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East Asian Archives of Psychiatry :... Jun 2016Opioid is a popular drug of abuse and addiction. We evaluated acupuncture as a non-pharmacological treatment with a focus on managing withdrawal symptoms. Electrical... (Review)
Review
Opioid is a popular drug of abuse and addiction. We evaluated acupuncture as a non-pharmacological treatment with a focus on managing withdrawal symptoms. Electrical stimulation at a low frequency (2 Hz) accelerates endorphin and encephalin production. High-frequency stimulation (100 Hz) up-regulates the dynorphin level that in turn suppresses withdrawal at the spinal level. The effect of 100-Hz electroacupuncture may be associated with brain-derived neurotrophic factor activation at the ventral tegmental area, down-regulation of cAMP response element-binding protein, and enhanced dynorphin synthesis in the spinal cord, periaqueductal grey, and hypothalamus. Clinical trials of acupuncture for the management of different withdrawal symptoms were reviewed. The potential of acupuncture to allay opioid-associated depression and anxiety, and its possible use as an adjuvant treatment were evident. A lack of effect was indicated for opioid craving. Most studies were hampered by inadequate reporting details and heterogeneity, thus future well-designed studies are needed to confirm the efficacy of acupuncture in opioid addiction treatment.
Topics: Acupuncture Therapy; Adenosine Monophosphate; Animals; Brain-Derived Neurotrophic Factor; Dynorphins; Electroacupuncture; Humans; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 27377488
DOI: No ID Found -
Acta Physiologica (Oxford, England) Mar 2010The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of... (Review)
Review
The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurones promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurones may promote arousal by exciting cortically projecting neurones of the BF. Orexin fibres synapse on BF cholinergic neurones and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurones, induces cortical release of acetylcholine and promotes wakefulness. The orexin neurones also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurones that project to the cortex. Cholinergic neurones were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurones that project to the cortex seem to comprise at least two populations with some directly excited by orexin-A that may represent wake-active, GABAergic neurones, whereas others did not respond to orexin-A but were inhibited by dynorphin and may be sleep-active, GABAergic neurones. This evidence suggests that the BF is a key site through which orexins activate the cortex and promote behavioural arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance.
Topics: Animals; Arousal; Cognition; Drug Synergism; Dynorphins; Electrophysiological Phenomena; Glutamic Acid; Humans; Hypothalamic Hormones; Intracellular Signaling Peptides and Proteins; Melanins; Microdialysis; Models, Neurological; Neurons; Neuropeptides; Neurotransmitter Agents; Orexins; Pituitary Hormones; Prosencephalon; Synaptic Transmission
PubMed: 19723027
DOI: 10.1111/j.1748-1716.2009.02036.x -
Esophagus : Official Journal of the... Jan 2023To explore the relationships between anxiety/depression and NERD, we focused on dynorphin (Dyn), an important member of visceral hypersensitivity, and its related...
BACKGROUND
To explore the relationships between anxiety/depression and NERD, we focused on dynorphin (Dyn), an important member of visceral hypersensitivity, and its related pathways.
METHODS
Pearson's correlation analysis on patients with NERD and in vivo experiment on NERD rat model. Part 1: Pearson's correlation analysis among serum levels of Dyn, clinical symptoms and HADS scores of NERD patients were carried on. Part 2: Wistar rats were randomly divided into 2 groups: control group and model group. The data of pH value, immobility time, serum Dyn concentration, NMDAR1 and SP expression were, respectively, derived from automatic pH recorder, tail suspension test, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence.
RESULTS
Part 1: Pearson's correlation analysis showed that there was a linear correlation between Clinical Symptom (CS) score and HADS score (HAD-A, HAD-D), and the correlation coefficients were 0.385 and 0.273 respectively; the correlation coefficient between lg (Dyn) and lg (CS score) was r = 0.441, P = 0.002; the correlation coefficient between lg(Dyn) and lg (HAD-D score) was r = 0.447, P = 0.002. Part 2: The pH value of the lower esophagus in the model group was lower than that in the control group (P < 0.01). The tail suspension immobility time of model group was significantly longer than that of control group (P < 0.01). The serum Dyn concentration and the expression level of NMDAR1 in spinal cord and SP in lower esophageal mucosa of model group were significantly higher than those of control group (P < 0.05).
