Korean J Anat.  2003 Jun;36(3):237-246.

Activation of Mitogen-Activated Protein Kinases in the Rat Dorsal Root Ganglia Following Peripheral Tissue Inflammation or Nerve Injuries

• Bae JC
• Lee HL
• Lee KM
• Hwang SH
• Sohn SJ
• Kim DS
• Cho HJ

Abstract

The mitogen-activated protein kinase (MAPK) family has three members: the extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). There is substantial evidence indicating that the MAPK cascade plays a pivotal role in transducing extracellular stimuli into intracellular responses in all cells. The ERK is activated in response to growth factors, oxidative stress, increases in intracellular calcium levels, or glutamate receptor stimulation. The p38 MAPK and JNK are activated by stress signals such as inflammtory cytokines, heat shock, ultraviolet light, and ischemia. It has been shown that cytokines, growth factors, or other agents released and are retrograde-transported to the dorsal root ganglia (DRG) as a result of peripheral tissue inflammation or the degeneration of axons following peripheral nerve injuries which cause hyperalgesia. In the present study, we investigated the activation of MAPKs in rat DRG by means of immunohistochemistry following peripheral inflammation or nerve injuries. The results obtained were as follows; 1. Peripheral tissue inflammation induced significant increase in the percentage of phosphorylated (P)-ERK, P-p38 or P-JNK immunoreactive neurons in the ipsilateral L5 DRG. 2. Following axotomy, the percentage of P-ERK or P-p38 MAPK immunoreactive neurons decreased significantly and that of P-JNK showed significant increase in the ipsilateral side. 3. Chronic constriction injury of the sciatic nerve (CCI) induced similar changes with those following peripheral inflammation in the activation of MAPKs in the DRG neurons. 4. The activation of ERK, p38 MAPK and JNK following inflammation and CCI was observed primarily in small neurons, while that of JNK following axotomy was found in neurons of all sizes. These results suggest that cytokines or growth factors released as a result of peripheral inflammation or CCI of the sciatic nerve may modulate expression of P-ERK, P-p38 MAPK and P-JNK in the DRG and that MAPKs may play an important roles in pain hypersensitivity.

Keyword

Peripheral tissue inflammation; Peripheral nerve injury; Dorsal root ganglion; MAPK; Imm unohistochemistry

MeSH Terms

Animals
Axons
Axotomy
Calcium
Constriction
Cytokines
Diagnosis-Related Groups
Ganglia, Spinal*
Hot Temperature
Humans
Hyperalgesia
Hypersensitivity
Immunohistochemistry
Inflammation*
Intercellular Signaling Peptides and Proteins
Ischemia
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases*
Neurons
Oxidative Stress
p38 Mitogen-Activated Protein Kinases
Peripheral Nerve Injuries
Phosphotransferases
Protein Kinases
Rats*
Receptors, Glutamate
Sciatic Nerve
Shock
Spinal Nerve Roots*
Ultraviolet Rays
Calcium
Cytokines
Intercellular Signaling Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Phosphotransferases
Protein Kinases
Receptors, Glutamate
p38 Mitogen-Activated Protein Kinases