title: Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat.
abstract: BACKGROUND
  Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain.
  
  
  RESULTS
  To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO) dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1.
  
  
  CONCLUSIONS
  These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Nian-Song
authors.initials: NS
authors.lastname: Qian
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Liao
authors.forename: Quan-Xing
authors.initials: QX
authors.lastname: Feng
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
authors.forename: Kai-Shan
authors.initials: KS
authors.lastname: Tao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D050500:Pancreatitis, Chronic / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha