title: Early Repeated Administration of CXCR4 Antagonist AMD3100 Dose-Dependently Improves Neuropathic Pain in Rats After L5 Spinal Nerve Ligation.
abstract: AMD3100 is a specific C-X-C chemokine receptor type 4 (CXCR4) antagonist which blocks the interaction between CXCR4 and CXCL12. Multiple lines of evidence suggest that AMD3100 has analgesic effects on many pathological pain states, including peripheral neuropathic pain. However, little is known about the underlying mechanisms. In the current study, we investigated the effect of different doses of AMD3100 on neuropathic pain in rats after L5 spinal nerve ligation. We used naloxone methiodide (NLXM) to further determine whether AMD3100-mediated analgesic effect was opioid-dependent. Behavioral study showed that early repeated administration of AMD3100 (2 and 5 mg/kg, i.p.) dose-dependently alleviates peripheral neuropathic pain. Flow cytometry, immunofluorescence and NLXM experiments showed that AMD3100 alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. Furthermore, we found that pro-inflammatory cytokines were down-regulated by AMD3100 using Enzyme-linked Immunosorbent Assay. Our data indicate that AMD3100 dose-dependently alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. This finding suggests that AMD3100 may be a viable pharmacotherapeutic strategy for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Beijing, 100020, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Beijing, 100020, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Beijing, 100020, China.
authors.forename: Xueyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, Medical Center, Tsinghua University, Beijing, 102218, China.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Chao
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Beijing, 100020, China. yueyun@hotmail.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yue
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D008026:Ligation / Q000379:methods; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000601:surgery; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries
chemical_list: D000701:Analgesics, Opioid; D001596:Benzylamines; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D009292:Narcotic Antagonists; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: AMD3100; Analgesic effect; Neuropathic pain; Opioid