Extracellular matrix protein laminin β1 regulates pain sensitivity and anxiodepression-like behaviors in mice

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one alpha-, one beta-, and one was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity interaction with integrin beta 1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin beta 1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

Automated summary

Patients with neuropathic pain often have comorbid psychiatric disorders. The study revealed that LAMB1 in the ECM plays a crucial role in modulating pain plasticity through signal transduction pathways, highlighting a potential therapeutic target for neuropathic pain treatment.