Spinal microglia and neuropathic pain in young rats.
Neuropathic pain behaviour is not observed in neonatal rats and tactile allodynia does not develop in the spared nerve injury (SNI) model until rats are 4 weeks of age at the time of surgery. Since activated spinal microglia are known to play a key role in neuropathic pain, we have investigated whether the microglial response to nerve injury in young rats differs from that in adults. Here we show that dorsal horn microglial activation, visualised with IBA-1 immunostaining, is significantly less in postnatal day (P) 10 rat pups than in adults, 7 days after SNI. This was confirmed by qPCR analysis of IBA-1 mRNA and mRNA of other microglial markers, integrin-alpha M, MHC-II DMalpha and MHC-II DMbeta. Dorsal horn IBA-1+ve microglia could be activated, however, by intraspinal injections of lipopolysaccharide (LPS) or N-methyl-d-aspartate (NMDA) at P10, although the increase in the levels of mRNA for all microglial markers was less than in the adult rat. In addition, P10 rats developed a small but significant mechanical allodynia in response to intrathecal LPS. Intrathecal injection of cultured ATP-activated microglia, known to cause mechanical allodynia in adult rats, had no behavioural effect at P10 and only began to cause allodynia if injections were performed at P16. The results clearly demonstrate immaturity of the microglial response triggered by nerve injury in the first postnatal weeks which may explain the absence of tactile allodynia following peripheral nerve injury in young rats.
Moss
Andrew
A
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK The University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Beggs
Simon
S
Vega-Avelaira
David
D
Costigan
Michael
M
Hathway
Gareth J
GJ
Salter
Michael W
MW
Fitzgerald
Maria
M
D000375:Aging / Q000276:immunology*; D000818:Animals; D006930:Hyperalgesia / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology*; D010523:Peripheral Nervous System Diseases / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology*