Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this review was to identify and analyze the controlled clinical trial data for peripheral neuropathic pain (PNP) and complex regional pain syndromes (CRPS). A total of 72 articles were found, which included 92 controlled drug trials using 48 different treatments. The methods of these studies were critically reviewed and the results summarized and compared. The PNP trial literature gave consistent support (two or more trials) for the analgesic effectiveness of tricyclic antidepressants, intravenous and topical lidocaine, intravenous ketamine, carbamazepine and topical aspirin. There was limited support (one trial) for the analgesic effectiveness of oral, topical and epidural clonidine and for subcutaneous ketamine. The trial data were contradictory for mexiletine, phenytoin, topical capsaicin, oral non-steroidal anti-inflammatory medication, and intravenous morphine. Analysis of the trial methods indicated that mexiletine and intravenous morphine were probably effective analgesics for PNP, while non-steroidals were probably ineffective. Codeine, magnesium chloride, propranolol, lorazepam, and intravenous phentolamine all failed to provide analgesia in single trials. There were no long-term data supporting the analgesic effectiveness of any drug and the etiology of the neuropathy did not predict treatment outcome. Review of the controlled trial literature for CRPS identified several potential problems with current clinical practices. The trial data only gave consistent support for analgesia with corticosteroids, which had long-term effectiveness. There was limited support for the analgesic effectiveness of topical dimethylsulfoxyde (DMSO), epidural clonidine and intravenous regional blocks (IVRBs) with bretylium and ketanserin. The trial data were contradictory for intranasal calcitonin and intravenous phentolamine and analysis of the trial methods indicated that both treatments were probably ineffective for most patients. There were consistent trial data indicating that guanethidine and reserpine IVRBs were ineffective, and limited trial data indicating that droperidol and atropine IVRBs were ineffective. No placebo controlled data were available to evaluated sympathetic ganglion blocks (SGBs) with local anesthetics, surgical sympathectomy, or physical therapy. Only the capsaicin trials presented data which allowed for meta-analysis. This meta-analysis demonstrated a significant capsaicin effect with a pooled odds ratio of 2.35 (95% confidence intervals 1.48, 3.22). The methods scores were higher (P < 0.01) for the PNP trials (66.2 +/- 1.5, n = 66) than the CRPS trials (57.6 +/- 2.9, n = 26). The CRPS trials tended to use less subjects and were less likely to use placebo controls, double-blinding, or perform statistical tests for differences in outcome measures between groups. There was almost no overlap in the controlled trial literature between treatments for PNP and CRPS, and treatments used in both conditions (intravenous phentolamine and epidural clonidine) had similar results.
 ...
PMID:A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. 1006 78

To delineate fully opioid peptide function in cutaneous inflammatory and nociceptive responses, it is necessary to know first which opioid peptides are present in the skin and which cellular elements in the skin store and secrete them. Merkel cells are cutaneous neuroendocrine cells, which may derive from the neural crest or from undifferentiated keratinocytes with stem cell character. The neuroendocrine character of Merkel cells is supported by their immunoreactivity for chromogranin A (CGA) and a variety of neuropeptides, among them the opioid peptide [Met]enkephalin as shown in guinea-pig and mouse. This study investigates in the rat whether the preprodynorphin derived opioid peptide dynorphin A is expressed in cutaneous Merkel cells and possibly related to an aminergic phenotype. Light microscopic immunohistochemistry revealed dynorphin A immunoreactivity in Merkel cells to be codistributed with immunoreactivity for calcitonin gene-related peptide (CGRP) and CGA, two well-established merker peptides of mammalian Merkel cells. Vibrissal Merkel cells stained for the neuroendocrine vesicular monoamine transporter isoform 1 (VMAT1) but not for the predominantly neuronal isoform 2 (VMAT2). Merkel cell staining for dynorphin A, VMAT1, CGA, and CGRP was unaffected by experimental denervation. Dynorphin A and a still unidentified monoamine, possibly serotonin, may cofunction as autocrine or paracrine mediators in the mechanosensory Merkel cell--axon complex and are potentially involved in peripheral analgesia.
 ...
PMID:Cutaneous Merkel cells of the rat contain both dynorphin A and vesicular monoamine transporter type 1 (VMAT1) immunoreactivity. 967 97

