Best Practices for Chronic Pancreatitis Pain Management: A Comprehensive Evidence-Based Review

Introduction

Chronic pancreatitis (CP) is a chronic inflammatory condition of the pancreatic tissue, attributed to genetic, environmental, and/or other risk factors, which may lead to atrophy of pancreatic acini and impaired pancreatic function.¹ Despite notable declines in the morbidity and mortality rates of pancreatitis in China over the past two decades, the healthcare burden remains significant due to the country’s large population.² Abdominal pain, one of the most common clinical symptoms of CP, affects 60–94% of individuals with the condition and significantly diminishes their quality of life.^3,4 This pain may stem from increased pressure in the pancreatic duct, interstitial hypertension, ischemia, neurogenic mechanisms, and other contributing factors.⁵ Several pain management strategies have been proposed in various guidelines,^6,7 including changes in lifestyle, further use of analgesics, and surgical or endoscopic treatments.

Alcohol consumption is a risk factor for the progression of acute alcoholic pancreatitis to CP, and abstaining from alcohol can prevent the recurrence of acute pancreatitis and its progression to CP. A diet low in fat is effective for patients with pain in the compensated phase; nonsteroidal anti-inflammatory drugs (NSAIDs) are the first choice for pain relief in CP patients, with opioid medications used if NSAIDs are ineffective. Endoscopic treatment is used for patients with pain due to pancreatic duct obstruction, and extracorporeal shock wave lithotripsy (ESWL), endoscopic treatment, and surgical intervention are options for the treatment of pancreatic stones.The current guidelines for pain management in CP patients face several issues, including a lack of standardized pain assessment tools, inconsistencies in recommendations between different regions or organizations, and some evidence being of low quality. Due to the inconsistencies or insufficient evidence supporting the guidelines, clinicians may face difficulties when devising treatment plans. They need to choose between different treatment options that may carry varying risks and benefits. This uncertainty could lead to anxiety or discomfort for physicians when making decisions. Patients may not receive the best treatment plans, which could result in poor pain control, decreased quality of life, and waste of medical resources. Moreover, inconsistent recommendations may also lead to misunderstandings and dissatisfaction between patients and their families, further exacerbating the tension in doctor-patient relationships.Therefore, this study aims to synthesize the best available evidence on pain management in CP through a systematic search, quality evaluation, and evidence extraction, offering clinical practitioners valuable insights for optimizing pain management strategies.

Data and Methods

Formulation of Evidence-Based Questions

The evidence-based questions for this study were developed using the PIPOST framework:⁸

• P (population): Individuals diagnosed with chronic pancreatitis
• I (intervention): Pain management strategies
• P (professional): Medical and healthcare personnel
• O (outcome): Measures such as pain scores, quality of life (QOL), and length of hospital stay
• S (setting): Health and medical institutions
• T (type of evidence): Clinical practice guidelines, expert consensus statements, systematic reviews, and evidence summaries.

Search Strategy

A comprehensive literature search related to pain management in CP was conducted using the “6S” evidence model.⁹ The search terms in English included “Pancreatitis/Pancreatitis, Chronic/Chronic Pancreatitis/Chronic Pancreatitides/Pancreatitides, Chronic”, “Pain Management/Management, Pain/Managements, Pain/Pain Managements”, and “guideline/recommended practice/best practice/evidence summary/systematic review/Meta-analysis”. The databases searched included: (1) Clinical decision-making systems such as UpToDate; (2) Guideline networks, including the Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), and guide.medlive.cn; and (3) Comprehensive literature databases such as Chinese Biomedical Literature Service System, China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, Embase, and the Cochrane Library. The search encompassed all relevant literature up to October 15, 2023. For instance, the PubMed search strategy was structured as follows:

#1 (Pancreatitis [Title/Abstract]) OR (Pancreatitis, Chronic [Title/Abstract]) OR (Chronic Pancreatitis [Title/Abstract]) OR (Chronic Pancreatitides[Title/Abstract]) OR (Pancreatitides, Chronic [Title/Abstract])

#2 (Pain Management [Title/Abstract]) OR (Management, Pain [Title/Abstract]) OR (Managements, Pain [Title/Abstract]) OR (Pain Managements [Title/Abstract])

#3 (guideline [Title/Abstract]) OR (recommended practice [Title/Abstract]) OR (best practice [Title/Abstract]) OR (evidence summary [Title/Abstract]) OR (systematic review [Title/Abstract]) OR (Meta analysis [Title/Abstract])

#4 #1 AND #2 AND #3

Inclusion and Exclusion Criteria

The inclusion criteria were as follows: (1) studies involving individuals with CP; (2) studies focusing on pain management; (3) outcomes of interest, including pain scores, QOL, and length of hospital stay; (4) article types limited to guidelines, best practices, evidence summaries, systematic reviews, and meta-analysis published in both China and international literature; and (5) articles available in Chinese and English.

