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Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats.

Cho SY, Ki HG, Kim JM, Oh JM, Yang JH, Kim WM, Lee HG, Yoon MH, Choi JI - Korean J Anesthesiol (2015)

Bottom Line: In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined.The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured.The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea.

ABSTRACT

Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported.

Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured.

Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats.

Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

No MeSH data available.


Related in: MedlinePlus

Representative p-ERK (phospho-extracellular signal-regulated kinase) blots along with t-ERK (total-extracellular signal-regulated kinase) and β-actin loading controls are illustrated. Intraplantar carrageenan induces a significant increase in p-ERK in dorsal spinal cord. Level of p-ERK increases at 30 min and returns to the level of naïve at 60 min after carrageenan injections in control rat. In 5,7-DHT (5,7-dihydroxytryptamine) treated rat, however, increased p-ERK expression is observed at both 30 and 60 min. Densities of t-ERK over β-actin are not different among groups (data not shown). Con and DHT on abscissa respectively represents the control and 5,7-DHT treated animals, and 30 and 60 min indicates the time following carrageenan injection. *P< 0.05, †P < 0.01, significantly different from Naive. N = 7 rats/group.
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Figure 2: Representative p-ERK (phospho-extracellular signal-regulated kinase) blots along with t-ERK (total-extracellular signal-regulated kinase) and β-actin loading controls are illustrated. Intraplantar carrageenan induces a significant increase in p-ERK in dorsal spinal cord. Level of p-ERK increases at 30 min and returns to the level of naïve at 60 min after carrageenan injections in control rat. In 5,7-DHT (5,7-dihydroxytryptamine) treated rat, however, increased p-ERK expression is observed at both 30 and 60 min. Densities of t-ERK over β-actin are not different among groups (data not shown). Con and DHT on abscissa respectively represents the control and 5,7-DHT treated animals, and 30 and 60 min indicates the time following carrageenan injection. *P< 0.05, †P < 0.01, significantly different from Naive. N = 7 rats/group.

Mentions: Intraplantar injection of the carrageenan into the hind paws of the animals elicited a clear threefold increase in the p-ERK at 30 min, compared to naive rat levels. However, it returned to the level of the naive rat at 60 min. In contrast, the animals treated with 5,7-DHT showed a significant increase in the p-ERK at 30 min, and it remained elevated at 60 min. The total-ERK expression over β-actin was not different among the naive and vehicle or 5,7-DHT-injected rats (Fig. 2).


Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats.

Cho SY, Ki HG, Kim JM, Oh JM, Yang JH, Kim WM, Lee HG, Yoon MH, Choi JI - Korean J Anesthesiol (2015)

Representative p-ERK (phospho-extracellular signal-regulated kinase) blots along with t-ERK (total-extracellular signal-regulated kinase) and β-actin loading controls are illustrated. Intraplantar carrageenan induces a significant increase in p-ERK in dorsal spinal cord. Level of p-ERK increases at 30 min and returns to the level of naïve at 60 min after carrageenan injections in control rat. In 5,7-DHT (5,7-dihydroxytryptamine) treated rat, however, increased p-ERK expression is observed at both 30 and 60 min. Densities of t-ERK over β-actin are not different among groups (data not shown). Con and DHT on abscissa respectively represents the control and 5,7-DHT treated animals, and 30 and 60 min indicates the time following carrageenan injection. *P< 0.05, †P < 0.01, significantly different from Naive. N = 7 rats/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384405&req=5

Figure 2: Representative p-ERK (phospho-extracellular signal-regulated kinase) blots along with t-ERK (total-extracellular signal-regulated kinase) and β-actin loading controls are illustrated. Intraplantar carrageenan induces a significant increase in p-ERK in dorsal spinal cord. Level of p-ERK increases at 30 min and returns to the level of naïve at 60 min after carrageenan injections in control rat. In 5,7-DHT (5,7-dihydroxytryptamine) treated rat, however, increased p-ERK expression is observed at both 30 and 60 min. Densities of t-ERK over β-actin are not different among groups (data not shown). Con and DHT on abscissa respectively represents the control and 5,7-DHT treated animals, and 30 and 60 min indicates the time following carrageenan injection. *P< 0.05, †P < 0.01, significantly different from Naive. N = 7 rats/group.
Mentions: Intraplantar injection of the carrageenan into the hind paws of the animals elicited a clear threefold increase in the p-ERK at 30 min, compared to naive rat levels. However, it returned to the level of the naive rat at 60 min. In contrast, the animals treated with 5,7-DHT showed a significant increase in the p-ERK at 30 min, and it remained elevated at 60 min. The total-ERK expression over β-actin was not different among the naive and vehicle or 5,7-DHT-injected rats (Fig. 2).

Bottom Line: In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined.The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured.The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea.

ABSTRACT

Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported.

Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured.

Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats.

Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

No MeSH data available.


Related in: MedlinePlus