- |||||||||| Preclinical, Journal: Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents. (Pubmed Central) - Aug 27, 2024
When combined with central sprouting and loss of descending controls after SCI, this results in exaggerated nociceptive input during stretching. The inability of the applied clinical drugs to mitigate the detrimental effects of stretching highlights the complexity of the stretching phenomenon and emphasizes the need for further investigation.
- |||||||||| 2R,6R-hydroxynorketamine hydrochloride ((2R,6R)-HNK) / National Institute of Mental Health, methionine enkephalin (STAT-401) / Immune Therap, Statera BioPharma, dalargin (leu-enkephalin) / Burnasyan Federal Medical & Biophysical Center
Journal: Ketamine and major ketamine metabolites function as allosteric modulators of opioid receptors. (Pubmed Central) - Aug 27, 2024
All three opioid receptors (mu, delta, and kappa) showed synergism with submicromolar concentrations of ketamine and either Met-enkephalin, Leu-enkephalin, and/or dynorphin A17, albeit the extent of synergy was variable between receptors and peptides...Importantly, the ketamine metabolite 6-hydroxynorketamine showed robust allosteric modulatory activity at mu opioid receptors; this metabolite is known to have analgesic and antidepressant activity but does not bind to glutamate receptors...Significance Statement We found that ketamine and its major biologically-active metabolites function as potent allosteric modulators of mu, delta, and kappa opioid receptors, with submicromolar concentrations of these compounds synergizing with endogenous opioid peptides such as enkephalin and dynorphin. This allosteric activity may contribute to ketamine's therapeutic effectiveness for treating acute and chronic pain and as a fast-acting antidepressant drug.
- |||||||||| morphine sulphate / Generic mfg.
Journal: Symptomatic Recovery from Concussion in Military Service Members with and Without Associated Bodily Injuries. (Pubmed Central) - Aug 26, 2024
Possible reasons suggested for the earlier findings include SMs with bodily injuries report fewer postconcussive symptoms due to (1) focusing attention on extra-cranial injuries and associated pain; (2) receiving more interpersonal and medical support, lowering distress; (3) using analgesics such as morphine or opioids; or (4) experiencing delayed postconcussive symptoms...The level of subjective pain was a determinant of postconcussive symptom severity among SMs with a history of mTBI, with or without associated bodily injuries. Social support was a weaker negative predictor of postconcussive symptoms among SMs with no associated bodily injuries.
- |||||||||| morphine sulphate / Generic mfg., methotrexate / Generic mfg.
Journal: Effective Treatment of Methotrexate Induced Oral Mucositis With a Morphine Mouthwash Solution: A Case Report. (Pubmed Central) - Aug 23, 2024
It is a safer alternative to systemic opioids and topical opioids may influence cell proliferation and migration, which can positively impact healing of oral lesions. A morphine mouthwash solution can provide effective pain management for oral mucositis lesions in patients who do not respond adequately to magic mouthwash.
- |||||||||| morphine sulphate / Generic mfg., buprenorphine transdermal / Generic mfg.
Journal, Adverse events: Long-term efficacy and reduced side-effects of buprenorphine in patients with moderate and severe chronic pain. (Pubmed Central) - Aug 23, 2024
This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development...We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patient-reported outcomes through the Patients' Global Impression of Change (PGIC)...These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations.
- |||||||||| morphine sulphate / Generic mfg.
Investigating opioid activated neurons in the dopaminergic system (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12802;
To examine neurons activated during morphine exposure, we used early gene cFos-linked capture in a transgenic mouse model, as well as where these neurons projected to...The advantage of this study is that our techniques allow us to examine the projections of these neurons, as well as specify differences and similarities among the opioid paradigms. In broadening our understanding of distinct addiction circuitry, targeted therapies for both opioid replacement and opioid addiction may be developed.
- |||||||||| morphine sulphate / Generic mfg.
Social modulation of pain in drug-na (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12782;
These results indicate a female-specific recruitment of the ?-opioid receptor system and impact of specific syllable differences in neonatal opioid withdrawal symptom severity. Homecage behaviour analysis has revealed an increase in isolated behaviours in the drug-na
- |||||||||| morphine sulphate / Generic mfg.
Resource scarcity-induced genomic alterations in the basolateral amygdala: a focus on retrotransposons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12670;
Despite the low nesting materials provided, dams in LBN provide enhanced maternal care and male offspring are less impulsive and self-administer less morphine in adulthood than male rats raised in control housing...We are now extending this research to investigate whether this change is cell-type specific. Understanding whether there are specific cell-types being impacted by LBN is an important step in understanding how early life adversity is directly altering the genome and potentially future behavior.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Orphan receptor GPR139 regulates cholinergic activity in the striatum (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12593;
Preliminary results indicate GPR 139 increases ACh release. Further, consistent with increased cholinergic activity we observe activation of Smo counteracts place preference formation.
- |||||||||| morphine sulphate / Generic mfg.
