Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter - PubMed (original) (raw)

Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter

Xing-Jun Liu et al. Cell Res. 2014 Nov.

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Figure 1

Figure 1

MyD88 in nociceptive neurons is essential for driving innate and adaptive immunity in DRGs and maintaining neuropathic pain following chemotherapy. (A) FACS analysis showing the overall populations of leukocytes (CD45+) in DRGs of WT and CKO mice with and without PTX treatment (7 d). (B) Quantification of CD45+ leukocytes in DRGs with fold changes (vs. WT-control). (C) Fold changes of monocytes (CD11b+CD14+ and CD11b+Gr-1medium), macrophages (CD11b+), and neutrophils (CD11b+Gr-1high) in DRGs of WT and CKO mice with and without PTX treatment (7 d). **P< 0.01, ***P< 0.001, compared with WT; #P< 0.05, ##P< 0.01, compared with WT + PTX; n = 7-10 mice/group in B-C. (D) Fold changes of T lymphocytes (CD3+), helper T cells (CD4+), cytotoxic T cells (CD8+), and antigen presenting cells (IA/IE+) in DRGs of WT and CKO mice with and without PTX treatment (7 d). **P< 0.01, ***P< 0.001, compared with WT; #P< 0.05, ###P< 0.001, compared with WT + PTX; n = 6-9 mice/group. (E) Time course of PTX-induced neuropathic pain (mechanical hypersensitivity, 0.6 g filament) in WT and CKO mice. *P< 0.05, vs. WT; n = 5 mice/group. (F) Time course of MyD88 expression (western blot) in DRGs following PTX treatment. Lower panel, quantification of the intensity of MyD88 bands. *P< 0.05, vs. vehicle. n = 5 mice/group. (G) Blocking the function of CD8+ T cells with a neutralizing antibody via intrathecal injections (5 μg, once a day for 3 days) reduces PTX-induced mechanical allodynia (0.16 g filament). Arrows indicate antibody injections; n = 4-5 mice/group; *P< 0.05. (H) Adoptive transfer of CD8+ T cells or Tregs via intrathecal injections (2.5 × 105 cells in 10 μl) 3 days after PTX-treatment increases or decreases mechanical allodynia (0.16 g filament), respectively. *P< 0.05; n = 8 mice/group. (I) CFA-induced enlargement of affected lymph nodes (lymphadenopathy, 7 d after CFA injection) in WT and CKO mice. n = 4-5 mice/group; Scale, 5 mm; *P< 0.05. (J) Capsaicin-induced neurogenic inflammation, measured by Evans blue extravasation, in hindpaw tissues of WT and CKO mice. n = 5 mice/group; *P< 0.05; NS, no significance. Mechanical sensitivity was measured by frequency (%) of paw withdrawal response to a von Frey filament (0.6 or 0.16 g). All data are expressed as mean ± SEM.

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