Astrocytic activation in thoracic spinal cord contributes to persistent pain in rat model of chronic pancreatitis.
One of the most important symptoms in chronic pancreatitis (CP) is constant and recurrent abdominal pain. However, there is still no ideal explanation and treatment on it. Previous studies indicated that pain in CP shared many characteristics of neuropathic pain. As an important mechanism underlying neuropathic pain, astrocytic activation is probably involved in pain of CP. Based on the trinitrobenzene sulfonic acid (TNBS)-induce rat CP model, we performed pancreatic histology to assess the severity of CP with semiquantitative scores and tested the nociceptive behaviors following induction of CP. Glial fibrillary acidic protein (GFAP) expressions in the thoracic spinal cord were observed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, we injected intrathecally astrocytic specific inhibitor l-alpha-aminoadipate (LAA) and observed its effect on nociception induced by CP. Compared to the naive and sham group, TNBS produced long lasting pancreatitis, and persistent mechanical hypersensitivity in the abdomen that was evident 1 week after TNBS infusion and persisted up to 5 weeks. Compared with naive or sham operated rats, GFAP staining was significantly increased 5 weeks after CP induction. Real-time RT-PCR indicated that GFAP expression was significantly increased in TNBS treated rats compared to the sham group. TNBS-induced astrocytic activation was significantly attenuated by LAA, compared with the saline control. Treatment with LAA significantly, even though not completely, attenuated the allodynia. Our results provide for the first time that astrocytes may play a critical role in pain of CP. Some actions could be taken to prevent astrocytic activation to treat pain in CP patients.
Feng
Q X
QX
Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, PR China.
Wang
W
W
Feng
X Y
XY
Mei
X P
XP
Zhu
C
C
Liu
Z C
ZC
Li
Y Q
YQ
Dou
K F
KF
Zhao
Q C
QC
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013909:Thorax; D014110:Touch; D014302:Trinitrobenzenesulfonic Acid
D015074:2-Aminoadipic Acid; D014302:Trinitrobenzenesulfonic Acid