Exclusion criteria were as follows: (1) study protocols or plans; (2) guidelines, systematic reviews, and expert consensus documents that had been updated or contained redundant content, as well as original research already incorporated into the aforementioned article types; and (3) articles that failed to meet quality evaluation standards.

Article Screening and Data Extraction

The article screening process was carried out independently by two assessors. Initially, titles and abstracts of potentially relevant articles were briefly reviewed, followed by a full-text assessment of articles deemed eligible. In cases of disagreement, a third assessor was consulted to resolve discrepancies and determine article inclusion. The information extracted from the included articles was managed using Excel and primarily comprised the title, article source, publication date, and article type.

Quality Evaluation of Articles

The quality of the included articles was assessed using standardized tools. Clinical practice guidelines were evaluated using the AGREE II tool,¹⁰ while expert consensus documents were assessed according to the Expert Consensus Evaluation Standard of the JBI Center for Evidence-Based Healthcare.¹¹ Clinical decisions were evaluated using the Critical Appraisal for Summaries of Evidence (CASE) tool.¹² The quality of systematic reviews was evaluated using the AMATAR 2 tool.¹³

Evidence Summary and Grading

All included articles were thoroughly reviewed, and the evidence was graded using the Evidence Grading System of the JBI Center for Evidence-Based Healthcare.¹⁴ The level of recommendation was determined based on the FAME (Feasibility, Appropriateness, Meaningfulness, Effectiveness) framework.¹⁴

Results

Flowchart and Article Screening Results

The initial search identified 440 articles. After removing duplicates and articles that did not meet the inclusion criteria, 21 articles were selected for inclusion. These consisted of four guidelines,^6,7,15,16 two expert consensus documents,^17,18 one clinical decision,¹⁹ and 14 systematic reviews.^20–33 The article screening process is illustrated in Figure 1. The general information of the included articles is summarized in Table 1.

Table 1 General Information of Included Articles

Figure 1 Flowchart of Article Screening.

Basic Features of Included Articles

The basic characteristics of the included articles are shown in Table 1. The included articles were published between 2015 and 2023, with the majority being published in 2021, accounting for 33.3% of the total.

Quality Evaluation Results

Evaluation of Guidelines

Among the four guidelines, two were assigned a recommendation level of A indicating high quality,^7,16 while the remaining two were assigned a level B.^6,15 These results are presented in Table 2.

Table 2 Quality Evaluation Results of Clinical Guidelines

Evaluation of Expert Consensus Statements

According to the Expert Consensus Evaluation Standard of the JBI Center for Evidence-Based Healthcare (2016 Edition), both expert consensus documents were evaluated positively, with all items receiving a “yes” rating.^17,18 This indicates that the expert consensus documents were of high quality and were thus included in the study.

Evaluation of Clinical Decisions

The quality assessment of the clinical decision obtained from UpToDate indicated that items 4, 5, and 9 were rated as “unclear”, while the remaining items received a “yes” rating.¹⁹ Despite these uncertainties, the clinical decision was deemed to be of high quality and was included for further analysis.

Evaluation of Systematic Reviews

Among the 14 systematic reviews assessed,^20–33 the studies by Tringali et al,²¹ Siddappa et al²⁵ and Mendieta et al,²⁶ were rated as “grade A”, indicating high quality, with all evaluation criteria receiving a “yes” rating. Studies by Hughes et al,²³ Bhullar et al,²⁴ Sofi et al,²⁷ and Kempeneers et al³⁰ were rated as “grade B” due to receiving a “no” rating on item 1 (“Is a preliminary plan provided?”) and 4 (“Is the publication status, such as grey literature, considered in the inclusion criteria?”), while the remaining items were rated “yes”. Other systematic reviews were also rated as “grade B” due to “no” ratings for items 1, 4, and 11 (“Is the conflict of interest reported?”),^{20,22,28,29,31–33} though other items were rated “yes”. Despite these limitations, all systematic reviews were considered of sufficient quality for inclusion.

Evidence Summary

The evidence extraction and integration process identified seven categories of treatment for pain management for CP. These categories include pain evaluation, drug intervention, endoscopic treatment, surgical treatment, TCM treatment, other therapeutic modalities, and treatment for special populations. A total of 19 pieces of evidence were identified, with 11 classified as recommendation level A and eight as recommendation level B, as shown in Table 3.

