Humans ; Dynorphins/metabolism* ; Receptors, Opioid, kappa/metabolism* ; Cryoelectron Microscopy

Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.
Adult ; Dynorphins ; Fertility ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism ; Hypothalamus ; Infertility ; Kisspeptins ; Mammals ; Neurokinin B ; Neuropeptides ; Nutritional Status ; Axis, Cervical Vertebra

OBJECTIVETo observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR).

RESULTSCompared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level.

CONCLUSIONThe intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.

Acupuncture Analgesia ; Acupuncture Points ; Analgesics, Opioid ; immunology ; Animals ; Arthritis, Rheumatoid ; immunology ; therapy ; Cattle ; Chronic Pain ; immunology ; therapy ; Dynorphins ; genetics ; immunology ; Electroacupuncture ; Enkephalin, Methionine ; genetics ; immunology ; Humans ; Male ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; genetics ; immunology ; Synovial Fluid ; immunology ; beta-Endorphin ; genetics ; immunology

Animals ; Dynorphins ; metabolism ; Parkinson Disease ; drug therapy ; metabolism ; Peptides ; pharmacology ; Rats ; Scorpion Venoms ; pharmacology

Perioperative opioid-induced hyperalgesia (OIH) can be defined as the "increased perception of pain after opioid-based anesthesia and surgery" since hyperalgesia is defined as "increased pain from a stimulus that normally provokes pain." OIH has been identified mainly after remifentanil-based anesthesia in surgical patients given the high dose and rapid withdrawal used. The mechanisms of OIH have been postulated mainly by the cellular-level adaptation in internalization of the receptors and downregulation of intracellular coupling, upregulation of spinal dynorphins, and activation of N-methyl-D-aspartate receptors have been postulated as well. The clinical aspects of OIH with various causes, especially remifentanil, have been investigated. Pros and cons related to remifentanil-induced hyperalgesia have been suggested. The dose and duration of remifentanil used in surgery and anesthesia can be the appropriate factors for OIH, including the way of setting for the control groups of those studies, and the methods for evaluating the pain. Opioids remain one of the most powerful pain killers for acute pain management. Opioids are sometimes necessary for perioperative analgesia, but OIH can be an unavoidable risk. Ongoing interest in OIH and the development of anesthesia optimized for its prevention will increase the quality of perioperative life.
Acute Pain ; Analgesia ; Analgesics, Opioid ; Anesthesia ; Down-Regulation ; Drug Tolerance ; Dynorphins ; Humans ; Hyperalgesia* ; Methods ; Receptors, N-Methyl-D-Aspartate ; Up-Regulation

The worldwide use of opiates is increasing yet there is little evidence that in long-term, non-cancer patients, they have an efficacious effect on functional outcomes and quality of life measures. Although it seems paradoxical, chronic opiate use may lead to a pro-nociceptive state. Mechanisms for the development of the hyperalgesic state include activation of the opiate bimodal regulatory systems, dynorphin and spinal cord glia. A potential consequence of chronic opiate usage is the development of narcotic bowel syndrome, which is characterized by chronic or intermittent colicky abdominal pain or discomfort that worsens after the narcotic effects of opiates wear off. It is likely that this is an under-recognized diagnosis. We describe here a case of 26-year old female who had visited our institution multiple times with intractable chronic abdominal pain in the context of normal findings on haematological, biochemical, metabolic, endoscopic and radiological investigations. She had been treated with a multitude of opioid agonists with escalating doses. A diagnosis of narcotic bowel syndrome was made. On elective admission her daily analgesic requirements were 150 microg/hr fentanyl, 100 mg oramorph and 400 mg tramadol (equating to 740 mg oral morphine/24 hr). A detoxification regimen was prescribed which included rapid opiate withdrawal couple with the commencement of methadone, lorazepam, clonidine and duloxetine. She was discharged opiate free, with no abdominal pain, 14 days after admission. Clinicians must be aware of narcotic bowel syndrome, which is often erroneously labelled as a functional gastrointestinal disorder, in patients who have been on long-term opiates.
Abdominal Pain ; Analgesics ; Analgesics, Opioid ; Clonidine ; Dynorphins ; Female ; Fentanyl ; Gastrointestinal Diseases ; Gastrointestinal Tract ; Humans ; Lorazepam ; Methadone ; Narcotics ; Neuroglia ; Quality of Life ; Spinal Cord ; Thiophenes ; Tramadol ; Duloxetine Hydrochloride

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.
Calcium ; Cytoplasm ; Dynorphins ; Methoxyhydroxyphenylglycol ; Neurons ; Potassium Channels ; Presenilins ; Proteins ; Receptors, Metabotropic Glutamate ; Up-Regulation

OBJECTIVETo explore the clinical effect and mechanism of electroacupuncture at Jiaji (EX-B 2) on drug craving of heroin addicts.

METHODSOne hundred and twenty cases of heroin addicts were randomly divided into 4 groups, 30 cases in each. In acupuncture group 1, the Jiaji (EX-B 2) points of T5-T7 and Shenshu (BL 23) were selected with electroacupuncture; in acupuncture group 2, Neiguan (PC 6), Shenmen (HT 7) and Zusanli (ST 36) etc. were selected with electroacupuncture; in simulation group, Zusanli (ST 36) and Sanyinjiao (SP 6) were selected with analog electrical stimulation, and in blank group no any therapy was applied. The changes of drug craving were evaluated by Visual Analogue Scale (VAS) and the changes of beta-EP and Dyn-A in plasma before and after treatment were tested by radioimmunoassay.