CONCLUSION
Increased serum dynorphin level may be a sign of correlation between depression and NERD.
Topics: Animals; Rats; Depression; Dynorphins; Gastroesophageal Reflux; Rats, Wistar
PubMed: 36244036
DOI: 10.1007/s10388-022-00955-0 -
Current Molecular Medicine 2020It is well-established that cardiovascular disease continues to represent a growing health problem and significant effort has been made to elucidate the underlying... (Review)
Review
It is well-established that cardiovascular disease continues to represent a growing health problem and significant effort has been made to elucidate the underlying mechanisms. In this review, we report on past and recent high impact publications in the field of intracrine network signaling, focusing specifically on opioids and their interrelation with key modulators of the cardiovascular system and the onset of related disease. We present an overview of studies outlining the scope of cardiovascular and cerebrovascular processes that are affected by opioids, including heart function, ischemia, reperfusion, and blood flow. Specific emphasis is placed on the importance of dynorphin molecules in cerebrovascular and cardiovascular regulation. Evidence suggests that excessive or insufficient dynorphin could make an important contribution to cardiovascular physiology, yet numerous paradoxical observations frequently impede a clear understanding of the role of dynorphin. Thus, we argue that dynorphin-mediated signaling events for which an immediate regulatory effect is disputed should not be dismissed as unimportant, as they may play a role in cross-talk with other signaling networks. Finally, we consider the most recent evidence on the role of dynorphin during cardiovascular-related inflammation and on the potential value of endogenous and exogenous inhibitors of kappa-opioid receptor, a major dynorphin A receptor, to limit or prevent cardiovascular disease and its related sequelae.
Topics: Amino Acid Sequence; Animals; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Dynorphins; Fetal Development; Humans
PubMed: 31746302
DOI: 10.2174/1566524019666191028122559 -
Current Opinion in Neurobiology Oct 2015There have been many exciting recent advances in our understanding of the molecular and cellular basis of itch. These discoveries cover diverse aspects of itch... (Review)
Review
There have been many exciting recent advances in our understanding of the molecular and cellular basis of itch. These discoveries cover diverse aspects of itch sensation, from the identification of new receptors to the characterization of spinal cord itch circuits. A common thread of these studies is that they demonstrate that itch sensory signals are segregated from input for other somatosensory modalities, such as pain, touch, and thermosensation. This specificity is achieved by the expression of dedicated receptors and transmitters in a select population of sensory neurons which detect pruritogens. Further, recent studies show that itch specificity is maintained in a spinal cord circuit by the utilization of specific neurotransmitters and cognate receptors to convey input along a distinct cellular pathway.
Topics: Animals; Dynorphins; Humans; Pruritus; Receptors, Cytokine; Receptors, G-Protein-Coupled; Sensory Receptor Cells
PubMed: 25700248
DOI: 10.1016/j.conb.2015.01.017 -
Journal of Neurotrauma Jan 2022Traumatic brain injury (TBI) is a serious public health problem associated with numerous physical and neuropsychiatric comorbidities. Chronic pain is prevalent and... (Review)
Review
Traumatic brain injury (TBI) is a serious public health problem associated with numerous physical and neuropsychiatric comorbidities. Chronic pain is prevalent and interferes with post-injury functioning and quality of life, whereas substance use disorder (SUD) is the third most common neuropsychiatric diagnosis after TBI. Neither of these conditions has a clear mechanistic explanation based on the known pathophysiology of TBI. Dynorphin is an endogenous opioid neuropeptide that is significantly dysregulated after TBI. Both dynorphin and its primary receptor, the ĸ-opioid receptor (KOR), are implicated in the neuropathology of chronic pain and SUD. Here, we review the known roles of dynorphin and KORs in chronic pain and SUDs. We synthesize this information with our current understanding of TBI and highlight potential mechanistic parallels between and across conditions that suggest a role for dynorphin in long-term sequelae after TBI. In pain studies, dynorphin/KOR activation has either antinociceptive or pro-nociceptive effects, and there are similarities between the signaling pathways influenced by dynorphin and those underlying development of chronic pain. Moreover, the dynorphin/KOR system is considered a key regulator of the negative affective state that characterizes drug withdrawal and protracted abstinence in SUD, and molecular and neurochemical changes observed during the development of SUD are mirrored by the pathophysiology of TBI. We conclude by proposing hypotheses and directions for future research aimed at elucidating the potential role of dynorphin/KOR in chronic pain and/or SUD after TBI.
