Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior.
The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid-sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor. To evaluate the role of p11 in peripheral pain pathways, we generated a loxP-flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11 exclusively from nociceptive primary sensory neurons in mice. p11-null neurons showed deficits in the expression of Na(V)1.8, but not of annexin 2. Damage-sensing primary neurons from these animals show a reduced tetrodotoxin-resistant sodium current density, consistent with a loss of membrane-associated Na(V)1.8. Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly compromised. Acute pain behavior was attenuated in certain models, but no deficits in inflammatory pain were observed. A significant deficit in neuropathic pain behavior was also apparent in the conditional-null mice. These results confirm an important role for p11 in nociceptor function.
Foulkes
Thomas
T
Molecular Nociception Group, Department of Biology, University College London, London WC1E 6BT, United Kingdom.
Nassar
Mohammed A
MA
Lane
Tim
T
Matthews
Elizabeth A
EA
Baker
Mark D
MD
Gerke
Volker
V
Okuse
Kenji
K
Dickenson
Anthony H
AH
Wood
John N
JN
D000818:Animals; D017306:Annexin A2 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D002478:Cells, Cultured; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D009418:S100 Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human