Premium
Intra‐neural administration of fractalkine attenuates neuropathic pain‐related behaviour
Author(s) -
Holmes Fiona E.,
Arnott Nighat,
Vanderplank Penny,
Kerr Niall C. H.,
Longbrake Erin E.,
Popovich Philip G.,
Imai Toshio,
Combadière Christophe,
Murphy Philip M.,
Wynick David
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05419.x
Subject(s) - sni , nerve injury , neuropathic pain , sciatic nerve , axotomy , cx3cr1 , medicine , allodynia , sciatic nerve injury , knockout mouse , anesthesia , endocrinology , receptor , chemokine , chemokine receptor , hyperalgesia , pharmacology , central nervous system , nociception , chemistry , biochemistry , hydrolysis , acid hydrolysis
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.