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The Various Functions of Opioids in Pathophysiological Conditions

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Neural Functions of the Delta-Opioid Receptor

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Abstract

Opioids and their analogues have been used as clinical analgesics for several centuries, with reports dating back to as early as 4000 B.C. Their anti-pain action is primarily accomplished through three major opioid receptor subtypes: μ-opioid receptor (MOR), δ-opioid receptor (DOR), and κ-opioid receptor (KOR). Although these opioid receptors have been cloned in many species, their complex functions, other than pain modulation, are still largely unknown in both physiological and pathophysiological conditions. However, recent studies have uncovered fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Studies suggest that these opioid receptors participate in various physiological activities. Therefore, their dysfunction may play a role in numerous diseases, including hypoxic/ischemic injury in brain, epileptic seizures, Parkinson’s disease, Multiple Sclerosis, cardiovascular disease, respiratory depression, pulmonary artery hypertension, malignancies, diabetic cutaneous wounds, immune disease, chronic kidney disease, uremic pruritus, renal ischemia-reperfusion injury, and pre-eclampsia. There is also strong evidence showing that opioid receptors are involved in the regulation of stress, feeding and obesity, and play an essential role in hibernation in some species. One of the most exciting findings in the past decade is DOR-mediated neuroprotection and cardioprotection. The upregulation of DOR expression and activity increases the neuronal and myocardial tolerance to hypoxic and/or ischemic stress. The DOR signal triggers different mechanisms at multiple levels, depending on stress duration and severity, to preserve neuronal and myocardial survival, including the stabilization of homeostasis and increase in pro-survival signaling. DOR-mediated neuroprotection and cardioprotection may potentially influence clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this chapter is to update recent research on opioids and their various functions, particularly in pathophysiological conditions. This chapter aims to deliver an informative reference for better understanding the opioid system from a/the pathophysiological point of view.

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Abbreviations

AHR:

Airway hyperresponsiveness

BMDCs:

Bone marrow dendritic cells

BNTX:

7-Benzylidenenaltrexone

BUN:

Blood urea nitrogen

CKD-aP:

Chronic kidney disease-associated pruritus

DG:

Dentate gyrus

DOR:

δ-Opioid receptor

EMT:

Epithelial mesenchymal transition

GBM:

Glioblastoma

HCC:

Hepatocellular carcinoma

IRI:

Renal ischaemia-reperfusion

KO:

Knockout

KOR:

κ-Opioid receptor

L-NAME:

N-nitro-L-arginine methyl ester

LPS:

Lipopolysaccharide

MS:

Multiple Sclerosis

MOR:

μ-Opioid receptor

NB:

Neuroblastoma

NPC:

Neural progenitor cells

NTX:

Naltrexone

OGF:

Opioid growth factor

ORL:

Opioid receptor-like orphan receptor

PAH:

Pulmonary artery hypertension

PASMCs:

Pulmonary arterial smooth muscle cells

PD:

Parkinson’s disease

PDYN:

Pro-dynorphin

PENK:

Pro-enkephalin

RIPC:

Remote ischaemic preconditioning

PIS:

Penicillin-induced seizures

PKC:

Protein kinase C

POMC:

Pro-opiomelanocortin

RR-EAE:

Relapse-remitting experimental autoimmune encephalomyelitis

RUPP:

Uteroplacental perfusion

TK:

Tyrosine kinase

WT:

Wild-type

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Acknowledgements

The work was supported by NIH (HD-034852 and AT-004422) and Vivian L Smith Neurologic Foundation. GW and TC were supported by the National Natural Science Foundation of China (81260204; 81060096).

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Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, 77030, USA

    Huimin Gao M.D., Ph.D, Dongman Chao Ph.D, Sebastian J. Villarreal M.D, Daniel Yiu B.A, Tao Chen M.D., Ph.D, Yong Xia M.D., Ph.D & Fei Yao M.D., Ph.D

  2. Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Guangzhou, Guangdong, 510060, China

    Huimin Gao M.D., Ph.D & Qing Wang M.D., Ph.D

  3. University of Texas Medical School, Houston, TX, USA

    Ying Xia M.D., Ph.D

  4. Department of Neurology, Hainan General Hospital, Haikou, Hainan, 570311, China

    Guoqiang Wen M.D & Tao Chen M.D., Ph.D

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    Ying Xia

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Gao, H. et al. (2015). The Various Functions of Opioids in Pathophysiological Conditions. In: Xia, Y. (eds) Neural Functions of the Delta-Opioid Receptor. Springer, Cham. https://doi.org/10.1007/978-3-319-25495-1_18

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