The impact of morphine on nerve injury recovery and lipid metabolism (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12515;
As oligodendrocytes are the myelinating cells of the CNS, we propose that alterations in lipid metabolism are linked to changes in this cell type. The potential findings could help mitigate adverse opioid effects and improve treatment for people suffering from neuropathic pain.
- |||||||||| morphine sulphate / Generic mfg.
Anti-nociceptive Activity of 80% Methanolic Leaf Extract of Pterolobium stellatum (Forssk.) Brenan (Fabaceae) in Mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12511;
In the hot plate test, compared to the negative control, the 80% methanol extract of P. stellatum leaves at three test doses (100, 200, 400 mg/kg) and the standard drug morphine (5 mg/kg, s.c.) showed a statistically significant delay in response time for pain (p < 0.05) at 30, 60, 90, and 120 min after drug administration...Kaempferol which was component of P. stellatum significantly decreased pain in the acute pain models in other study (Zarei et al., 2023). The present study demonstrated that the extract is harmless in mice, and the data suggest that Pterolobium stellatum leaves hydroalcoholic extract has antinociceptive activity in the hot plate test and formalin test mouse models.
- |||||||||| morphine sulphate / Generic mfg.
Temporal Transcriptomic Changes in Human Nociceptors Following Repeated Opioid Exposure (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12503;
The present study demonstrated that the extract is harmless in mice, and the data suggest that Pterolobium stellatum leaves hydroalcoholic extract has antinociceptive activity in the hot plate test and formalin test mouse models. Here we developed an in vitro model of opioid treatment by exposing human induced pluripotent stem cell (hiPSC)-derived nociceptors to morphine (10
- |||||||||| morphine sulphate / Generic mfg.
Region specific DNA methylome alterations in neonatal rat brain following maternal e-cigarette exposure (MCP Hall A; Virtually Only) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_11614;
Gene ontology analysis revealed that prenatal e-cigarette exposure not only affected GABAergic synapse and cholinergic synapse, but also altered the pathways related to calcium signaling and morphine addiction. In conclusion, this study provides valuable insights into the differential region-specific epigenetic regulation in the developing brain induced by prenatal e-cigarette exposure.
- |||||||||| morphine sulphate / Generic mfg.
Post-operative Cognitive Dysfunction is Exacerbated in a Model of Alzheimer (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9503;
Preliminary findings suggest an exaggeration of POCD in 3xTg-AD compared to non-Tg mice via an impairment in hippocampal-dependent memory assessed by the novel location recognition test. These findings provide a possible avenue of future exploration to identify the mechanism contributing to POCD in a model of AD.
- |||||||||| morphine sulphate / Generic mfg.
Unravelling the role of dopamine and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) in addiction. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7954;
The results from these experiments have provided novel insight into the signalling of DARPP-32 and its downstream signalling partners in the presence of drugs of abuse. They provide additional weighting to the significance of DARPP-32 in the pathophysiology of SUDs through a complete analysis of DARPP-32 from the transcript to post-translational modifications stage.
- |||||||||| morphine sulphate / Generic mfg.
Re-engineered transcription factors reveal's role of ZFP189 in cocaine use disorder (CUD) (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7953;
To further examine the downstream relationship between ZFP189 and physiological response to saline, cocaine, and morphine, three reprogrammed synthetic ZFP189 transcription factors were used to study drug-induced behavior and transcription...Specifically, ZFP189VPR was only able to regulate NAc transcription in mice that had been treated with cocaine. These results suggest ZFP189 specifically drives cocaine-induced transcription and behaviors.
- |||||||||| morphine sulphate / Generic mfg.
Asic1a opposes synaptic and behavioral responses to opioids (MCP Room S103) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7941;
Compared to Asic1a+/+ mice, Asic1a-/- mice had increased locomotor activation to acute administration of oxycodone, morphine, and heroin and increased oxycodone CPP...Additionally, ASIC1A modulates opioid-induced effects on glutamatergic receptors in NAcc MSNs, which may underlie its role in behavior. ASIC1A opposes both behavioral and synaptic effects of opioids, and this work suggests ASIC1A could be a potential therapeutic target for opioid use disorder in humans.
- |||||||||| morphine sulphate / Generic mfg.
Drugs of abuse increase serum- and glucocorticoid-inducible kinase 1 expression in the ventral tegmental area (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7915;
We found that repeated injections of morphine or cocaine increase the expression of serum- and glucocorticoid- inducible kinase 1 (SGK1) in the VTA using RNA sequencing...To assess whether SGK1 expression is occurring in specific neuronal populations or non-neuronal cells such as glia we are utilizing RNAScope analysis. Together, these studies will define how drugs of abuse alter expression of SGK1 in the VTA, a necessary first step to explore the role of this gene in drug behavior.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Transcriptional effects of fentanyl versus morphine exposure and withdrawal in reward-associated regions of the brain (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7791;
Data from bulk mRNA sequencing of the nucleus accumbens (NAc) and ventral tegmental area (VTA) were analyzed to reveal the transcriptional changes resulting from exposure to and withdrawal from fentanyl compared to morphine and a saline control group. Our findings indicate that synthetic opioids exert some unique transcriptional effects on these brain reward regions and suggest further epigenetic investigations to uncover the mechanisms behind these differences.
