1.1 “Plumbing”Problems
Traditionally，it is generally accepted that pain is generated by increased pressure in the pancreatic ductal system or in the pancreatic parenchyma due to duct obstruction，stricture and/or peripancreatic fibrosis（Lieb et al.2009；Anderson et al.2015）.Thus the“the plumbing theory”has been the theoretical background for most interventions with the common purpose to alleviate the increased pressure through different surgical and endoscopic drainage procedures（Anaparthy and Pasricha 2008）.
1.1.1 Ductal Pressure and Pain
White and co-workers described the first case report of a relationship between pancreatic duct pressure and pain in 1970（White and Bourde 1970）.Following acute necrotizing pancreatitis，a patient underwent open necrosectomy and with a drainage catheter communicating the pancreatic duct，he reproducibly reported pain with increased ductal pressure（White and Bourde 1970）.Later studies attempted to verify the consumptiocccccn while most of them were flawed by inappropriate methodology（Fasanella et al.2007）.In a study by Sato and co-workers reported that compared to patients with gastric cancer，intraoperative measured pancreatic ductal pressure significantly increased in CP patients（Sato et al.1986）.Moreover，another study reconfirmed the ductal hypertension during endoscopic management（Okazaki et al.1986）.However other studies with the same manometry reported no ductal hypertension（Laugier 1994；Rolny et al.1986；Ugljesić et al.1996；Vestergaard et al.1994），and demonstrated no difference in pressure levels referring to pain（Novis et al.1985），which was supported by another study with the finding that ductal pressure did not precisely predict the ductal decompression（Renou et al.2000）.Furthermore，the link between ductal hypertension and pain in CP remains speculative as the mechanism was unclear.
1.1.2 Parenchymal Pressure and Pain
Increased parenchymal pressure measurement of the pancreas has also been suggested as a cause of pancreatic pain.A pioneer study was done by Ebbehøj and co-workers，which depicted a novel needle probe inserted directly into the pancreatic parenchyma to measure parenchymal pressure（Ebbehøj et al.1984）.In a cohort of 39 CP patients，patients with pain resulted in higher intrapancreatic pressure and pain was relieved after surgical drainage（Ebbehøj et al.1990a）.In a 1-year study，it was reported that recurrent pain can cause rebound of increased intrapancreatic pressure（Ebbehøj et al.1990b）.However，these findings were flawed by inclusion of patients without pain and not reproduced in a more recent study using a similar technique（Manes et al.1994）.(https://www.daowen.com)
The pathophysiological link between increased intrapancreatic pressure and pain has been described as a“compartment-like syndrome”（Fasanella et al.2007）.In an animal model of CP，increased interstitial pressures，diminished blood flow and ensuing tissue acidosis were documented after stimulation with cholecystokinin and secretin（Patel et al.1995）.A human controlled experiment reported in the same paper drew a conclusion that the CP patients demonstrated significantly more acidotic tissue，which was suggested to be the result of secondary ischemia mimicking the pathophysiology underlying muscular compartment syndrome（Zhu et al.2011；Schwartz et al.2013）（described further below）.Nonetheless，it must be underlined that these findings have never been reproduced.
1.1.3 Pancreatic Morphology and Pain
As measurement of pancreatic pressure can be invasive and potentially harmful，most decisions regarding surgery or endotherapy to relieve pain in the clinic rely on morphological abnormalities of the pancreas，such as pancreatic duct stricture，obstruction or pseudocysts（Lieb et al.2009；Fasanella et al.2007；Warshaw et al.1998）.Yet the correlation between morphological changes and pain have been challenged by a number of studies demonstrating no obvious morphological difference referring to pain，and even severe pain（Bornman et al.1980；Lankisch et al.1993；Malfertheiner et al.1987；Jensen et al.1984）.The largest study examining the association between abdominal imaging features and pancreatic pain was done by Wilcox and co-workers（2015）.Of the 518 CP patients examined，427 reported abdominal pain from CP during the year before enrolment and the pattern（i.e.constant vs.intermittent pain）and severity of pain were independent of morphological changes.
Diffusion weighted imaging with MR imaging，whichcan provide information of atrophy，ductal pathology and microstructure of the tissue，was applied in a study by Frøkjær et al.In this study，the association between pathological imaging and pain came to the same result in agreement with the aforementioned study but morphological changes were associated with pancreatic function（Balci et al.2009；Frokjaer et al.2013）.
Taken together，pancreatic morphology is not associated with pain in CP and，as such，the rationale for invasive treatment solely based on the results of imaging is questionable.