Table 3 Summary of Evidence Results

Discussion

Abdominal pain is one of the common clinical symptoms of CP, with many influencing factors, such as the state of the pancreas (acute or chronic inflammation, pancreatic duct obstruction and/or stenosis caused by stones), peripancreatic structures (common bile duct stenosis, gastric outlet or duodenal obstruction), and/or local complications (eg, pseudocysts), and patient-related factors (psychosocial, comorbidities).³⁴ Abdominal pain can occur at the onset or during the course of the disease, but some patients still have pain symptoms after 10 years or more,⁴ and the intensity and frequency of pain attacks significantly affect the patient’s quality of life and psychological state.³⁵ Therefore, medical personnel need to pay attention to the assessment and treatment of pain in CP patients.

It is important to note that pain in CP patients is a complex sensory experience with many influencing factors. Assessment should consider the variability in clinical presentation and its impact on the patient’s quality of life and mental health. A comprehensive and accurate assessment can make clinical pain management easier, more accurately record treatment responses and outcomes, and improve the pain experience of CP patients. Among the pain assessment tools for CP patients, only a few questionnaires have been tested for all validity dimensions. In the pain assessment tools for CP patients, only COMPAT has been fully validated. Additionally, when assessment tools are used in clinical or research settings, translating questionnaires is also a challenge. When questionnaires are translated into another language, key information from the questionnaire may be lost, which can also reduce the reliability of research results when comparing them internationally. Currently, only the brief pain inventory(BPI) and McGill pain questionnaire(MPQ), two multidimensional pain assessment tools, have been clinically validated after being translated into multiple languages. The lack of standardized and effective pain assessment tools for CP poses difficulties for clinical treatment and research.³⁴ Therefore, there is an urgent need to develop precise and widely applicable pain assessment tools for CP patients, which would not only benefit CP patients but also serve as a template for the symptom assessment of pain in other gastrointestinal diseases.

Additionally, the treatment of CP is a comprehensive, multidisciplinary approach, and both domestic and international guidelines mention a stepwise treatment method to progressively address the pain of CP patients.^6,7 All CP patients are advised to quit smoking and abstain from alcohol, and it is also recommended to improve their dietary structure. For patients without obstruction, medical treatment is suggested first, along with small, frequent meals and a low-fat diet.⁷ The use of pain medication follows the WHO’s three-step analgesic ladder, starting with weak analgesics and gradually moving to stronger ones, beginning with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen, then introducing weak opioids, and finally resorting to strong opioid analgesics. For patients with exocrine insufficiency, systematic reviews have indicated that oral pancreatic enzyme preparations can improve the absorption of fats and fat-soluble vitamins, alleviating symptoms of steatorrhea and other abdominal symptoms.⁷ Approximately 30–60% of CP patients with refractory pain treated with medication require invasive surgery, such as endoscopic intervention or surgery. The most common causes of refractory pain in CP patients are obstruction of the main pancreatic duct (caused by stones or stenosis), biliary obstruction, and pancreatic pseudocysts.³⁴ The main purpose of endoscopic treatment for CP patients is to decompress and place drainage tubes, remove stones to relieve pain, and endoscopic procedures include stent implantation and lithotripsy.⁷ When endoscopic intervention and conservative treatment are ineffective, surgical treatment is considered, with common surgical procedures including longitudinal pancreaticojejunostomy, various types of pancreatic head resections, and resections of the body and tail of the pancreas. Several systematic reviews have pointed out that early surgical intervention results in significantly better postoperative pain relief and improved quality of life compared to early endoscopic treatment for CP patients.^23,26,30 Furthermore, behavioral interventions should be part of the multidisciplinary approach to chronic pain management, especially when psychological issues arise, including cognitive-behavioral therapy, mindfulness techniques, and hypnosis.³⁶ Finally, for CP patients with refractory chronic pain unresponsive to the aforementioned treatments, options such as pancreatic islet autotransplantation, spinal cord stimulation, and celiac plexus block may be considered.

This study systematically reviews the literature on pain management in patients with CP, evaluates the quality of included literature, and integrates evidence extraction to form 19 pieces of evidence across 7 categories: pain assessment, pharmacological interventions, endoscopic treatments, surgical treatments, traditional Chinese medicine treatments, other treatments, and treatments for special populations, providing a reference for clinical practice. However, this study still has limitations, including insufficient comprehensiveness and representativeness of the evidence, timeliness and applicability of the evidence, and challenges in dissemination and implementation. Future research can build on this foundation to conduct more exploration, continuously supplementing or replacing the evidence summary results.

Conclusion

In conclusion, this study consolidates the best available evidence for the management of pain in CP, providing a foundation for evidence-based clinical practice. However, the selection of optimal interventions in clinical settings should be tailored to each patients’ clinical condition, preferences, and the resources available at healthcare institutions, with the goal of improving both pain management and overall quality of life.This study has some limitations, fails to include more latest research data, and the latest research progress can be discussed in the future to enhance its timeliness and prospective.