RESULTSThe relapse rate of 77.3% (17/22) in acupuncture group 1 was lower than those of 88.5% (23/26) in acupuncture group 2, 90.5% (19/21) in simulation group and 95.7% (22/23) in blank group (all P < 0.05). At the 8th and 10th week of treatment, the VAS scores in acupuncture group 1 and 2 were much lower than those in blank group and simulation group (all P < 0.01); in which, it was lower in acupuncture group 1 than that in acupuncture group 2 (P < 0.05), and lower in simulation group than that in blank group. After 10 weeks of treatment, compared with the status before treatment, beta-EP and Dyn-A in plasma were increased in acupuncture group 1 and 2 (P < 0.05, P < 0.01), Dyn-A was decreased in both simulation and blank groups (both P < 0. 01) which was less obvious than those in both acupuncture groups (both P < 0.01) and superior in acupuncture group 1 than that in group 2 (P < 0.05).

CONCLUSIONElectroacupuncture at Jiaji (EX-B 2) can suppress the drug craving and reduce the relapse rate, and the mechanism may be related with the content of beta-EP, especially the increase of Dyn-A in plasma.

Acupuncture Points ; Adolescent ; Adult ; Dynorphins ; blood ; Electroacupuncture ; Female ; Heroin Dependence ; blood ; psychology ; therapy ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; beta-Endorphin ; blood

OBJECTIVETo explore the mechanism of Chinese medicinal therapy for nourishing blood and softening Gan in treating senile pruritus through observing the impact of Guishen Zhiyang Recipe (GZR) on serum levels of stem cell factor (SCF) and dynorphin (DYN) in patients suffered from the disease of blood-deficiency and Gan-hyperactive syndrome type (BDGH).

METHODSSixty patients with senile pruritus were equally randomized into two groups, the patients in the treated group (33 cases) were treated by GZR, and those in the control group (28 cases) were treated by Fuyang Granule, all for 8 weeks. Changes of symptoms and skin lesions as well as blood levels of SCF and DYN were observed before and after treatment.

RESULTSThree patients were rejected from the treated group. Twenty patients in the treated group were cured after treatment, the cure rate being 66.7%, which was significantly higher than that in the control group (10 patients, 35.7%, P < 0.05). Levels of SCF and DYN in the treated group significantly lowered after treatment (all P < 0.01), and were lower than those in the control group (P < 0.05 and P < 0.01, respectively).

CONCLUSIONGZR shows favorite effect in treating senile pruritus of BDGH type and it may be achieved by regulating SCF and DYN levels to improve the pruritus associated inflammatory media.

Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Dynorphins ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Pruritus ; drug therapy ; metabolism ; Stem Cell Factor ; metabolism ; Syndrome

BACKGROUND: Dynorphin A (1-17) is conceived as an endogenous opioid peptide with a high degree of selectivity forkappa- opioid receptor even though it has been reported to sometimes act like amicro- opioid agonist. The aim of this study was to investigate [35S] GTPgammaS binding stimulated activation by dynorphin A (1-17) in the cerebral and thalamic membranes of a rhesus monkey. METHODS: The rhesus monkey (Macaca mulatta, male, n = 1) was euthanized for the preparation of the cerebral and thalamic membranes. Protein concentrations were determined by the Bradford method. In the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve, EC50 (effective concentration 50 nM) and maximum stimulation (% over basal) were determined in the absence or presence of themicro-andkappa-opioid receptor antagonists naloxone (20 nM) and norbinaltorphimine (nor-BNI, 3 nM), respectively. E2078-stimulated [35S] GTPgammaS binding was also determined in the absence or presence ofmicro-andkappa-opioid receptor antagonists in the cortical membrane and compared with dynorphin A (1-17). RESULTS: Values of EC50 and maximum stimulation of dynorphin A (1-17)-stimulated [35S] GTPgammaS binding were as follows: cortex (474 nM/32.0%) and thalamus (423 nM/45.3%). Nor-BNI (3 nM) did not antagonize dynorphin A (1-17)-stimulated [35S] GTPgammaS binding at all in cortical or thalamic membrane, but naloxone (20 nM) produced a 12.2 fold rightward shift of the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve in the thalamic membrane. The EC50 and the maximum stimulation of E2078-stimulated [35S] GTPgammaS binding were 65.6 nM and 22.7%, respectively. In E2078-stimulated [35S] GTPgammaS binding, the dose-response curve was antagonized not by nor-BNI but by naloxone but in the cortical membrane (a 14.2 times rightward shift). CONCLUSIONS: Dynorphin A (1-17) is selective formicro-opioid receptor in agonist-stimulated [35S] GTPgammaS binding in the cortical and thalamic membranes of rhesus monkey.
Dynorphins* ; Guanosine 5'-O-(3-Thiotriphosphate)* ; Haplorhini* ; Humans ; Macaca mulatta ; Male ; Membranes* ; Naloxone ; Opioid Peptides ; Receptors, Opioid ; Thalamus