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)

PUVA-bath therapy has proven to avoid many side effects associated with oral 8-methoxypsoralen (8-MOP) treatment. In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA-doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA-soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.
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PMID:PUVA-bath photochemotherapy (PUVA-soak therapy) of recalcitrant dermatoses of the palms and soles. 1032 15

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) have the highest affinity and selectivity for the mu-opioid receptor (MOP-R) of all known mammalian opioids. They were isolated from bovine and human brain, and are structurally distinct from the other endogenous opioids. Both EM-1 and EM-2 have potent antinociceptive activity in a variety of animal models of acute, neuropathic and allodynic pain. They regulate cellular signaling processes in a manner consistent with MOP-R-mediated effects. The EMs are implicated in the natural modulation of pain by extensive data localizing EM-like immunoreactivity (EM-LI) near MOP-Rs in several regions of the nervous system known to regulate pain. These include the primary afferents and their terminals in the spinal cord dorsal horn, where EM-2 is well-positioned to modulate pain in its earliest stages of perception. In a nerve-injury model of chronic pain, a loss of spinal EM2-LI occurs concomitant with the onset of chronic pain. The distribution of the EMs in other areas of the nervous system is consistent with a role in the modulation of diverse functions, including autonomic, neuroendocrine and reward functions as well as modulation of responses to pain and stress. Unlike several other mu opioids, the threshold dose of EM-1 for analgesia is well below that for respiratory depression. In addition, rewarding effects of EM-1 can be separated from analgesic effects. These results indicate a favorable therapeutic profile of EM-1 relative to other mu opioids. Thus, the pharmacology and distribution of EMs provide new avenues both for therapeutic development and for understanding the neurobiology of opioids.
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PMID:Isolation and distribution of endomorphins in the central nervous system. 1218 22

It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. In contrast, beta-endorphin exhibits the strongest actions among endogenous opioid peptides mainly through the MOP-R; however, it also shows the distinct pharmacological actions. Recent cloning and expression studies have indicated that MOP-Rs are seven-transmembrane domain receptors whose actions are mediated through activation of heterotrimeric guanine nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs can be measured by assessing agonist-induced stimulation of membrane binding of guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding assay.
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PMID:Differential mechanism of G-protein activation induced by endogenous mu-opioid peptides, endomorphin and beta-endorphin. 1218 27

Endogenous inhibition of inflammatory pain is mediated by leukocytes that secrete opioid peptides upon exposure to stress (cold water swim stress, CWS) or after local injection of corticotropin releasing factor (CRF). Since in early inflammation few opioid-containing leukocytes are detected and since peripheral opioid-mediated antinociception is low we examined whether antinociception could be augmented by increased recruitment of opioid-containing polymorphonuclear cells (PMN). Rats were intraplantarly (i.pl.) injected with Freund's complete adjuvant (FCA) and with the PMN-recruiting chemokine macrophage inflammatory protein-2 (MIP-2, 1-10 microg; control: saline) for 2 h. Intraplantar leukocytes were quantified by flow cytometry. Paw pressure threshold (PPT) was determined before and after exposure to CWS, i.pl. injection of CRF and opioid peptides. Opioid receptors (OR) were measured by binding studies in dorsal root ganglia (DRG) and by immunohistochemistry in the paw. Our studies showed that (i) MIP-2 injection dose-dependently augmented recruitment of PMN and opioid-containing leukocytes (5-fold increase in cells/paw, P < 0.05), (ii) PPT was not different between groups at baseline and after CWS or CRF (maximum MPE: 20+/-2.3-29+/-7.2%, P < 0.05), (iii) injection of opioid peptides dose-dependently increased the PPT (P < 0.05, maximum MPE: and 18+/-2.6-21+/-3.6%), (iv) MOR (micro OR, MOP) binding sites in the ipsilateral DRG were unchanged (24+/-2-22+/-1.2 fmol/mg protein, P < 0.05, ANOVA) and (v) the number of MOR and DOR (delta OR, DOP) stained nerve fibers in peripheral tissue were unaltered (both P > 0.05, t-test). In summary, antinociception during early inflammation is apparently not limited by the number of opioid-containing leukocytes but by OR availability.
Pain 2004 Mar
PMID:Endogenous peripheral antinociception in early inflammation is not limited by the number of opioid-containing leukocytes but by opioid receptor expression. 1510 9

The NOP receptor (formerly referred to as opiate receptor-like 1, ORL-1, LC132, OP(4), or NOP(1)) is a G protein-coupled receptor that shares high homology to the classic opioid MOP, DOP, and KOP (mu, delta, and kappa, respectively) receptors and was first cloned in 1994 by several groups. The NOP receptor remained an orphan receptor until 1995, when the endogenous neuropeptide agonist, known as nociceptin or orphanin FQ (N/OFQ) was isolated. Five years later, a group at Hoffmann-La Roche reported on the selective, nonpeptide NOP agonist Ro 64-6198, which became the most extensively published nonpeptide NOP agonist and a valuable pharmacological tool in determining the potential of the NOP receptor as a therapeutic target. Ro 64-6198 is systemically active and achieves high brain penetration. It has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for the NOP receptor over the classic opioid receptors. Ro 64-6198 ranges from partial to full agonist, depending on the assay. Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia. This review summarizes the pharmacology and preclinical data of Ro 64-6198.
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PMID:The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (opiate receptor-like 1, ORL-1) agonist with diverse preclinical therapeutic activity. 1746 93

