Ağrının Moleküler Düzenlenmesinde Mikrorna’ların Rolü
Özet
Ağrı, zararlı uyaranlara ve doku hasarına yanıt olarak ortaya çıkan ve vücutta koruyucu bir rol oynayan nöronal sistemle ilişkili, çok yönlü ve karmaşık bir süreçtir ve bu nedenle kişinin yaşam kalitesini etkiler. Doku hasarı sonucunda, termal, mekanik veya kimyasal uyaranlar nosiseptörleri aktive ederek ağrı sinyallerinin beyne iletilmesine ve ağrı algısı ile ağrıya bağlı davranışsal tepkilere yol açar. MikroRNA'lar (miRNA'lar), epigenetik değişikliklerle karakterize edilen ağrı ilerlemesinin başlatılmasında ve sürdürülmesinde önemli bir rol oynar. miRNA'lar, DNA dizisini değiştirmeden tamamlayıcı eşleşme yoluyla gen ekspresyonunu transkripsiyonel ve transkripsiyon sonrası olarak düzenleyen kısa, kodlayıcı olmayan RNA molekülleridir. Sinir sisteminde yaygın olarak ifade edilen miRNA'lar, MAPK ve NF-κB gibi sinyal yolları, iyon kanalları, nöronal uyarılabilirlik, nöroinflamasyon, mikroglial aktivasyon, nöronal sağkalım ve rejenerasyon dahil olmak üzere temel ağrı mekanizmalarına katılarak ağrının patogenezine katkıda bulunur. Ağrı gelişiminin altında yatan nosiseptif süreçte, miRNA'ların inhibisyonu veya artmış ekspresyonu nöropatik ağrının seyrini etkiler. Ağrı sürecinde düzensizleşen miRNA'lar, klinik uygulamada terapötik hedefler ve biyobelirteçler olma potansiyeline sahiptir. Bu bölümde, ağrının fizyolojisi, miRNA biyogenezi ve işlevi ile miRNA'ların ağrı düzenlemesindeki rolleri ve klinik uygulamaları ele alınacaktır.
Pain is a multifaceted and complex process that arises in response to harmful stimuli and tissue damage and is associated with the neuronal system, which plays a protective role in the body, thereby affecting a person's quality of life. As a result of tissue damage, thermal, mechanical, or chemical stimuli activate nociceptors, leading to the transmission of pain signals to the brain and resulting in pain perception and pain-related behavioral responses. MicroRNAs (miRNAs) play an important role in the initiation and maintenance of pain progression, which is characterized by epigenetic changes. miRNAs are short non-coding RNA molecules that regulate gene expression transcriptionally and post-transcriptionally through complementary pairing without altering the DNA sequence. miRNAs, which are widely expressed in the nervous system, contribute to the pathogenesis of pain by participating in fundamental pain mechanisms, including signaling pathways such as MAPK and NF-κB, ion channels, neuronal excitability, neuroinflammation, microglial activation, neuronal survival, and regeneration. In the nociceptive process underlying pain development, the inhibition or increased expression of miRNAs affects the course of neuropathic pain. Dysregulated miRNAs during the pain process have the potential to be therapeutic targets and biomarkers in clinical practice. This chapter will discuss the physiology of pain, miRNA biogenesis and function, and the roles and clinical applications of miRNAs in pain regulation.
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