Topics: Analgesics, Opioid; Brain Injuries, Traumatic; Chronic Pain; Dynorphins; Humans; Quality of Life; Receptors, Opioid, kappa; Substance-Related Disorders
PubMed: 34751584
DOI: 10.1089/neu.2021.0063 -
Pharmacology & Therapeutics Nov 2007Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that... (Review)
Review
Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety, and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction, suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/kappa-opioid receptor (KOPr) system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/KOPr system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction.
Topics: Alcoholism; Animals; Behavior, Addictive; Brain; Cocaine; Cocaine-Related Disorders; Dynorphins; Ethanol; Humans; Receptors, Opioid, kappa; Substance-Related Disorders; Up-Regulation
PubMed: 17868902
DOI: 10.1016/j.pharmthera.2007.06.011 -
Neuroscience Letters Jun 2008The endogenous opioid peptide dynorphin A is distinct from other endogenous opioid peptides in having significant neuronal excitatory and neurotoxic effects that are not... (Review)
Review
The endogenous opioid peptide dynorphin A is distinct from other endogenous opioid peptides in having significant neuronal excitatory and neurotoxic effects that are not mediated by opioid receptors. Some of these non-opioid actions of dynorphin contribute to the development of abnormal pain resulting from a number of pathological conditions. Identifying the mechanisms and the sites of action of dynorphin is essential for understanding the pathophysiology of dynorphin and for exploring novel therapeutic targets for pain. This review will discuss the mechanisms that have been proposed and the recent finding that spinal dynorphin may be an endogenous ligand of bradykinin receptors under pathological conditions to promote pain.
Topics: Animals; Dynorphins; Humans; Pain; Receptors, Bradykinin; Spinal Cord
PubMed: 18450375
DOI: 10.1016/j.neulet.2008.03.088 -
Current Biology : CB Oct 2021Discrimination between predictive and non-predictive threat stimuli decreases as threat intensity increases. The central mechanisms that mediate the transition from...
Discrimination between predictive and non-predictive threat stimuli decreases as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identify several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted "U" relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization.
Topics: Dorsal Raphe Nucleus; Dynorphins; Receptors, Opioid, kappa; Septal Nuclei; Ventral Tegmental Area
PubMed: 34388372
DOI: 10.1016/j.cub.2021.07.047 -
Handbook of Experimental Pharmacology 2022Drug addiction is a complex, persistent, and chronically relapsing neurological disorder exacerbated by acute and chronic stress. It is well known that the...
Drug addiction is a complex, persistent, and chronically relapsing neurological disorder exacerbated by acute and chronic stress. It is well known that the dynorphin/kappa opioid receptor (KOR) system regulates stress perception and responsivity, while the mesolimbic dopamine system plays a role in reward and reinforcement associated with alcohol and substance use disorders. Interestingly, the dopamine and dynorphin/KOR systems are highly integrated in mesolimbic areas, with KOR activation leading to inhibition of dopamine release, further altering the perception of reinforcing and aversive stimuli. Chronic or repeated exposure to stress or drugs potentiates KOR function ultimately contributing to a hypodopaminergic state. This hypodopaminergic state is one of the hallmarks of hyperkatifeia, defined as the hypersensitivity to emotional distress that is exacerbated during drug withdrawal and abstinence. The relationship between stress and drug addiction is bidirectional; repeated/chronic stress promotes pro-addictive behaviors, and repeated cycles of drug exposure and withdrawal, across various drug classes, produces stress. Neuroadaptations driven by this bidirectional relationship ultimately influence the perception of the reinforcing value of rewarding stimuli. In this chapter, we address the involvement of the dopamine and dynorphin/KOR systems and their interactions in shaping reinforcement value processing after drug and stress exposure, as well as a combinatorial impact of both drugs and stress.
Topics: Behavior, Addictive; Dopamine; Dynorphins; Humans; Receptors, Opioid, kappa; Reward
PubMed: 33301050
DOI: 10.1007/164_2020_421