Can We Treat Chronic Pain by Targeting Neuroinflammation?

Chronic pain management constitutes a considerable unmet medical challenge. Existing treatments for chronic pain are either ineffective or result in undesirable side effects such as development of addiction. The discovery of novel non-opioid analgesic drugs is a highly desirable but also exceptionally challenging endeavor. One significant issue in developing new therapies is the translational gap between preclinical animal models and clinical outcomes. To address these issues and create effective pain treatments, it is necessary to understand the cellular mechanisms and molecular pathways that initiate and maintain chronic pain. In this presentation, I will describe the neuronal circuits responsible for pain perception. We will explore the interactions between neurons and non-neuronal cells in both acute and chronic pain contexts, with a particular focus on neuroimmune interactions in osteoarthritis pain. We will critically evaluate current in vitro models based on primary neuronal and organotypic cultures, which provide relatively rapid assessments of new drug candidates' effects on neuronal survival, morphology, activity, and interactions with other cells. Additionally, I will discuss recent progress in the development, behavioral characterization, and pharmacological validation of in vivo rodent models of osteoarthritis and inflammatory pain. By analyzing several examples of pain drug development programs, we will address the challenges of translating preclinical results into clinically successful drugs and summarize strategies to enhance the quality and efficiency of chronic pain drug development.

Learning Objectives:

1. Define pain neuronal circuitry and the role of non-neuronal cells in pain sensation.

2. Examine pros and cons of preclinical pain models.

3. Outline methods to enhance the translatability of chronic pain models.