Phosphorylation of specific sites in the second intracellular loop and in the C-terminal domain have previously been suggested to cause desensitization and internalization of the mu-opioid receptor (MOP-R). To assess sites of MOP-R phosphorylation in vivo, affinity-purified, phosphoselective antibodies were raised against either phosphothreonine-180 in the second intracellular loop (MOR-P1) or the C-terminal domain of MOP-R containing phosphothreonine-370 and phosphoserine-375 (MOR-P2). We found that MOR-P2-immunoreactivity (IR) was significantly increased within the striatum of wild-type C57BL/6 mice after injection of the agonist fentanyl. Pretreatment with the antagonist naloxone blocked the fentanyl-induced increase. Furthermore, mutant mice lacking MOP-R showed only non-specific nuclear MOR-P2-IR before or after fentanyl treatment, confirming the specificity of the MOR-P2 antibodies. To assess whether MOP-R phosphorylation occurs following endogenous opioid release, we induced chronic neuropathic pain by partial sciatic nerve ligation (pSNL), which caused a significant increase in MOR-P2-IR in the striatum. pSNL also induced signs of mu opioid receptor tolerance demonstrated by a rightward shift in the morphine dose response in the tail withdrawal assay and by a reduction in morphine conditioned place preference (CPP). Mutant mice selectively lacking all forms of the beta-endorphin peptides derived from the proopiomelanocortin (Pomc) gene did not show increased MOR-P2-IR, decreased morphine antinociception, or reduced morphine CPP following pSNL. In contrast gene deletion of either proenkephalin or prodynorphin opioids did not block the effects of pSNL. These results suggest that neuropathic pain caused by pSNL in wild-type mice activates the release of the endogenous opioid beta-endorphin, which subsequently induces MOP-R phosphorylation and opiate tolerance.
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PMID:The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. 1746 16

The endomorphins are endogenous opioids with high affinity and selectivity for the mu opioid receptor (MOR, MOR-1, MOP). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2); EM1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2); EM2) have been localized to many regions of the central nervous system (CNS), including those that regulate antinociception, autonomic function, and reward. Colocalization or shared distribution (overlap) of two neurotransmitters, or a transmitter and its cognate receptor, may imply an interaction of these elements in the regulation of functions mediated in that region. For example, previous evidence of colocalization of EM2 with substance P (SP), calcitonin gene-related peptide (CGRP), and MOR in primary afferent neurons suggested an interaction of these peptides in pain modulation. We therefore investigated the colocalization of EM1 and EM2 with SP, CGRP, and MOR in other areas of the CNS. EM2 was colocalized with SP and CGRP in the nucleus of the solitary tract (NTS) and with SP, CGRP and MOR in the parabrachial nucleus. Several areas in which EM1 and EM2 showed extensive shared distributions, but no detectable colocalization with other signaling molecules, are also described.
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PMID:Colocalization and shared distribution of endomorphins with substance P, calcitonin gene-related peptide, gamma-aminobutyric acid, and the mu opioid receptor. 1749 26

Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in various biological functions including pain. High density of NOP receptor has been found in the ventrolateral periaqueductal gray (vlPAG), the main output pathway involved in descending pain-control system. The aim of our work was to evaluate the involvement of the N/OFQ/NOP system in the modulation of MOP analgesia in the rat vlPAG using UFP-101, a selective NOP antagonist. N/OFQ significantly blocked DAMGO (a selective MOP agonist) analgesia, while UFP-101 enhanced the effect of the opioid given at a subanalgesic dose. These results confirm our hypothesis of an antiopioid role for N/OFQ in the vlPAG.
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PMID:Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia. 1762 12

Contact with plants can cause phototoxic or rarely photoallergic reactions. Phototoxic dermatitis (photophytodermatitis) occurs after contact or ingestion of plants containing furocumarins i.e. psoralens and followed by sun exposure. Skin lesions develop usually after 24-48 hours with erythema, bulla formation, itch or pain, followed by a long lasting hyperpigmentation. Furocumarins can be linear i.e. psoralens (5-MOP, 8-MOP), or angular like angelicin and pimpinellin. Their binding to DNA causes cellular damage. This can happen in florists, gardeners, farmers, horticulturists, food handlers, and botanists. The plants causing phototoxic reaction can vary with the local flora but are commonly a member of the family apiaceae (formerly umbelliferae), family rutaceae, leguminosae and moraceae. The authors give special consideration to the phytophotodermatitis that appeared in their region in spring and summer during a three year period.
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PMID:Phytophotodermatitis in Rijeka region, Croatia. 1913 25

The nociceptin opioid (NOP) receptor is the most recently discovered member of the family of the opioid receptors; its endogenous agonist is the peptide nociceptin. Due to the subsequent elucidation of its physiological role in both central and peripheral nervous system and in some non-neural tissues, there is a rapidly growing interest in the pharmacological application of substances active on this receptor. Despite the current clinical use of a morphinane-based NOP/MOP mixed ligand (buprenorphine) as an analgesic and in the treatment of drug addictions, so far just a few clinical trials have been made with selective NOP ligands. However, the perspective of their utilization is rapidly growing. Agonists can find applications in the treatment of neuropathic pain, anxiety, cough, drug addition, urinary incontinence, anorexia, congestive heart failure, hypertension; and antagonists for pain, depression, Parkinson's disease, obesity, and as memory enhancers. Besides peptide ligands, which are still subjected to many pharmacological investigations, many different chemical classes of NOP ligands have been discovered: piperidines, nortropanes, spiropiperidines, 4-amino-quinolines and quinazolines, and others. The new advances in establishing structure-activity relationships, also with the help of modeling studies, can permit the development of more active and selective molecules.
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PMID:Development of nociceptin receptor (NOP) agonists and antagonists. 2009 19


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