Role of mitochondrial Ca2+ uniporter in remifentanil-induced postoperative allodynia. 2018

Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No.253 Gongye Ave, Guangzhou, Guangdong, China.

Opioid-induced hyperalgesia (OIH) and allodynia is a well-known phenomenon and refers to the pain sensitization in patients after prolonged opioid exposure. OIH limits the use of opioids in pain control, but the underlying mechanisms are not fully clear. This study investigated the role of mitochondrial Ca2+ uniporter (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. Using a rat model of OIH, we found that incision- and remifentanil-induced mechanical allodynia were remarkably attenuated by pretreatment with Ru360, a specific MCU antagonist, suggesting a critical role of MCU in both incision- and opioid-induced allodynia. In addition, imaging studies with Rhod-2 (a mitochondrial Ca2+ dye) in spinal tissues demonstrated increased mitochondrial Ca2+ level in response to incision and remifentanil infusion, which was attenuated by Ru360. Western blot and immunohistochemistry showed that pNR [phosphorylated N-methyl-D-aspartate (NMDA) receptor] and pERK (phosphorylated extracellular signal-regulated kinase) are increased during both incision-induced hyperalgesia and remifentanil-induced hyperalgesia, and again the increases in pNR and pERK were remarkably attenuated by Ru360. Together, our data demonstrate that MCU plays a critical role in remifentanil-induced postoperative mechanical allodynia, with NMDA receptor and ERK as possible downstream effectors. Our findings provide novel mechanisms for remifentanil-induced mechanical allodynia and encourage future studies to examine the mitochondrial Ca2+ uniporter as a potential therapeutic target for prevention of OIH.

UI MeSH Term Description Entries
D008297 Male Males
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010880 Piperidines A family of hexahydropyridines.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006930 Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia, Tactile,Hyperalgesia, Thermal,Hyperalgia,Hyperalgia, Mechanical,Hyperalgia, Primary,Hyperalgia, Secondary,Allodynia,Allodynia, Mechanical,Allodynia, Tactile,Allodynia, Thermal,Hyperalgesia, Mechanical,Hyperalgesia, Primary,Hyperalgesia, Secondary,Hyperalgesic Sensations,Mechanical Allodynia,Mechanical Hyperalgesia,Tactile Allodynia,Thermal Allodynia,Allodynias,Hyperalgesias,Hyperalgesias, Thermal,Hyperalgesic Sensation,Mechanical Hyperalgia,Mechanical Hyperalgias,Primary Hyperalgia,Primary Hyperalgias,Secondary Hyperalgia,Secondary Hyperalgias,Sensation, Hyperalgesic,Sensations, Hyperalgesic,Thermal Hyperalgesia
D000077208 Remifentanil A piperidine-propionate derivative and opioid analgesic structurally related to FENTANYL. It functions as a short-acting MU OPIOID RECEPTOR agonist, and is used as an analgesic during induction or maintenance of general anesthesia, following surgery, during childbirth, and in mechanically ventilated patients under intensive care. 3-(4-Methoxycarbonyl-4-((1-oxopropyl)phenylamino)-1-piperidine)propanoic Acid Methyl Ester,GI 87084B,GI-87084B,GI87084B,Remifentanil Hydrochloride,Remifentanil Monohydrochloride,Ultiva
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013116 Spinal Cord A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER. Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords

Related Publications

Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
September 2014, Nature,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
January 2017, Handbook of experimental pharmacology,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
April 2019, Journal of cellular and molecular medicine,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
April 2023, Acta physiologica (Oxford, England),
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
May 2006, Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
June 2020, Nature,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
January 2019, Cell reports,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
April 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
January 2017, Cell death discovery,
Aizhu Lu, and Hongyi Lei, and Le Li, and Luying Lai, and Wenbin Liang, and Shiyuan Xu
February 2022, The Journal of biological chemistry,
Copied contents to your clipboard!