Microglia are involved in pruritus induced by DNFB via the CX3CR1/p38 MAPK pathway
1Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Background/Aims:
Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of neuropathic pain resulting from nerve injury or insult. Previous studies have shown the involvement of spinal microglia in the development of neuropathic pain, but their role in chronic pruritus is unclear.
Methods:
For this study, we constructed a model of chronic pruritus in mice using repeated applications of 2, 4-dinitrofluorobenzene (DNFB) and showed prolonged scratching behavior in treated mice that continued for at least 7 d after the final DNFB treatment.
Results:
Scratching was accompanied by activation of spinal microglia and both were reduced by an inhibitor of microglial activity. We also showed that microglial activation entailed increased signaling in the p38 MAPK pathway, and treatment with a p38 inhibitor reduced scratching in DNFB-treated mice. We also examined the role of fractalkine/CX3CR1 signaling in the development of DNFB-induced pruritus and showed that intrathecal administration of antiserum against either CX3CR1or FKN inhibited p38 activity and decreased scratching.
Conclusion:
Our results suggest that microglia are involved in pruritus induced by DNFB via FKN/CX3CR1/p38MAPK pathways similar to those participating in the development of neuropathic pain.
Insights
Spinal microglia contribute to chronic itch by activating the fractalkine/CX3CR1/p38 MAPK pathway. Inhibiting this pathway reduces scratching behavior in a mouse model of pruritus.
Area of Science:
- Neuroscience
- Immunology
Background:
- Chronic itch (pruritus) is a debilitating condition often linked to neuropathic pain.
- The role of spinal microglia in chronic itch remains poorly understood, unlike their established role in neuropathic pain.
Purpose of the Study:
- To investigate the involvement of spinal microglia in a mouse model of chronic pruritus.
- To elucidate the molecular pathways, including fractalkine/CX3CR1 and p38 MAPK, involved in DNFB-induced pruritus.
Main Methods:
- A mouse model of chronic pruritus was established using repeated 2,4-dinitrofluorobenzene (DNFB) application.
- Microglial activity, p38 MAPK signaling, and fractalkine/CX3CR1 pathways were assessed in response to DNFB treatment.
- Pharmacological inhibitors and antiserum were used to block specific pathways and observe effects on scratching behavior.
Main Results:
- DNFB treatment induced prolonged scratching behavior and spinal microglia activation.
- Inhibition of microglial activity and p38 MAPK signaling significantly reduced scratching.
- Blocking fractalkine/CX3CR1 signaling also inhibited p38 activity and decreased scratching.
Conclusions:
- Spinal microglia play a critical role in the development of DNFB-induced chronic pruritus.
- The fractalkine/CX3CR1/p38 MAPK pathway is implicated in mediating chronic itch, similar to its role in neuropathic pain.
