Pharmacological pain management in chronic pancreatitis

Table 1 Recommended risk factor modifications in chronic pancreatitis according to the MANNHEIM criteria

Risk factor	Treatment	Comments
Alcohol	Alcohol cessation	Decrease disease progression and may have beneficial effects on pain
Nicotine	Smoking cessation	Decrease disease progression and may have beneficial effects on pain
Nutritional	No specific recommendations	No prospective data
Hereditary	Endoscopic surveillance	Currently no formal evidence, a prospective trial has been initiated
	Pancreatectomy with autolog stem cell transplantation	Preferred strategy in some United States centers
Efferent duct	Endoscopy or surgical interventions	The benefit of intervention is controversial
Immunological	Steroid treatment	Treatment of autoimmune pancreatitis follows guidelines provided in e.g., Ref. 32
Metabolic	Lipid lowering therapy, parathyroidectomy, etc.	Consider referral to an endocrinologist

Table 2 Treatment of extrapancreatic causes of pain in chronic pancreatitis

	Treatment	Comments
Peptic ulcer	Proton pump inhibitor +/- eradication of H. pylori	Avoid NSAIDs in CP Patients
Pseudocysts	Endoscopic drainage, transcutaneous drainage or surgical drainage	Preferred treatment dependent on pseudocyst localization and morphology
Duodenal obstruction	Endoscopic dilation or surgical therapy	Endoscopic dilation preferred as first line therapy
Bile duct obstruction	Covered metal stent or plastic stent	Controversial, one study found no relationship between bile duct obstruction and pain

NSAID: Nonsteroidal anti-inflammatory drugs; CP: Chronic pancreatitis; H. pylori: Helicobacter pylori.

Table 3 Current available pharmacological treatments for pain in chronic pancreatitis

Pain mechanism	Treatment option(s)	Comments	Ref.
Raised levels of CCK	Pancreatic enzyme replacement therapy	Only non-enteric coated enzymes have proven effective	[57-65]
	Somatostatin-analogues	Conflicting results, prolonged release formulations may be of value	[67,68]
Pancreatic inflammation and oxidative stress	Antioxidants	Conflicting results, probably most valuable in tropical calcifying CP	[71,72]
Central sensitisation	Antidepressants (TCA, SSRI, SNRI)	Expert opinion, no clinical data (Ref.)	[2]
	Gabapentinoids (Gabapentin/Pregabalin)	Modest effect on pain in a randomised placebo controlled trial (Pregabalin)	[42]
	Ketamine	Reverses hyperalgesia in an experimental pain study	[54]
Analgesics	Tramadol vs morphine	No difference in pain relief in a randomised controlled trial, fewer side effects on tramadol treatment	[35]
	Fentanyl vs Morphine	No difference in pain relief in a randomised controlled trial	[41]
	Oxycodone vs Morphine	Oxycodone superior to morphine on experimental pain measures	[39]
	ADL 10-0101:KOR agonist	KOR agonist superior to morphine on experimental and clinical pain measures. Limited number of patients (n = 6)	[40]

CCK: Cholecystokinin; CP: Chronic pancreatitis; TCA: Tricyclic antidepressant; SSRI: Selective serotonin reuptake inhibitor; SNRI: Serotonin norepinephrine reuptake inhibitor; KOR: Kappa opioid receptor.