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Updated: Apr 21, 2026
Author Spotlight: Microglia Research on Spinal Cord Heterogeneity and Purification
Published on: September 22, 2023
Scratching activates microglia in the mouse spinal cord
Ying Zhang1, Siok L Dun, Yi-Hung Chen
1Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania; Department of Pathophysiology, Kunming Medical University, Kunming, China.
Abstract:
This study tested the hypothesis that repetitive scratching provoked by two known pruritogens, compound 48/80 and 5'-guanidinonaltrindole (GNTI), is accompanied by activation of microglial cells in the mouse spinal cord. Immunohistochemical studies revealed that the complement receptor 3, also known as cluster determinant 11b (CD11b), a cell surface marker of microglial cells, was upregulated in the spinal cord 10-30 min after a subcutaneous (s.c.) injection of compound 48/80 (50 μg/100 μl) or GNTI (0.3 mg/kg) to the back of the mouse neck. Numerous intensely labeled CD11b-immunoreactive (CD11b-ir) cells, with the appearance of hypertrophic reactive microglia, were distributed throughout the gray and white matter. In contrast, weakly labeled CD11b-ir cells were distributed in the spinal cord from mice injected with saline. Western blots showed that CD11b expression levels were significantly increased in spinal cords of mice injected s.c. with either pruritogen, reached a peak response in about 30 min, and declined to about the basal level in the ensuing 60 min. In addition, phospho-p38 (p-p38) but not p38 levels were upregulated in spinal cords from mice injected with compound 48/80 or GNTI, with a time course parallel to that of CD11b expression. Pretreatment of the mice with nalfurafine (20 µg/kg; s.c.), a κ-opioid receptor agonist that has been shown to suppress scratching, reduced CD11b and p-p38 expression induced by either pruritogen. The results demonstrate, for the first time, that scratch behavior induced by the pruritogens GNTI and compound 48/80 is accompanied by a parallel activation of microglial cells in the spinal cord.
Insights
Scratching activates spinal cord microglia, indicated by increased CD11b expression, following pruritogen injection. This microglial activation, along with phospho-p38 upregulation, is reduced by nalfurafine, a κ-opioid receptor agonist.
Area of Science:
- Neuroscience
- Immunology
- Pruritogen Research
Background:
- Repetitive scratching is a common symptom of various skin conditions.
- The role of spinal cord microglial activation in itch-scratch behavior is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that scratching induced by pruritogens activates microglial cells in the mouse spinal cord.
- To examine the expression of microglial markers and associated signaling pathways during scratching behavior.
Main Methods:
- Immunohistochemistry was used to detect cluster determinant 11b (CD11b), a microglial marker, in mouse spinal cords.
- Western blotting was employed to quantify CD11b and phospho-p38 (p-p38) expression levels.
- Mice were injected with pruritogens (compound 48/80 or GNTI) or saline, with or without nalfurafine pretreatment.
Main Results:
- Subcutaneous injection of compound 48/80 or GNTI significantly upregulated CD11b expression in the spinal cord within 10-30 minutes, indicating microglial activation.
- Western blot analysis confirmed increased CD11b levels peaking at 30 minutes post-injection.
- Phospho-p38 (p-p38) levels also increased in parallel with CD11b, and nalfurafine pretreatment suppressed both CD11b and p-p38 upregulation.
Conclusions:
- Scratch behavior induced by compound 48/80 and GNTI is associated with parallel activation of spinal cord microglial cells.
- The findings suggest a role for microglial activation and p38 MAPK signaling in the spinal cord's response to pruritogens.
- Nalfurafine, a κ-opioid receptor agonist, effectively suppresses this pruritogen-induced microglial activation.
