Microglial CX3CR1 signaling mediates stress-induced pain behavior in mice

To investigate the role of CX3CR1 in a mouse model of stress-induced pain.

Animal Model: Female and male CX3CR1-deficient (KO) and C57Bl/6J wild-type (WT) mice were exposed to chronic restraint stress (CRS) for 2 weeks.
Pain Assessment: Mechanical and cold sensitivity were assessed before and during CRS.
Microglial and Astrocyte Analysis: Microglia-IBA1 and astrocyte-GFAP activation were analyzed in stress- and pain-related brain regions.
Pharmacological Validation: Pharmacological validation was performed using the CX3CR1 antagonist, AZD8797 in WT mice.

In WT animals, CRS induced approximately 20% mechanical and 60-70% cold hyperalgesia.
Mechanical pain and cold sensitivity was significantly reduced in stressed CX3CR1 KO mice.
CRS caused microglia and astrocyte integrated density increases in WT but not CX3CR1 KO mice.
Microglia coverage of neurons was greater in the S1HL region of KO animals.
Pharmacological blockade of CX3CR1 abolished CRS-evoked mechanical but not cold hyperalgesia.

Microglial CX3CR1 signaling contributes to chronic stress-induced pain through neuroinflammatory mechanisms and central pain sensitization.

The study suggests that CX3CR1 may play a role in chronic primary pain conditions.