The role of brain-derived neurotrophic factor in experimental inflammation of mouse gut.
Previous studies suggested that brain-derived neurotrophic factor (BDNF) might act as an important modulator in chronic pain states. However, no systematic study has used knock-out mice to clarify its effect on visceral sensitivity. In the present study, 2,4,6-trinitrobenzene sulfonic acid (TNBS) was administered to heterozygous (BDNF(+/-)) knock-out and wild-type (BDNF(+/+)) mice to induce colitis. Visceral response to colorectal distension (CRD) and bladder reactivity were recorded. Results demonstrated that in normal state, BDNF(+/-) and BDNF(+/+) mice did not differ in the visceral response to CRD at <60 mm Hg pressure and the bladder reactivity; however, with 60 mm Hg pressure, BDNF(+/-) mice showed a weaker visceral response to CRD. In inflammatory state of colitis, TNBS induced upregulation of BDNF in dorsal root ganglia of both genotypes while BDNF(+/-) mice showing significantly lower sensitivity in the colon at 30 mm Hg and lower sensitivity in bladder than BDNF(+/+) mice. The two genotypes showed no significant difference in inflammatory severity. Thus, BDNF deficiency results in developmental changes in colonic nociception in both control and inflammatory states, which are more significant in inflammatory state. For bladder reactivity, BDNF deficiency leads to lower sensitization in inflammatory state but has no effect in control state.


CONCLUSIONS
This article highlights the role of BDNF in colonic and referred bladder hyperalgesia in mice. The findings might help in determining novel pharmaceutical interventions targeted at BDNF to relieve abdominal pain.
Yang
Jing
J
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Yu
Yanbo
Y
Yu
Hui
H
Zuo
Xiuli
X
Liu
Chunxi
C
Gao
Lijun
L
Chen
Zhe-Yu
ZY
Li
Yanqing
Y
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010812:Physical Stimulation; D011897:Random Allocation; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D014302:Trinitrobenzenesulfonic Acid