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: L Pei, J Zhang, F Zhao, T Su, H Wei, J Tian, M Li, J Shi
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 107 Issue 6 Pg. 948-58 (Dec 2011) ISSN: 1471-6771 [Electronic] England
• PMID: 21990306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A1
• FPR2 protein, human
• Receptors, Formyl Peptide
• Receptors, Lipoxin
• Freund's Adjuvant

Topics

• Amino Acid Sequence
• Animals
• Annexin A1 (analysis, physiology)
• Freund's Adjuvant (pharmacology)
• Ganglia, Spinal (physiology)
• Inflammation (physiopathology)
• Male
• Molecular Sequence Data
• Nociception
• Pain (physiopathology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Formyl Peptide (analysis, physiology)
• Receptors, Lipoxin (analysis, physiology)