Intrathecal injection in MaFIA mouse model inflicts localized reduction of macrophage populations within the dorsal root ganglia

Macrophages represent an essential component of the innate immune system that regulates multiple nervous system functions. This is highlighted in previous research that identifies an important somatosensory role for macrophages in peripheral dorsal root ganglia (DRG). In several pre-clinical pain models, DRG macrophage numbers increase with little evidence as to the origin. The objective of this work was to investigate this phenomenon with the innovative Macrophage Fas-Induced Apoptosis (MaFIA) mouse transgenic animal model and establish the source of macrophage expansion in a chronic intermittent hypoxia model. Intrathecal administration of AP20187 was performed in MaFIA mice to take advantage of the blood brain barrier impermeability of AP20187 and prevent exposure to systemic tissues in order to determine whether knocking down DRG tissue resident macrophages would alter hypoxia-related doubling of cell numbers in DRG. Localized AP20187 exposure to the central nervous system and adjacent DRG structures reduced macrophage in restricted neuronal tissues including spinal column and DRG without affecting macrophage populations in bone marrow, circulating blood, and sciatic nerve. Furthermore, MaFIA mice treated with AP20187 produced no increase in DRG macrophage cell numbers following exposure to chronic intermittent hypoxia. These findings indicate that targeted intrathecal administration of AP20187 reduces DRG tissue-resident macrophages and prevents chronic intermittent hypoxia-induced expansion of the innate immune cell population, negating a role for circulating monocytes in the phenomenon.