Explants of tissue derived from the medial collateral ligament (MCL) of normal and pregnant NZW rabbits cultured in the presence of substance P (SP), calcitonin gene-related peptide (CGRP), or both neuropeptides were found to have altered mRNA levels for a number of relevant molecules. Using a very efficient RNA isolation method, semi-quantitative RT-PCR and rabbit-specific primers, mRNA for growth factors (TGFbeta, bFGF, IGF-2, ET-1), cytokines (IL-1, TNF), enzymes (COX-2, iNOS), metalloproteinases (collagenase, stromelysin) and metalloproteinase inhibitors (TIMP-1, TIMP-2) were assessed after culture with or without neuropeptide. The results indicate that SP was effective in lowering mRNA levels for all of the molecules assessed in RNA from normal ligaments except IL-1beta, IGF-2 and TIMP-1, for which there was no significant effect. Similarly, CGRP was effective in lowering mRNA levels for all molecules except TNF, ET-1 and the TIMPs. The extent of the lowering of mRNA levels was both molecule-specific and neuropeptide-specific. When the experiments were repeated with ligament tissue from pregnant animals, a very different pattern of responsiveness to the neuropeptides was observed. While mRNA levels for 9/12 genes assessed were significantly affected by SP when normal MCL tissue was investigated, pregnancy abolished all significant responsiveness to this neuropeptide except for iNOS mRNA levels. In the case of iNOS mRNA, SP induced an increase in the steady-state levels, the opposite to what was observed with tissue from non-pregnant animals. For CGRP and SP+CGRP, tissue from pregnant animals was still responsive, but the pattern of responsiveness was changed from strictly a lowering of steady-state mRNA levels to elevations in mRNA levels for a number of genes. These findings indicate that mRNA levels for a number of genes can be influenced by neuropeptides known to be in ligaments. Thus, neuropeptides likely are important regulators of ligament cell metabolism. As the responsiveness to SP was nearly completely abolished during pregnancy, neuroregulatory influences mediated by this peptide are altered in the pregnant female. This loss of responsiveness to SP may also be one aspect of the analgesia associated with pregnancy.
 ...
PMID:Pregnancy alters the in vitro responsiveness of the rabbit medial collateral ligament to neuropeptides: effect on mRNA levels for growth factors, cytokines, iNOS, COX-2, metalloproteinases and TIMPs. 978 99

A 39-year-old patient developed phantom pain after amputation of both upper arms following a burn injury. The pain did not respond to naproxen, morphine, carbamazepine, amitriptyline, calcitonin or transcutaneous electrical nerve stimulation (TENS). At the 39th post-operative day an axillary catheter was placed on the right side, as well as an interscalene catheter on the left. Ropivacaine 0.2% was infused, starting with a rate of 4 ml/h, that was increased to 6 ml/h during the subsequent 6 days. Within 20 min of catheter placement complete pain relief was achieved. The patient did not need any other analgesics and remained painfree for 7 months. Neither motor block, nor any other side effects occurred during the infusion of ropivacaine 0.2%. Thus, the patient not only received analgesia, but also got an effective treatment of established phantom pain. A similar approach with bupivacaine may not have been feasible, because of the possibility of toxic side effects. Ropivacaine is a long-acting local anaesthetic which is less toxic than bupivacaine and has the additional advantage of producing less motor-blockade in the concentration used, so the patient was able to move actively without experiencing any pain.
 ...
PMID:Continuous blockade of both brachial plexus with ropivacaine in phantom pain: a case report. 983 24

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing mu-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or delta-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.
 ...
PMID:Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia. 987 49

Calcitonin is one of three most important factors involved in the regulation of systemic calcium homeostasis. Since its discovery in 1961 the structure of calcitonin from different species including human was established, synthetized and developed for use in human clinic. Up to now calcitonin is utilized in treatment of hypercalcemia, Paget disease, algodystrophy, primary and secondary osteoporosis and analgesia. Beside comparative studies aiming on selection of the most effective protocol of treatment and utilization, lately calcitonin is extensively studies for its antifracture potency in osteoporosis. One of the substantial therapeutical progress also appeared the utilization of intransal preparation of calcitonin.
 ...
PMID:[Calcitonin -- 1998]. 1010 52

A homozygous CGRP-/- mouse line was generated by the targeted disruption of exon 5 in the calcitonin/alphaCGRP gene using homologous recombination. The mutant mice lack alphaCGRP mRNA. Furthermore CGRP immunoreactivity almost completely disappears from the spinal cord and is not at all observed in spinal ganglia and muscle synapses. However, motor end plates were still detected by acetylcholinesterase staining. Antinociceptive behavior tested by the tail flick and hot plate tests did not significantly differ in mutant and wild-type mice, except when challenged by morphine. Paradoxically, morphine analgesia was reduced in mutant mice compared with controls in the tail flick test, but not in the hot plate test. Thus, alphaCGRP differentially modulates opiate pain pathways.
 ...
PMID:Modulation of morphine analgesia in alphaCGRP mutant mice. 1020 59

