Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments

Abstract

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

Mast cell‐neural interactions contribute to pain and itch

“…Several other processes have been recognized including tunneling nanotubes (TNT), physical extension via pseudopodia‐like structures, and extracellular trap formation, which may allow for increased interaction of mast cells with vasculature, nervous system, and immune cells, described in detail below. Therefore, mast cells exhibit extraordinary complexity and contribute to diverse functions . This review will examine the interactions of mast cells with the central and peripheral neural systems, pathophysiological mechanisms, and therapeutic targets to treat pain and pruritus.…”

“…Therefore, mast cells exhibit extraordinary complexity and contribute to diverse functions. 1,[3][4][5][8][9][10]12,16,[23][24][25] This review will examine the interactions of mast cells with the central and peripheral neural systems, pathophysiological mechanisms, and therapeutic targets to treat pain and pruritus.…”

“…Mast cells that become extremely sensitive can lead to well‐known pathologic condition, allergy, and anaphylaxis. In addition to defense against environmental stimuli, mast cells are also sensitive to the endogenous microenvironment and therefore contribute to many biological and pathological processes including vascular physiology, pain, itch, and cancer . Increasing evidence suggests that mast cells contribute to various pathologies via their interactions with the vasculature and CNS.…”

Patterns and predictors of end‐of‐life care in older patients with pancreatic cancer

“…Effective end‐of‐life care is essential for patients with cancer, and discussions surrounding high‐quality end‐of‐life care include considerations about appropriate use of treatment and timely use of hospice services (ideally prior to the final week of life) . Optimizing end‐of‐life care is particularly important for patients with PDAC, as they often experience substantial symptom burden including pain, fatigue, poor appetite, and nausea . Research has demonstrated that during the final months of life, patients with PDAC can experience increased symptom burden and decreased overall quality of life .…”

Chronic pain syndrome in patients with pancreatic cancer: individual therapy and its pathogenetic background

“…As a rule, it is accompanied by a pharmacy-resistant clinical manifestation which is often associated not only with tolerance, but also with the appearance of numerous adverse effects of opioid therapy [8]. Pain syndrome in advanced pancreatic cancer is registered in 80% of patients along with abdominal distension, belching, heartburn, abnormal stool, cancer-related weakness and weight loss [9], and it is associated with decreased survival [10]. Only 30-40% of patients with pancreatic cancer have moderate or severe pain.…”