Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization.
BACKGROUND
In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal.


RESULTS
In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail.


CONCLUSIONS
These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP.
Mika
M
Ohmichi
Yusuke
Y
Ohmichi
Hitoshi
H
Ohishi
Takahiko
T
Yoshimoto
Atsuko
A
Morimoto
Yuqiang
Y
Li
Hiroki
H
Sakurai
Takashi
T
Nakano
Research Institute of Environmental Medicine, Nagoya University, Aichi 464-8601, Japan. jsato@nagoya-u.jp.
Jun
J
Sato
D015074:2-Aminoadipic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D002370:Casts, Surgical; D059350:Chronic Pain / Q000378:metabolism / Q000473:pathology*; D003050:Coccyx / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006614:Hindlimb / Q000473:pathology; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology*; D007103:Immobilization; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D039481:CD11b Antigen; D015074:2-Aminoadipic Acid; D048049:Extracellular Signal-Regulated MAP Kinases