title: Annexin 1 exerts anti-nociceptive effects after peripheral inflammatory pain through formyl-peptide-receptor-like 1 in rat dorsal root ganglion.
abstract: BACKGROUND
  Annexin 1 (ANXA1) has analgesic effects in inflammatory pain. We aimed to investigate the anti-nociceptive role of ANXA1, at the dorsal root ganglion (DRG) level, through an interaction with formyl-peptide-receptor-like 1 (FPR2/ALX).
  
  
  METHODS
  Inflammatory pain was evoked by injecting complete Freund's adjuvant (CFA, 50 μl) into the hindpaw of male Sprague-Dawley rats. The distribution of ANXA1 and FPR2/ALX in L4/5 DRGs was evaluated by immunofluorescence. The expression of ANXA1 was measured by western blot. The involvement of FPR2/ALX in the anti-nociception of ANXA1 was investigated by thermal (irradiant heat) and mechanical (von Frey filament) pain tests with intrathecal (i.t.) ANXA1-derived peptide (Anxa1(2-26)), FPR2/ALX agonist 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), and antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe (Boc1).
  
  
  RESULTS
  ANXA1 and FPR2/ALX localized in the satellite glial cells and neurones in L4/5 DRGs. CFA treatment (n=20) increased ANXA1 expression in L4/5 DRGs within 7 days (P<0.01). I.T. Anxa1(2-26) (20 and 100 µg µl(-1)) and BML-111 (10 and 100 nmol) reduced CFA-induced thermal and mechanical nociception within 48 h (n=40) (P<0.05). However, i.t. Boc1 10 µg intensified inflammatory pain (P<0.05) and reversed the anti-nociceptive effect of Anxa1(2-26) (n=25) (P<0.05). Moreover, ANXA1 expression increased in L4/5 DRGs after i.t. Anxa1(2-26) (20 µg µl(-1)) (P<0.05) and BML-111 (10 nmol) (P<0.01) but decreased after i.t. Boc1 (10 and 100 µg) alone (P<0.01) or Boc1 (10 µg) co-injection with Anxa1(2-26) (20 µg µl(-1)) (P<0.05).
  
  
  CONCLUSIONS
  Endogenous ANXA1 expression at the DRG level is involved in CFA-induced inflammatory pain, and i.t. ANXA1 20 µg µl(-1) produces its anti-nociceptive effect through FPR2/ALX.
authors: Department of Neurobiology and Key Laboratory of Neurological Diseases of Hubei Province,  Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030,  PR China.
authors: L
authors: L
authors: Pei
authors: J
authors: J
authors: Zhang
authors: F
authors: F
authors: Zhao
authors: T
authors: T
authors: Su
authors: H
authors: H
authors: Wei
authors: J
authors: J
authors: Tian
authors: M
authors: M
authors: Li
authors: J
authors: J
authors: Shi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017305:Annexin A1 / Q000032:analysis / Q000502:physiology*; D005620:Freund's Adjuvant / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D059225:Nociception; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide / Q000032:analysis / Q000502:physiology*; D044067:Receptors, Lipoxin / Q000032:analysis / Q000502:physiology*
chemical_list: D017305:Annexin A1; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D005620:Freund's Adjuvant