- |||||||||| morphine sulphate / Generic mfg.
Acute morphine and glucocorticoid signaling regulate heat shock gene expression in astrocytes (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7789;
These findings suggest GR, not mu opioid receptor, activation is both sufficient and necessary to induce FKBP5 expression in astrocytes. We are currently working on validation of a CRISPR interference (CRISPRi) tool for selective repression of NR3C1, which encodes the GR, in astrocytes to further investigate how GR signaling mediates opioid-induced transcriptional responses.
- |||||||||| morphine sulphate / Generic mfg.
The role of striatal ?-opioid receptors in opioid-driven striatal dynamics and behavior (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7779;
We have also developed viral genetic approaches to determine whether ?OR expression in different striatal subregions is necessary and sufficient for morphine-induced dopamine release and/or conditioned place preference. By characterizing the cell-type-specific dynamics of an important, habit-associated brain region in opioid reinforcement, our experiments contribute to our basic knowledge of the neural substrates underlying the transition to compulsive opioid use.
- |||||||||| morphine sulphate / Generic mfg., clozapine / Generic mfg.
Characterization of ventral tegmental area neuromedin-s expressing neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7775;
We have found that neuromedin S (NMS) gene expression is increased by chronic morphine in VTA DA neurons...To investigate this, we injected Cre-dependent excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) into the VTA of NMS-Cre mice and administered clozapine-n-oxide (CNO) to activate VTA-NMS neurons...Our initial studies indicate that VTA-NMS neurons project to the nucleus accumbens and lateral hypothalamus, but not the prefrontal cortex. Taken together, these studies suggest that VTA-NMS neurons represent a subset of DA neurons, and that VTA-NMS circuitry may represent a novel target for intervention for OUD.
- |||||||||| morphine sulphate / Generic mfg.
Small Molecule Therapeutics for Opioid Addiction (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7774;
The goal of the present study was to evaluate the effects of D-CYSee and betaine on redox homeostasis and DNA methylation levels during morphine (MOR) treatment...In conclusion, D-CYSee and betaine reduces cellular stress and prevents abnormal methylation patterns observed in cultured neurons. This shows that D-CYSee and betaine may be a potential treatment for opioid addiction.
- |||||||||| morphine sulphate / Generic mfg.
Opioid inhibition of neurons in the anterior paraventricular nucleus of the thalamus (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7769;
Taken together the results indicate that there are cell selective adaptive mechanisms that alter the activity of aPVT neurons following chronic morphine treatment. Receptor-dependent tolerance would contribute to dose escalation, while the increased excitability would contribute to signs of withdrawal.
- |||||||||| morphine sulphate / Generic mfg.
Cannabidiol inhibits c-Jun N-terminal Kinase (JNK) to block JNK-dependent reactive oxygen species production (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7767;
We predict that pSNL surgery will cause elevated phosphorylated JNK levels, and treatment of CBD through gelatin administration will inhibit this elevation. These data are consistent with the hypothesis that CBD directly inhibits JNK activity during pain states and morphine treatment, providing a mechanistic model for how CBD modulates both pain and opioid function.
- |||||||||| morphine sulphate / Generic mfg.
The Terpenes Beta-Caryophyllene and Alpha-Humulene are Aversive in a Conditioned Place Paradigm via Activation of Adenosine A2aReceptors in the Brain (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7760;
We then assessed the combination of the opioid drug morphine and BCP or ?-hum in the CP assay...We anticipate a decrease in dopamine release in terpene-treated mice.Our work suggests the terpene BCP acts via A2aR and when combined with opioid drugs, decreases opioid reward and enhances pain relief. Together, these findings expand our work on the pharmacological properties of terpenes and suggest that BCP could be an alternate non-opioid, non-cannabinoid therapy for treating neuropathic pain while mitigating opioid reward.
- |||||||||| fentanyl citrate / Generic mfg.
Environmental Enrichment Attenuates Fentanyl Use and Stress Induced Drug Seeking Behavior (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7644;
These findings suggest that EE can suppress maladaptive fentanyl use and stress induced relapse and reveal sex differences in stress reactivity associated with opioid use. Together, this work highlights the need to better understand individual vulnerabilities to stress during opioid use and points to the therapeutic potential of environmental factors influencing the effects of stress on opioid use.
- |||||||||| morphine sulphate / Generic mfg.
Epigenetic regulation in the medial prefrontal cortex underlying vulnerability to opioid addiction throughout its trajectory in male and female rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7301;
Here, we investigated genome-wide transcription (using RNA-seq) and chromatin accessibility (using ATAC-seq) in the medial prefrontal cortex of male and female rats in three paradigms modeling the initial response to passive, repeated morphine exposure (Withdrawal-Induced Anhedonia), persistent use (Demand), and relapse (Reinstatement)...In conclusion, we have identified changes in gene networks, upstream regulators, biological pathways, and TF binding motifs that are either phase-specific or span all three phases along the addiction trajectory. We have also identified a set of changes that covary with individual differences in addiction vulnerability and severity.
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