Altered response to formalin by L5 spinal nerve ligation in rats: a behavioral and molecular study.
BACKGROUND
The status of neuropathic pain alters the responsiveness to formalin injection in rats. However, the mechanism by which this alteration occurs is unknown.


METHODS
We used immunocytochemistry to examine the expression of brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the spinal cord of rats with L5 spinal nerve ligation (SNL)-induced neuropathy, and investigated the expression of c-Fos in the spinal cord after injection of formalin in the hindpaw of rats with SNL.


RESULTS
Four weeks after SNL, the withdrawal threshold was significantly lower in the SNL group than in the sham-operated (sham) group (n = 12 per group, P < 0.05). In the SNL group, expression of BDNF in the L4 (P < 0.05) and L5 (P < 0.01) superficial dorsal horn was significantly decreased compared to that in the sham group. CGRP protein in the L5 but not in the L4, dorsal horn was significantly decreased compared to that in the sham group (P < 0.01). After formalin injection, spontaneous pain responses in the SNL group were significantly decreased compared to those in the sham group (P < 0.05). Immunolabeling for c-Fos was significantly decreased in the L4 and L5 dorsal horn in the SNL group (P < 0.01).


CONCLUSIONS
Our examination of c-Fos distribution indicates that decreased neuronal activity in the spinal cord in response to inflammatory pain may be important for altering the perception of acute pain. Decreased BDNF expression in response to SNL-induced neuropathy may be involved in this alteration.
Kaku
Ryuji
R
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City 700-8558, Japan.
Yokoyama
Masataka
M
Kobayashi
Hiroyuki
H
Matsuoka
Yoshikazu
Y
Sato
Tetsufumi
T
Mizobuchi
Satoshi
S
Itano
Yoshitaro
Y
Morita
Kiyoshi
K
D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005557:Formaldehyde; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000523:psychology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology; D010147:Pain Measurement; D017288:Pain Threshold; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013127:Spinal Nerves / Q000601:surgery*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; D015740:Calcitonin Gene-Related Peptide