Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body.
Inflammation of the primary afferent proximal to the dorsal root ganglion (DRG) and the DRG itself is known to produce radicular pain. Here, we examined pain-related behaviors and the activation of extracellular signal-regulated protein kinase (ERK) in the DRG after inflammation near the DRG somata. Inflammation of the L4/5 nerve roots and DRG induced by complete Freund's adjuvant (CFA) produced mechanical allodynia on the ipsilateral hindpaw and induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase (trk) A-expressing small- and medium-size neurons. This CFA-induced increase in ERK phosphorylation was mediated through trk receptors, because intrathecal treatment with the tyrosine kinase inhibitor, K252a, reduced the activation of ERK. On the other hand, an increase in brain-derived neurotrophic factor (BDNF) mRNA/protein in the DRG concomitant with the ERK activation was also observed. Furthermore, we found that nerve growth factor (NGF) injection directly into the L4/5 nerve roots and DRG produced mechanical allodynia, and an increase in the phosphorylation of ERK and BDNF expression in the DRG, but the mitogen-activated protein kinase (MAPK) kinase1/2 inhibitor, U0126, inhibited the effects induced by NGF. Therefore, we suggest that after inflammation near the cell body, NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK-MAPK. The activation of MAPK in the primary afferents may be involved in the pathophysiological mechanisms of inflammation-induced radiculopathy and MAPK pathways in the primary afferents may be potential targets for pharmacological intervention for neuropathic pain produced by inflammation near the DRG somata.
Obata
K
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Yamanaka
H
H
Dai
Y
Y
Mizushima
T
T
Fukuoka
T
T
Tokunaga
A
A
Noguchi
K
K
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005620:Freund's Adjuvant; D007839:Functional Laterality / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D026121:Indole Alkaloids; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects; D011843:Radiculopathy / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009570:Nitriles; C113580:U 0126; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020928:Mitogen-Activated Protein Kinases