The aim of this paper is to study the influence of salmon calcitonin (SCT) on opioid analgesia when opioid transduction pathways are functionally uncoupled from Gi/o proteins by treatment with pertussis toxin (PTX). The antinociceptive effect of morphine and three selective opioid agonists, [D-Ala2,N-Me-Phe2,Gly5-ol]enkephalin (DAMGO) (OP(3-mu receptor agonist), [D-Pen2.5]-enkephalin (OP-1-delta receptor agonist) and trans-( +/- )-3,4-dichloro-N-methyl-N-[2-1(-pyrrolidinyl)-cyclohexyl]-benzene-acetam ide methane sulfonate (U-50, 488H) (OP1-kappareceptor agonist) was evaluated, using the tail flick test, in mice treated with PTX or with PTX and SCT. PTX blocked the antinociceptive effect of the opioids, being the antinociception similar in control animals and in mice treated with PTX and SCT. Thus, SCT prevents the effect of the blockade of Gi/o-proteins. From this it could be suggested that calcitonin activates alternative antinociceptive mechanisms that are not dependent on Gi/o-proteins.
 ...
PMID:Calcitonin reverts pertussis toxin blockade of the opioid analgesia in mice. 1051 87

The analgesic effect of calcitonin when serotonin (5-HT) concentration is increased and the involvement of some 5-HT receptors were studied using the writhing test in mice. 5-hydroxytryptophan (5-HTP) administration increased both 5-HT levels in the central nervous system (CNS) and calcitonin analgesia. The 5-HT(1A) agonist (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) diminished calcitonin analgesia, this effect being antagonised by the 5-HT(1A) antagonist (WAY 100, 135). As the stimulation of 5-HT(1A) autoreceptors reduces the turnover of 5-HT, the effect of 8-OH-DPAT on calcitonin analgesia may be attributed to this decrease. The 5-HT(2A-2C) agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) diminished calcitonin analgesia. A sub-analgesic dose of the 5-HT(2A) antagonist ketanserin failed to prevent this effect. The 5-HT(3) agonist (+/-)-2-methyl-5-hydroxytryptamine maleate (2-methyl-5-HT) potentiated calcitonin analgesia, whereas it was significantly reduced by the 5-HT(3) antagonist tropisetron. The effect of 2-methyl-5-HT on calcitonin analgesia was also reversed by tropisetron, This result suggests that the 5-HT(3) receptor may play an important role in the relationship between calcitonin and the serotonergic system. Tropisetron also reversed the analgesia induced by calcitonin plus 5-HTP corroborating importance of the 5-HT(3) receptors.
 ...
PMID:Study of mechanisms of calcitonin analgesia in mice. Involvement of 5-HT3 receptors. 1053 92

We investigated the antinociceptive effect of systemic injection of calcitonin and its mechanisms of action in rats. Subcutaneous injection of [Asu(1,7)]eel calcitonin (ECT, 4 U x kg(-1) x day(-1)) daily for 7 days suppressed nociceptive hypersensitivity induced by formalin (and by carrageenan); the effect was gradually increased by the repeated injections and significant effects were observed after administration for more than 4 days. The antinociceptive action of ECT (4 U x kg(-1) x day(-1) for 7 days) was inhibited by intracerebroventricular injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine and serotonin-receptor antagonists methiothepin, cyproheptadine and ketanserin; methysergide showed an inhibitory tendency. Intrathecal injections of 5,7-dihydroxytryptamine, methiothepin, cyproheptadine and ketanserin were without effects on the ECT action. The results suggest the involvement of serotonin in the brain, but not in the spinal cord, in the ECT antinociception. Intracerebroventricular or intrathecal injection of the catecholaminergic neurotoxin 6-hydroxydopamine and intracerebroventricular injection of the alpha-adrenoceptor antagonist phentolamine were also without effects on the ECT action. A subcutaneous infusion of the opioid receptor antagonist naloxone inhibited the antinociceptive action of morphine, but not that of ECT. Thus, adrenergic and opioidergic systems may not play important roles in the ECT antinociception. The present results suggest that repeated systemic injection of ECT produces analgesia and that the brain serotonergic terminals are involved in this action.
 ...
PMID:Involvement of brain serotonergic terminals in the antinociceptive action of peripherally applied calcitonin. 1066 42


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