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Mechanistic insights into NLRP3 inflammasome regulation of chronic pain

YANG Zong-Zhi^1,2, WU Jie¹, HUANG Xiao-Lan¹, XIONG Dong-Lin³, LUO Yu-Hui³, XIAO Li-Zu³, FAN Bi-Fa⁴, JIANG Chang-Yu^1,3,*

¹First School of Clinical Medicine, Guangdong Medical University, Zhanjiang 524023, China；²Department of Anesthesiology, Heyuan Maternal and Child Health Hospital, Heyuan 517000, China；³Pain Department, Shenzhen Nanshan People's Hospital, Shenzhen 518052, China；⁴Pain Department, China-Japan Friendship Hospital, Beijing 100029, China

Abstract

The NLRP3 inflammasome, a pivotal effector of the innate immune system, has emerged as a critical regulator in the initiation and maintenance of chronic pain. Accumulating evidence demonstrates that NLRP3 inflammasome activation in the peripheral nervous system, particularly in dorsal root ganglia (DRG), promotes the release of pro-inflammatory mediators such as interleukin-1β (IL-1β), enhances sensory neuronal excitability, and facilitates nociceptive signal transmission and amplification. Moreover, satellite glial cells and infiltrating immune cells within the DRG contribute to the establishment of an inflammatory microenvironment, forming a neuron-glia-immune network that drives pain sensitization. In the central nervous system, activation of the NLRP3 inflammasome in microglia and astrocytes induces alterations in synaptic plasticity and central sensitization, further exacerbating the aberrant amplification of pain signals. This review summarizes recent advances in elucidating the regulatory mechanisms of the NLRP3 inflammasome in chronic pain in both peripheral and central nervous systems, providing a theoretical foundation for the development of novel analgesic strategies targeting the inflammasome.

Key words: NLRP3 inflammasome; chronic pain; mechanism; neuroinflammation; glial cells

Received: 　　Accepted:

Corresponding author: 蒋昌宇　　E-mail:

DOI: 10.13294/j.aps.2026.0009

Citing This Article：

YANG Zong-Zhi, WU Jie, HUANG Xiao-Lan, XIONG Dong-Lin, LUO Yu-Hui, XIAO Li-Zu, FAN Bi-Fa, JIANG Chang-Yu. Mechanistic insights into NLRP3 inflammasome regulation of chronic pain. Acta Physiol Sin 2026; 78 (1): 135-147 (in Chinese with English abstract).