Single-Cell Dynamics in Pain Resolution

The primary goal of this project is to investigate the molecular and cellular mechanisms involved in natural pain resolution. Specifically, the project seeks to identify subtypes of local macrophages and satellite glial cells (SGC) that play a crucial role in pain resolution following nerve injury. By studying these cell types in both animal models and human patients, we aim to better understand how the healing process unfolds at the cellular level and how macrophages and SGCs interact to mediate pain resolution.

Background

Neuropathic pain, often caused by nerve injury, can lead to long-lasting pain in some patients. However, pain resolution occurs naturally in some cases, although the mechanisms behind this process are not fully understood. Previous research has identified the role of sensory neurons, glial cells, and macrophages in the progression of neuropathic pain. However, little is known about how these cells contribute to the resolution of pain. In particular, macrophages at the neuron-glial interface have shown a significant role in modulating pain responses. Additionally, there is a potential connection between the macrophages in the dorsal root ganglion (DRG) and blood monocytes/macrophages, which could provide insights into chronic pain syndromes like Chronic Regional Pain Syndrome (CRPS).

Research Objective

We aim to:

• Identify the cellular phenotypes of local macrophages and SGCs in the DRG that produce critical signaling mediators during pain resolution.
• Investigate the transcriptional reprogramming of SGCs and DRG macrophages during pain resolution, with a focus on differences between sexes.
• Isolate and categorize blood monocyte subtypes from rats with neuropathic pain and CRPS patients, correlating them with macrophage phenotypes in the DRG.
• Model the multicellular mechanisms of pain resolution by studying the dynamic interactions between macrophages, sensory neurons, and SGCs in a 3D cell culture system.

Significance

This research will provide valuable insights into the molecular and cellular processes that facilitate pain resolution. Understanding the role of macrophages and SGCs in pain resolution will not only enhance our understanding of the biological mechanisms behind neuropathic pain but could also identify novel therapeutic targets for chronic pain conditions, such as CRPS. The comparison of neuropathic pain in rats with induced pain and human CRPS patients will bridge the gap between basic science and clinical applications, offering a pathway for improving treatment strategies for those suffering from chronic pain.