Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat.
Peripheral nerve injury commonly leads to neuropathic pain states fostered, in part, by neuroimmunologic events. We used two models of neuropathic pain (L5 spinal nerve cryoneurolysis (SPCN) and chronic constriction injury (CCI)) to assess the role of spinal glial activation responses in producing pain behaviors. Scoring of glial responses subjectively encompassed changes in cell morphology, cell density and intensity of immunoreactivity with specific activation markers (OX-42 and anti-glial fibrillary acidic protein (GFAP) for microglia and astrocytes, respectively). Glial responses were compared with tactile sensitivity (mechanical allodynia) at 1, 3 or 10 days following SPCN and with thermal hyperalgesia at 10 days in the CCI group. Neuropathic pain behaviors preceded and did not closely correlate with microglial responses in either model. Perineural application of bupivacaine prior to SPCN prevented spinal microglial responses but not pain behaviors. Spinal astrocytic responses to SPCN were early, robust and not altered by bupivacaine. The current findings support the use of bupivacaine as a tool to suppress microglial activation and challenge the putative role of microglia in initiating or potentiating pain behaviors which result from nerve injury.
Colburn
R W
RW
Department of Pharmacology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. raymond.colburn@dartmouth.edu
DeLeo
J A
JA
Rickman
A J
AJ
Yeager
M P
MP
Kwon
P
P
Hickey
W F
WF
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002045:Bupivacaine / Q000494:pharmacology; D005615:Freezing; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000502:physiology*; D009408:Nerve Compression Syndromes / Q000503:physiopathology / Q000523:psychology; D010146:Pain / Q000523:psychology*; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013127:Spinal Nerves / Q000293:injuries; D014947:Wounds and Injuries / Q000503:physiopathology* / Q000523:psychology*
D000779:Anesthetics, Local; D002045:Bupivacaine