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Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats.

Kwon SY, Yeom JH, Joo JD - Korean J Anesthesiol (2014)

Bottom Line: After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines.Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.

ABSTRACT

Background: Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain.

Methods: The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.

Results: In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNFα and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group.

Conclusions: In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

No MeSH data available.


Related in: MedlinePlus

Time course of the paw withdrawal threshold to mechanical stimuli applied to the plantar surface of the affected left paw with von Frey filaments in a rat model of neuropathic pain. The withdrawal threshold was measured under continuous infusion of saline or ketamine through an implanted mini-osmotic pump. Values are mean ± SEM (SEM = 0 in 1 day to 3 day, n = 8 in each group). *P < 0.05 compared to NP + NS group by analysis of variance (ANOVA).
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Figure 1: Time course of the paw withdrawal threshold to mechanical stimuli applied to the plantar surface of the affected left paw with von Frey filaments in a rat model of neuropathic pain. The withdrawal threshold was measured under continuous infusion of saline or ketamine through an implanted mini-osmotic pump. Values are mean ± SEM (SEM = 0 in 1 day to 3 day, n = 8 in each group). *P < 0.05 compared to NP + NS group by analysis of variance (ANOVA).

Mentions: Among neuropathic rats confirmed through behavioral testing that received implanted mini-osmotic pumps and were observed for one week with a paw withdrawal threshold test, the NP + Keta group showed notable recovery of withdrawal threshold after the 4th day of testing. However, the NP + NS group maintained its threshold without a significant difference (Fig. 1). The western blot analysis using brain tissues and the mRNA expression comparison after RT-PCR of TNFα and ICAM1 showed no significant differences among the control group, the NP + NS group, and the NP + Keta group. However, the quantitative changes of phospho-p38 MAPK and total p38 MAPK observed in the spinal cord tissues were seen to be 178.4 ± 17.9 and 238.4 ± 26.8 respectively, in the NP + NS group. These values represented increases of 76 and 127% (P = 0.003, 0.001, respectively) from the control group values of 101.4 ± 10.4 and 104.9 ± 16.4. In contrast, the NP + Keta group showed significant decreases (P = 0.004, 0.005, respectively) of 75 and 93% from the values of the NP + NS group, to 102.1 ± 12.3 and 123.7 ± 14.8 (Fig. 2). There were no significant differences in signaling protein changes between the NP + Keta group and the control group (Fig. 2). The RT-PCR analysis on TNFα and ICAM1 in the spinal nerves showed a noticeable increase in the mRNA expression of TNFα and ICAM1 in the NP + NS group compared to the control group (P = 0.008, 0.006, respectively). On the other hand, the NP + Keta group had its mRNA expression of TNFα and, ICAM1 significantly decreased in comparison to the NP + NS group (P = 0.02, 0.002, respectively), but showed no significant changes in comparison to the control group (Fig. 3).


Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats.

Kwon SY, Yeom JH, Joo JD - Korean J Anesthesiol (2014)

Time course of the paw withdrawal threshold to mechanical stimuli applied to the plantar surface of the affected left paw with von Frey filaments in a rat model of neuropathic pain. The withdrawal threshold was measured under continuous infusion of saline or ketamine through an implanted mini-osmotic pump. Values are mean ± SEM (SEM = 0 in 1 day to 3 day, n = 8 in each group). *P < 0.05 compared to NP + NS group by analysis of variance (ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927002&req=5

Figure 1: Time course of the paw withdrawal threshold to mechanical stimuli applied to the plantar surface of the affected left paw with von Frey filaments in a rat model of neuropathic pain. The withdrawal threshold was measured under continuous infusion of saline or ketamine through an implanted mini-osmotic pump. Values are mean ± SEM (SEM = 0 in 1 day to 3 day, n = 8 in each group). *P < 0.05 compared to NP + NS group by analysis of variance (ANOVA).
Mentions: Among neuropathic rats confirmed through behavioral testing that received implanted mini-osmotic pumps and were observed for one week with a paw withdrawal threshold test, the NP + Keta group showed notable recovery of withdrawal threshold after the 4th day of testing. However, the NP + NS group maintained its threshold without a significant difference (Fig. 1). The western blot analysis using brain tissues and the mRNA expression comparison after RT-PCR of TNFα and ICAM1 showed no significant differences among the control group, the NP + NS group, and the NP + Keta group. However, the quantitative changes of phospho-p38 MAPK and total p38 MAPK observed in the spinal cord tissues were seen to be 178.4 ± 17.9 and 238.4 ± 26.8 respectively, in the NP + NS group. These values represented increases of 76 and 127% (P = 0.003, 0.001, respectively) from the control group values of 101.4 ± 10.4 and 104.9 ± 16.4. In contrast, the NP + Keta group showed significant decreases (P = 0.004, 0.005, respectively) of 75 and 93% from the values of the NP + NS group, to 102.1 ± 12.3 and 123.7 ± 14.8 (Fig. 2). There were no significant differences in signaling protein changes between the NP + Keta group and the control group (Fig. 2). The RT-PCR analysis on TNFα and ICAM1 in the spinal nerves showed a noticeable increase in the mRNA expression of TNFα and ICAM1 in the NP + NS group compared to the control group (P = 0.008, 0.006, respectively). On the other hand, the NP + Keta group had its mRNA expression of TNFα and, ICAM1 significantly decreased in comparison to the NP + NS group (P = 0.02, 0.002, respectively), but showed no significant changes in comparison to the control group (Fig. 3).

Bottom Line: After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines.Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.

ABSTRACT

Background: Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain.

Methods: The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.

Results: In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNFα and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group.

Conclusions: In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

No MeSH data available.


Related in: MedlinePlus