Hücre Sinyalizasyonunun Ağrıdaki Rolleri
Özet
Dünyada sürekli artış gösteren ağrı, hem bireylerin hayat konforunu bozmakta, hem de ülkelere ekonomik yük oluşturmaktadır. Ağrı, canlıların tehlikeli durumlardan kaçmalarını sağlayan ve hayatta kalmak için yakın çevrelerindeki zararlı uyaranları algılamaya yönelik bir savunma mekanizmasıdır. Ancak ağrı canlı için bir kâbusa dönüşebilmektedir ve ağrının yönetimi ve kontrolüne ihtiyaç duyulmaktadır. Günümüzde steroid olmayan antiinflamatuar ilaçlar ve opioidler gibi yaygın analjezik ilaçların uzun süreli kullanımının yan etkilere sahip olması ve devamında da ilaç bağımlılığının ortaya çıkması nedeniyle bu problemin çözümü için hedefe yönelik uygulamalar için moleküler düzeyde araştırmalar yapılmasını zorunlu kılmaktadır. Ağrı yönetimi için ağrı oluşumunda etkili olan hücre sinyallemesi, sinyalin oluşumunu sağlayan genetik faktörler gibi hücre içerisindeki moleküler hedeflere yönelik araştırmalarla yeni ağrı önleyici ilaçların keşfine de ihtiyaç duyulmaktadır. Bu bölümde ağrı oluşumu ve kontrolünde etkili olan moleküler hücre sinyal yolakları ele alınmış olup, birkaç yolak ve ağrı ile olan ilişkilerine vurgu yaparak bundan sonra odaklanılması gereken yolaklar mercek altına alınmıştır. Ağrıya neden olan faktörlerle karşılaşıldığında, nöron hücre zarlarında bulunan G protein reseptörleri aracığı ile sinyal algılandıktan sonra MAPK yolu, hedgehog (kirpi) sinyal yolu JAK/STAT yolu ya da PI3K-AKT yolu aracılığı ile sinyal hücre içine aktarılıp, hücre çekirdeğinde ilgili genler aktive edilerek ağrı duygusunu artıran ya da azaltan proteinlerin sentezlenmesi ve salgılanması ile ağrı duygusu ya yoğun olarak hissedilir ya da azalır. İşte bu yolakları kontrol eden yeni aday moleküllerin ağrı ile mücadelede etkili olabileceği tahmin edilmektedir.
Pain, which is constantly increasing worldwide, both impairs the quality of life of individuals and creates an economic burden for countries. Pain is a defense mechanism that allows living beings to escape from dangerous situations and to perceive harmful stimuli in their immediate environment in order to survive. However, pain can turn into a nightmare for the living being, and there is a need for pain management and control. Today, the long-term use of common analgesic drugs such as nonsteroidal anti-inflammatory drugs and opioids has side effects and leads to drug dependence, making molecular-level research for targeted applications necessary to solve this problem. For pain management, research into molecular targets within cells, such as cell signaling and genetic factors that enable signal generation, which are effective in pain formation, is needed to discover new pain-relieving drugs. This section discusses molecular cell signaling pathways that are effective in pain formation and control, highlighting several pathways and their relationships with pain, and focusing on the pathways that should be addressed in the future. When exposed to pain-causing factors, a signal is detected via G protein receptors located on the neuron cell membranes. This signal is then transmitted into the cell via the MAPK pathway, the hedgehog pathway, the JAK/STAT pathway, or the PI3K-AKT pathway. In the cell nucleus, the relevant genes are activated, leading to the synthesis and release of proteins that either increase or decrease the sensation of pain. As a result, the pain sensation is either intensified or reduced. It is predicted that new candidate molecules controlling these pathways may be effective in combating pain.
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