Short-term anesthesia inhibits formalin-induced extracellular signal-regulated kinase (ERK) activation in the rostral anterior cingulate cortex but not in the spinal cord.
BACKGROUND
The rostral anterior cingulate cortex (rACC) has been implicated in the negative affective response to injury, and importantly, it has been shown that activation of extracellular signal-regulated kinase (ERK) signaling in the rACC contributes to the full expression of the affective component of pain in rodents. In this study, we investigated whether administration of anesthesia at the time of injury could reduce phosphorylated-ERK (PERK) expression in the rACC, which might eliminate the negative affective component of noxious stimulation. Intraplantar hindpaw formalin stimulation, an aversive event in the awake animal, was given with or without general isoflurane anesthesia, and PERK expression was subsequently quantified in the rACC using immunohistochemistry. Furthermore, as numerous studies have demonstrated the importance of spinal ERK signaling in the regulation of nociceptive behaviour, we also examined PERK in the superficial dorsal horn of the spinal cord.


RESULTS
Formalin injection with and without short-term (<10 min) general isoflurane anesthesia induced the same level of PERK expression in spinal cord laminae I-II. However, PERK expression was significantly inhibited across all laminae of the rACC in animals anesthetized during formalin injection. The effect of anesthesia was such that levels of PERK were the same in formalin and sham treated anesthesized animals.


CONCLUSIONS
This study is the first to demonstrate that isoflurane anesthesia can inhibit formalin-induced PERK in the rACC and therefore might eliminate the unpleasantness of restraint associated with awake hindpaw injection.
Department of Cell and Developmental Biology, University College London, London, UK. k.tochiki@ucl.ac.uk.
Keri K
KK
Tochiki
Department of Cell and Developmental Biology, University College London, London, UK. m.maiaru@ucl.ac.uk.
Maria
M
Maiarù
Department of Cell and Developmental Biology, University College London, London, UK. j.miller@prion.ucl.ac.uk.
James R C
JR
Miller
Department of Cell and Developmental Biology, University College London, London, UK. hunt@ucl.ac.uk.
Stephen P
SP
Hunt
Department of Cell and Developmental Biology, University College London, London, UK. ucgasmg@ucl.ac.uk.
Sandrine M
SM
Géranton
D000758:Anesthesia; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors
D005557:Formaldehyde; D048049:Extracellular Signal-Regulated MAP Kinases