Abstract
Previously, we reported that nicotine withdrawal (NT) significantly increased pain sensitivity in rats. Recent reports suggest that fractalkine is involved in the spinal cord neuron-to-microglia activation via CX3CR1 signaling. However, its contribution to NT-induced hyperalgesia and the underlying mechanisms have yet to be elucidated. In the present study, a rat model of NT was used to test the changes in CX3CR1 expression in the spinal cord. We also evaluated the effect of the CX3CR1 neutralizing antibody on spinal microglial activity, the expression of phosphorylated p38-mitogen-activated protein kinase (p-p38-MAPK) and heat-induced pain responses. We established a NT model via subcutaneous injection of pure nicotine (3mg/kg), three times daily for 7days. The expression of CX3CR1 was studied by Western blot and immunofluorescence staining. Following NT, the rats received daily intrathecal injections of CX3CR1 neutralizing antibody for 3days. The change in paw withdrawal latency (PWL) was observed. The activation of microglia and the expression of p-p38-MAPK were investigated by Western blot and immunofluorescence staining. The expression of CX3CR1 was significantly increased after NT and co-localized with IBA-1. NT rats treated with CX3CR1 neutralizing antibody showed significantly increased PWL on day 4 after NT. Furthermore, the activation of microglia and the expression of p-p38-MAPK in the spinal cord were suppressed. These results indicate that microglial CX3CR1/p38MAPK pathway is critical for the development of pain hypersensitivity after NT.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
