2.1　Analgesics

Analgesics are the firstline medical therapy of pain.According to the“pain relief ladder”provided by the WHO，analgesics are typically titrated until obtaining pain relief，but in some situations a top-down approach or combinant medication may also be useful.

Strong opioids，such as morphine，mainly exert their analgesic effects in the central nervous system through different opioid receptors including the p-receptor，8-receptor and the x-receptor（Olesen et al.2013a）.Different opioids have different analgesic effect.Oxycodone was shown to attenuate experimental visceral pain better than morphine in CP patients（Staahl et al.2007）.Opioids can be administrated either orally or transdermally.Transdermal fentanyl might be useful for symptom control in appropriate dose but it is not the ideal first-choice（Niemann et al.2000）.To some extent，tolerance，opioid induced hyperalgesia and narcotic bowel may cause opiate failure and themselves can also result in chronic abdominal pain（Moran et al.2015）.

Cyclooxygenase（COX）is a key enzyme in the synthesis of prostaglandins（PGs）from arachidonic acid leading to pain and inflammation（Bai et al.2012）.Paracetamol（N-acetylpaminophenol）is one of the analgesics recommended for the treatment of mild or moderate pain in CP.Several studies on alcoholic patients proved that the drug can be safely administered at a single dose of 1 g and daily dose of 4 g/24 h while excess dosage would cause hepatic cell damage.CP patients with diagnosed paracematol poisoning may be at high risk of attacked by acute pancreatitis（Siepsiak et al.2016）.(https://www.daowen.com)

While tramadol has a similar efficacy as morphine in equivalent dose，it seems to have a better side-effect profile（Majumder and Chari 2016）.In a double blinded randomized trial，25 patients with severe chronic pancreatitis were required to take tramadol or morphine for 5 days.Finally less patients on tramadol reported gastrointestinal interference and pain relieving effect of tramadol tended to be beter than morphine on day 4（Sharma et al.2014）.

Giventhe neuropathological etiology of pain，the role of neuromodulators in the management of chronic pain has gained great attention.Tricyclic antidepressants（TCAs）and gabaergics，which can modulate the spinal processing of nociceptive signals，are practically being used to control neurogenic pain（Moran et al.2015）.Pregabalin has been applied in various chronic pain disorders and proved to be effective，including post herpetic neuralgia，diabetic neuropathy and neutropathic pain of central origin（Olesen et al.2013b）.A hypothesis-generating study was conduct to provide the evidence that pain relief with pregabalin was associated with increased endogenous inhibitory modulation and antihyperalgesic effects（Bouwense et al.2015）.Side effects were reported more in pregabalin compared to placebo（Gurusamy et al.2016b）.