Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson's Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560700PMC
http://dx.doi.org/10.12659/msm.883259DOI Listing

Publication Analysis

Top Keywords

endogenous morphine
20
parkinson's disease
8
morphine expression
8
endogenous
5
morphine
5
disease l-dopa
4
l-dopa endogenous
4
morphine revisit
4
revisit clinical
4
clinical observations
4

Similar Publications

Background: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background.

View Article and Find Full Text PDF

Structure-Activity Relationships and Molecular Pharmacology of Positive Allosteric Modulators of the Mu-Opioid Receptor.

ACS Chem Neurosci

January 2025

Edward F Domino Research Center, Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States.

Positive allosteric modulation of the mu-opioid receptor is a promising strategy to address the ever-growing problem of acute and chronic pain management. Positive allosteric modulators (PAMs) of the mu-opioid receptor could be employed to enhance the efficacy of endogenous opioid peptides to a degree that provides pain relief without the need for traditional opioid drugs. Alternatively, PAMs might be used to enhance the action of opioid drugs and so provide an opioid-sparing effect, allowing for the use of lower doses of opioid agonists and potentially decreasing associated side effects.

View Article and Find Full Text PDF

The dual modulating effects of neuropeptide FF on morphine-induced analgesia at the spinal level.

Neuroscience

December 2024

Institute of Physiology, School of Basic Medical Sciences, and State Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address:

Increasing evidence indicates that neuropeptide FF (NPFF) produces analgesic effects and augments opioid-induced analgesia at the spinal level. However, our recent research demonstrated that NPFF exerted complex opioid-modulating effects in an inflammatory pain model after intrathecal (i.t.

View Article and Find Full Text PDF

Positive allosteric modulation of µ-opioid receptor - A new possible approach in the pain management?

Biochem Pharmacol

November 2024

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address:

The antinociceptive effect of the opioid drugs is achieved through activation of the µ-opioid receptor (MOP). The orthosteric and allosteric sites of opioid receptors may be modulated, orthosteric site by endogenous i.e.

View Article and Find Full Text PDF

Distinguishing the brain mechanisms affected by distinct addictive drugs may inform targeted therapies against specific substance use disorders (SUDs). Here, we explore the function of a drug-associated, transcriptionally repressive transcription factor (TF), ZFP189, whose expression in the nucleus accumbens (NAc) facilitates cocaine-induced molecular and behavioral adaptations. To uncover the necessity of ZFP189-mediated transcriptional control in driving cocaine-induced behaviors, we created synthetic ZFP189 TFs of distinct transcriptional function, including ZFP189, which activates the expression of target genes and exerts opposite transcriptional control to the endogenously repressive ZFP189.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!