Battling pain from osteoarthritis: causing novel cell death

Abstract

Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.

1. Introduction

The prevalence of osteoarthritis (OA) may increase due to increasing average life expectancy and the world's population. OA is often accompanied by pain, which negatively affects a patient's physical function, quality of life and economic status. OA is a prevalent long-term condition affecting joints and is characterized by pain, swelling and restricted movement. OA damage is extensive and involves various parts of the joint. Painful joint alterations, such as synovitis and myelopathy, are related to abnormal cytokine expression or increased sensitivity to pain stimuli [1,2]. Pain is the most prevalent symptom and leading cause of disability in OA patients. Similarly, OA-related pain involves various inflammatory cytokines, structural joint changes, and neuropathic pain [3].

OA pain relief involves multiple mechanisms, and targeting inflammation and neuroinflammation; modulating specific signaling pathways; and inhibiting pyroptosis, ferroptosis, and necroptosis may be effective ways to reduce OA pain. Inflammation is an important factor in the development of OA pain, and neuroinflammation, in particular, plays a significant role in the development of OA pain. The development of pyroptosis, ferroptosis and necroptosis is associated with inflammatory responses, and inflammatory cytokines are a common cause of pain.

Notably, the development of pain caused by OA is similar to that caused by other types of pain. As a result, several medications, such as non-steroidal anti-inflammatory drugs and opioids, have been developed for treating pain. However, these drugs cannot provide adequate pain relief and have severe side effects, such as gastrointestinal harm, addiction, and hindrance in bone healing and remodeling [4‒6]. Although surgery can be used to treat OA, it can also cause more pain in the short term than the original disease can and even increase the risk of postoperative complications and chronic pain. Therefore, drugs with better efficacy and fewer side effects are needed to relieve pain and slow disease progression [7,8].