Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice

Authors
R Randhi, M Damon, KJ Dixon

Lab
Virginia Commonwealth University, Richmond, VA, USA

Journal
BMC Gastroenterology

Abstract
BackgroundMethods Acute pancreatitis was induced in adult male C57Bl/6J mice by administering cerulein (8 injections of 50 microg/kg I.P., spaced an hour apart), with XPro1595 (10 mg/kg, S.C.) or vehicle being administered approximately 18 h after the last injection. Serum was collected 6 or 18 h after the last cerulein injection, pancreatic tissue was collected 2 and 7 days post-induction, and brain hippocampal tissue was collected at 7 days post-induction. The animal’s pain level was assessed 3, 5 and 7 days post-induction.
Results The induction of acute pancreatitis promoted a strong increase in serum amylase levels, which had receded back to baseline levels by the next morning. XPro1595 treatment began after amylase levels had subsided at 18 h, and prevented pancreatic immune cell infiltration, that subsequently prevented tissue disruption and acinar cell death. These improvements in pathology were associated with a significant reduction in mechanical hypersensitivity (neuropathic pain). XPro1595 treatment also prevented an increase in hippocampal astrocyte reactivity, that may be associated with the prevention of neuropathic pain in this mouse model.
Conclusion Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of cerulein-induced pancreatitis in mice, which provides support of its use in patients with pancreatitis.

BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)