NLRP2 Is Overexpressed in Spinal Astrocytes at the Peak of Mechanical Pain Sensitivity during Complete Freund Adjuvant-Induced Persistent Pain

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 11408
• Main Authors: Ducza, László, Szücs, Péter, Hegedűs, Krisztina, Bakk, Erzsébet, Gajtkó, Andrea, Wéber, Ildikó, Holló, Krisztina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.10.2021; MDPI
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis Regulatory Proteins - metabolism; astrocyte; Astrocytes; Astrocytes - metabolism; Astrocytes - physiology; Attenuation; CFA-induced pain; Cytokines; Dorsal horn; Freund's Adjuvant - pharmacology; Gene Expression - genetics; Glial fibrillary acidic protein; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; IL-1β; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation - metabolism; Interleukin 1; Interleukin 1 receptors; Interleukin-1beta - metabolism; interleukin-1β; Ligands; Localization; Male; Nervous system; Neurons; Neurons - metabolism; NLRP2; Pain; Pain - metabolism; Pain - physiopathology; Pain perception; Pain sensitivity; Pain Threshold - physiology; persistent pain; Rats; Rats, Inbred WKY; Receptors, Interleukin-1 Type I - metabolism; Spinal cord; Spinal Cord - metabolism; Spinal Cord Dorsal Horn - metabolism; Tumor necrosis factor-TNF; NLRP2; CFA-induced pain; spinal cord; astrocyte; interleukin-1β; persistent pain
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111408

Our earlier findings revealed that interleukin-1 receptor type-1 (IL-1R1) was overexpressed in spinal neurons, and IL-1R1-deficient mice showed significant attenuation of thermal and mechanical allodynia during the course of the Complete Freund adjuvant (CFA)-induced persistent pain model. In the present study, we found that a ligand of IL-1R1, termed interleukin-1β (IL-1β), is also significantly overexpressed at the peak of mechanical pain sensitivity in the CFA-evoked pain model. Analysis of cellular distribution and modeling using IMARIS software showed that in the lumbar spinal dorsal horn, IL-1β is significantly elevated by astrocytic expression. Maturation of IL-1β to its active form is facilitated by the formation of the multiprotein complex called inflammasome; thus, we tested the expression of NOD-like receptor proteins (NLRPs) in astrocytes. At the peak of mechanical allodynia, we found expression of the NLRP2 inflammasome sensor and its significantly elevated co-localization with the GFAP astrocytic marker, while NLRP3 was moderately present and NLRP1 showed total segregation from the astrocytic profiles. Our results indicate that peripheral CFA injection induces NLRP2 inflammasome and IL-1β expression in spinal astrocytes. The release of mature IL-1β can contribute to the maintenance of persistent pain by acting on its neuronally expressed receptor, which can lead to altered neuronal excitability.