (P = 0.008). These results indicate that changes in neuronal markers in the spinal cord can persist after apparent resolution of a peripheral nerve injury. We suggest that these changes may form a substrate for subsequent development of abnormal pain states.
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PMID:Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a rat model of mononeuropathy. 901 36

To better understand pathologic processes associated with arthritis of the temporomandibular joint (TMJ), detailed information on the innervation of TMJ tissues in normal as well as arthritic joints is needed. The aim of this study was to describe the normal innervation of the sheep TMJ in preparation for using this animal as a model for the study of the effects of arthritis on joint innervation. The macroscopic and microscopic appearance plus the distribution of neural structures within the TMJ were examined using fluorescence histochemistry (glyoxylic acid), immunohistochemistry (calcitonin gene-related peptide), silver, and gold chloride techniques. Joints from 10 mature merino sheep were studied. Calcitonin gene-related peptide-immunoreactive nerve fibers were found in the capsule and the synovial membrane, but not in the disc. Nerve bundles and single nerve fibers in the capsule, synovial membrane, and the peripheral 2 to 3 mm of the disc were stained by glyoxylic acid. Ruffini, paciniform-type, and Golgi organ nerve endings plus free nerve endings were located in the capsule, with the highest density of nerve endings occurring at the site of attachment of the disc to the capsule. The highest density of neural structures (using gold chloride) was in the posterior part of the joint. The highest density of autonomic fibers (using glyoxylic acid) was in the anterior capsule. The highest density of sensory fibers (using calcitonin gene-related peptide) was in the synovial and subsynovial tissues of the anterior capsule. These results confirm the existence of autonomic and sensory nerves in the capsule, synovial membrane, and peripheral disc in healthy adult sheep.
J Orofac Pain 1996
PMID:Neural structures within the sheep temporomandibular joint. 916 Dec 27


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