ReviewAction of β-endorphin and nonsteroidal anti-inflammatory drugs, and the possible effects of nonsteroidal anti-inflammatory drugs on β-endorphin
Introduction
Endogenous opioid peptide is a general term for peptides that are naturally produced in the mammalian body with opioid-like effects. Their main function is to exert an analgesic effect by participating in the regulation of information, such as inhibition of the transfer of pain information [1], [2]. They act on three main opioid receptors, including μ(MOR), δ(DOR), and κ(KOR) opioid receptors, which were found in the brain of mammals in 1973, but their impacts extend to act on cytokine receptors and exert partially ambiguous pharmacological effects [3].
In the family of opioid peptides, β-endorphin, which exists in hypothalamus, hypophysis cerebri, cerebral cortex, amygdala, gyri hippocampi, brainstem, cerebrospinal fluid, septal area, and plasma, is one of the most prominent endogenous peptides. The highest amount of β-endorphin is found in the hypophysis cerebri and hypothalamus [4], [5]. β-Endorphin is derived from pro-opiomelanocortin (POMC) in the cytoplasm, and developed from 31 amino acid residues in the C-terminal region of POMC which are then processed by enzymes [6], [7]. The affinity of β-endorphin for MOR and DOR is strong, and its main function is to produce an antinociceptive or analgesic effect on the receptors [5], [8].
Nonsteroidal anti-inflammatory drugs (NSAIDs), which are one of the most prescribed drugs nowadays, have anti-inflammatory, antipyretic, analgesic, and anti-rheumatic effects. They exert their effects by inhibiting cyclooxygenase (COX), thereby stopping the transformation of arachidonic acid into prostaglandins (PGs), thromboxane (TXA2) and prostacyclin I2 (PGI2) [39]. However, the traditional view that the effects of NSAIDs are mediated exclusively through a peripheral mechanism related to the inhibition of prostaglandin synthesis, as mentioned earlier, has been challenged. So we aimed to review research on the actions of β-endorphin and nonsteroidal anti-inflammatory drugs (NSAIDs) and the effects of NSAIDs on β-endorphin.
Section snippets
Mechanism of action of β-endorphin in analgesia
Endogenous opioid peptides regulate the pain information, which is transmitted from the periphery to the center, mainly through three mechanisms. Firstly, pain information can be transmitted through GABAergic neuron in the spinal cord in inferior central nervous system (CNS) [9], [91]. Then in superior CNS, the information can be transmitted in brain and can be projected from the supraspinal cord neurons to spinal cord neurons [92], [93]. Thirdly, the conduction of pain information can be
Mechanism of action of nonsteroidal anti-inflammatory drugs
At least three main COX isozymes have been found: COX-1, COX-2, and COX-3. COX-3 is expressed mainly in the brain cortex and heart [40]. COX-1 exists in normal cells, is produced under normal conditions, and is a constitutive protein of normal cells. It plays an important role in maintaining cellular homeostasis during the production of prostaglandins, such as maintaining the relative stability of renal blood flow, and has a protective function, such as the production of gastric mucus [41].
Effect of nonsteroidal anti-inflammatory drugs on β-endorphin (Fig. 2)
Studies found that the prophylactic administration of flurbiprofen axetil during the perioperative period or 30 min before the end of operation could effectively enhance the level of β-endorphin in the plasma of patients; however, the level significantly decreased in the control group [64], [65], [66]. An animal study found that in the formalin-induced inflammatory pain model, lornoxicam exerted an analgesic effect by reducing the content of nitric oxide (NO) and increasing the content of
Concluding remarks
It is well known that large doses of opioid drugs chronically can lead to the increase in sensitivity to pain, resulting in resistance to opioid drugs [82]. Research has shown that the increased release of PGE2 leads to the development of hyperalgesia [83]. An animal experiment has shown that the level of PGE2 in the cerebrospinal fluid increases five times in hyperalgesia. Hyperalgesia can be conspicuously inhibited by injecting the nonselective COX inhibitor naproxen intrathecally [84].
Funding sources
This study was supported by the Nation Natural Science Foundation of China (No. 81503080), the Anhui Provincial Natural Science Foundation (No. 1408085MH187, No. 1608085QH210)
Conflict of interest
The authors declare that they do not have any possible conflicts of interest.
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