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Short-term anesthesia inhibits formalin-induced extracellular signal-regulated kinase (ERK) activation in the rostral anterior cingulate cortex but not in the spinal cord.

Tochiki KK, Maiarù M, Miller JR, Hunt SP, Géranton SM - Mol Pain (2015)

Bottom Line: 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.However, PERK expression was significantly inhibited across all laminae of the rACC in animals anesthetized during formalin injection.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London, UK. k.tochiki@ucl.ac.uk.

ABSTRACT

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.

Findings: 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.

No MeSH data available.


Related in: MedlinePlus

Short general anesthesia modulates formalin induced PERK expression in the rACC. a Typical PERK expression in area Cg1 of the rACC at Bregma 2.7 mm for each treatment group. Scale bar 50 µm. b Quantification of PERK expression across rACC Bregma points using bins. *P < 0.05, **P < 0.01, data presented as mean ± SEM (n = 3 each group).
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Fig2: Short general anesthesia modulates formalin induced PERK expression in the rACC. a Typical PERK expression in area Cg1 of the rACC at Bregma 2.7 mm for each treatment group. Scale bar 50 µm. b Quantification of PERK expression across rACC Bregma points using bins. *P < 0.05, **P < 0.01, data presented as mean ± SEM (n = 3 each group).

Mentions: We found a bilateral up-regulation of PERK across all laminae of the rACC 30 min post-formalin stimulation of the hindpaw, as reported by others [5, 6], and therefore combined the counts from the ipsilateral and contralateral side for further analysis. Strikingly, although anesthesia did not lead to differences in spinal cord PERK activation, it had a significant effect on PERK expression in the rACC (effect of anesthesia ANOVA F(1,24) = 9.75, P < 0.01) (Fig. 2). LSD post hoc analysis revealed that PERK expression in the Form (+) and A (−) group was greater than in the Form (−) and A (−) group (P < 0.05), Form (−) and A (+) group (P < 0.01) and the Form (+) and A (+) group (P < 0.01). Interestingly, there was no difference between the Form (+) and A (+) group and the Form (−) and A (+) group suggesting that increased PERK expression in the rACC could only be seen with the combined condition of handling/restraint and formalin injection.Fig. 2


Short-term anesthesia inhibits formalin-induced extracellular signal-regulated kinase (ERK) activation in the rostral anterior cingulate cortex but not in the spinal cord.

Tochiki KK, Maiarù M, Miller JR, Hunt SP, Géranton SM - Mol Pain (2015)

Short general anesthesia modulates formalin induced PERK expression in the rACC. a Typical PERK expression in area Cg1 of the rACC at Bregma 2.7 mm for each treatment group. Scale bar 50 µm. b Quantification of PERK expression across rACC Bregma points using bins. *P < 0.05, **P < 0.01, data presented as mean ± SEM (n = 3 each group).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536792&req=5

Fig2: Short general anesthesia modulates formalin induced PERK expression in the rACC. a Typical PERK expression in area Cg1 of the rACC at Bregma 2.7 mm for each treatment group. Scale bar 50 µm. b Quantification of PERK expression across rACC Bregma points using bins. *P < 0.05, **P < 0.01, data presented as mean ± SEM (n = 3 each group).
Mentions: We found a bilateral up-regulation of PERK across all laminae of the rACC 30 min post-formalin stimulation of the hindpaw, as reported by others [5, 6], and therefore combined the counts from the ipsilateral and contralateral side for further analysis. Strikingly, although anesthesia did not lead to differences in spinal cord PERK activation, it had a significant effect on PERK expression in the rACC (effect of anesthesia ANOVA F(1,24) = 9.75, P < 0.01) (Fig. 2). LSD post hoc analysis revealed that PERK expression in the Form (+) and A (−) group was greater than in the Form (−) and A (−) group (P < 0.05), Form (−) and A (+) group (P < 0.01) and the Form (+) and A (+) group (P < 0.01). Interestingly, there was no difference between the Form (+) and A (+) group and the Form (−) and A (+) group suggesting that increased PERK expression in the rACC could only be seen with the combined condition of handling/restraint and formalin injection.Fig. 2

Bottom Line: 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.However, PERK expression was significantly inhibited across all laminae of the rACC in animals anesthetized during formalin injection.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London, UK. k.tochiki@ucl.ac.uk.

ABSTRACT

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.

Findings: 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.

No MeSH data available.


Related in: MedlinePlus