TY - JOUR
T1 - B-cell and plasma cell activation in a mouse model of chronic muscle pain
AU - Lenert, Melissa E.
AU - Green, Audrey R.
AU - Merriwether, Ericka N.
AU - Burton, Michael D.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Fibromyalgia (FM) is a complex chronic musculoskeletal pain disorder with an elusive pathogenesis, with a strong implication of immune interactions. We recently found that IL-5 and the adaptive immune system mediates pain outcomes in fibromyalgia (FM) patients and preclinical models of FM-like chronic widespread pain (CWP). However, there is an active debate if FM/CWP has an autoimmune etiology. Preclinical models of CWP utilize a repeated insult paradigm, which resembles a primary, then secondary response similarly observed in the antibody response, in which the subsequent event causes a potentiated pain response. Recent translational studies have implicated immunoglobulins (Ig) and B-cells in FM/CWP pathophysiology. To understand if these are involved in preclinical models of CWP, we performed comprehensive B-cell phenotyping in the bone marrow, circulation, and popliteal (draining) lymph nodes in the two-hit acidic saline model of CWP. We found increased MHC class II-expressing B-cells in peripheral blood, increased activated plasma cells in peripheral blood, and increased memory B-cells in the bone marrow. Interestingly, acidic pH (4.0) injected mice have reduced levels of IgG1, independent of treatment with IL-5. We have demonstrated that the acidic saline model of CWP induces T-cell mediated activation of B-cells, increased active plasma cells, and increased memory B-cells in female mice.
AB - Fibromyalgia (FM) is a complex chronic musculoskeletal pain disorder with an elusive pathogenesis, with a strong implication of immune interactions. We recently found that IL-5 and the adaptive immune system mediates pain outcomes in fibromyalgia (FM) patients and preclinical models of FM-like chronic widespread pain (CWP). However, there is an active debate if FM/CWP has an autoimmune etiology. Preclinical models of CWP utilize a repeated insult paradigm, which resembles a primary, then secondary response similarly observed in the antibody response, in which the subsequent event causes a potentiated pain response. Recent translational studies have implicated immunoglobulins (Ig) and B-cells in FM/CWP pathophysiology. To understand if these are involved in preclinical models of CWP, we performed comprehensive B-cell phenotyping in the bone marrow, circulation, and popliteal (draining) lymph nodes in the two-hit acidic saline model of CWP. We found increased MHC class II-expressing B-cells in peripheral blood, increased activated plasma cells in peripheral blood, and increased memory B-cells in the bone marrow. Interestingly, acidic pH (4.0) injected mice have reduced levels of IgG1, independent of treatment with IL-5. We have demonstrated that the acidic saline model of CWP induces T-cell mediated activation of B-cells, increased active plasma cells, and increased memory B-cells in female mice.
KW - Autoimmune
KW - B-cell
KW - Female
KW - Fibromyalgia
KW - Musculoskeletal pain
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U2 - 10.1016/j.ynpai.2024.100169
DO - 10.1016/j.ynpai.2024.100169
M3 - Article
AN - SCOPUS:85207038326
SN - 2452-073X
VL - 16
JO - Neurobiology of Pain
JF - Neurobiology of Pain
M1 - 100169
ER -