Pain in pancreatic cancer: does drug treatment still play a role?

Disabling pain together with cachexia is the most important symptom in patients with pancreatic cancer. Abdominal pain is a common debilitating symptom quickly leading to deterioration of the quality of life and performance status [1]. Although only 30-40% of patients report moderate to severe pain at the time of diagnosis, more than 80-90% of them with advanced disease experience severe pain before death [2]. Pain is generally transmitted through the celiac plexus which harbors sympathetic fibers carrying nociceptive information from the pancreas and surrounding organs. More infrequently, pain results from pancreatic duct obstruction and associated pancreatitis; this type of pain usually appears after meals, thus increasing the continuous pain related to the infiltration of the peripancreatic nervous plexus [3]. Management of pancreatic cancer-related pain is difficult, representing one of the main aspects of comprehensive management of the disease and should be started as soon as possible. In planning effective treatment, it is important to assess the nature of each type of pain (somatic, visceral, neuropathic or mixed). For example, patients with marked anxiety and/or depression may need at least 2-4 weeks of antidepressants to obtain optimum results, whichever analgesic treatment is chosen. Assessment of pain includes its quantification with a specific pain-scorescale and periodic reassessment is a continuing necessity as old pain may get worse and new types may develop. Since fewer than 20% of patients present with localized, potentially curable tumors, pain treatment still remains the mainstay of “best supportive care”, very often the only viable strategy in daily clinical practice [1]. Relief of pain usually requires a multimodality approach including: a) modification of the pathologic process, b) interruption of the pain pathways and c) elevation of the pain threshold. Analgesia can be achieved through the utilization of drugs (pain pharmacotherapy) or by means of procedures leading to neurolysis of the celiac plexus. In recent decades, great emphasis has been placed on celiac ganglion neurolytic block, as some studies have shown that, in inoperable pancreatic cancer, pain relief with analgesic drugs is often inadequate [4]. In synthesis, neurolysis can be achieved by means of four techniques: 1) intraoperative chemical splanchnicectomy, 2) percutaneous (computed tomography or ultrasoundguided) block, 3) endosonographically-guided block and 4) thoracoscopic splanchnicectomy [5]. Of course, all these procedures are invasive with full relief of pain obtained in only a small percentage of patients. On the contrary, a decrease in opioid dosages is achieved in almost 50% of patients and is effective for 3-4 months [6]. Controversy also exists as regards the timing of the neurolytic block, i.e. late (only after full failure of major analgesics) or early (before the onset of incapacitating pain) [4, 5]. Therefore, standardization of these alternatives to analgesic drug treatment is still lacking and the indication often remains more related to the presence of local expertise and feasibility than to objective requirements. These difficulties in attempting to interrupt the anatomical pain pathways give utmost importance to the need for elevation of the pain threshold. Concerning this, the utilization of analgesics is simply one way of elevating the patient’s pain threshold, thus reducing the perception of pain.