1. Chemokine contribution to neuropathic pain: Respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons 吕晓鹏 PAIN 2014.8.5

2. Introduction 神经病理性疼痛（ neuropathic pain ）是指由于中 枢神经系统和周围神经系统的躯体感觉传递紊乱 而导致的一组疼痛综合征，其产生的原因包括： 神经压迫、神经切断、中风、脊髓外伤、糖尿病、 病毒感染后的神经病变等。

3. Introduction Neuroinflammation has been recently recognized for its pivotal role in the pathogenesis of neuropathic pain as well as in inflammatory pain.

4. Introduction 趋化因子也称化学趋化性细胞因子 （ chemoattractant cytokines ），属于细胞因子中的 一个超家族，是一组功能相似、由组织细胞和免 疫活性细胞产生、具有多种生物学功能的分泌性 小分子。

5. Introduction Chemokines have been demonstrated to regulate neuroinflammation at different anatomical locations, including nerve, dorsal root ganglion (DRG), spinal cord, and brain.

6. Introduction Recent studies have shown that spinal nerve ligation and localized inflammation of DRG induced rapid upregulation of CXCL1 in the DRG. Intraplantar or intraarticular injection of CXCL1 produced mechanical hyperalgesia in rodents.

7. Introduction These studies suggest a pronociceptive role for CXCL1 in the peripheral nervous system. But it is virtually unknown whether and how central (spinal) CXCL1 would play a role in the genesis of neuropathic pain.

8. Materials Mice: spinal nerve ligation (SNL) neuropathic pain model Cell: Astrocytes

9. Results Fig 1. CXCL1 is upregulated in spinal cord astrocytes after nerve injury

10. Fig 2. TNFa drives spinal CXCL1 expression after nerve injury

11. Fig 3. JNK pathway is required for CXCL1 upregulation in cultured astrocytes and spinal cord

12. Fig 4. Intrathecal injection of CXCL1 neutralizing antibody transiently attenuates SNL-induced neuropathic pain.

13. Fig 5. Intraspinal injection of recombinant lentivirus-CXCL1 shRNA persistently suppresses SNL-induced neuropathic pain

14. Fig 6. Spinal injection of CXCL1 induces heat hyperalgesia via CXCR2

15. Fig 7. CXCL1 increases the expression of pERK, pCREB, and c-Fos in spinal cord neurons

16. Fig 8. Spinal nerve ligation (SNL) induces CXCR2 upregulation in spinal cord neurons

17. Conclusion Inhibition of the CXCL1-CXCR2 signaling may offer a new therapy for neuropathic pain management.

18. Thank you!