Intra-neural administration of fractalkine attenuates neuropathic pain-related behaviour.
There is increasing evidence that a number of cytokines and their receptors are involved in the processes that lead to the development and maintenance of neuropathic pain states. Here we demonstrate that levels of CX3CR1 (the receptor for the chemokine fractalkine) mRNA in lumbar dorsal root ganglia (DRG) increase 5.8-fold 7 days after sciatic nerve axotomy, and 1.7- and 2.9-fold, 3 and 7 days respectively, after the spared nerve injury (SNI) model of neuropathic pain. In contrast, no significant change in the levels of fractalkine mRNA is apparent in the DRG after axotomy or SNI. The increase in CX3CR1 mRNA is paralleled by a 3.9- and 2.1-fold increase in the number of CX3CR1-positive macrophages in the DRG 7 days after axotomy and SNI, respectively. Expression of CX3CR1 in macrophages is also markedly increased in the sciatic nerve proximal to site of injury, by 25.7-fold after axotomy and 16.2-fold after SNI, 7 days after injury. Intra-neural injection into the sciatic nerve of 400 ng or 100 ng of fractalkine in adult 129OlaHsd mice significantly delayed the development of allodynia for 3 days following SNI. Further, CX3CR1 knockout (KO) mice display an increase in allodynia for three weeks after SNI compared to strain-matched Balb/c controls. Taken together, these results suggest an anti-allodynic role for fractalkine and its receptor in the mouse.
Holmes
Fiona E
FE
Departments of Physiology and Pharmacology and Clinical Sciences South Bristol, University of Bristol, Bristol, UK. F.E.Holmes@bristol.ac.uk
Arnott
Nighat
N
Vanderplank
Penny
P
Kerr
Niall C H
NC
Longbrake
Erin E
EE
Popovich
Philip G
PG
Imai
Toshio
T
Combadière
Christophe
C
Murphy
Philip M
PM
Wynick
David
D
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics; D012585:Sciatica / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000700:Analgesics; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C471885:Cx3cr1 protein, mouse; D012333:RNA, Messenger; D019707:Receptors, Chemokine