Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer with a considerable symptom burden and poor prognosis. Focus on maintaining patients’ quality of life and pain control is therefore paramount. Pain management in MPM is complex due to its multifactorial etiology resulting from direct tumor infiltration of the surrounding soft tissue, bone, and encasement of the intercostal nerves. A variety of treatment modalities, including pharmacological and non-pharmacological options, are often required to achieve adequate pain control in this challenging disease. This review article examines the current challenges and solutions available for pain management in MPM.


Keywords: malignant, pleural, mesothelioma, pain, radiotherapy


INTRODUCTION

Malignant pleural mesothelioma (MPM) is a rare cancer affecting the pleural lining. It has a considerable symptom burden and poor prognosis, with a median life expectancy of 9–14 months from diagnosis.1 Exposure to asbestos, with its long latency period, accounts for the continued increase in incidence seen within the UK.2 Worldwide around 14,200 new cases of MPM are diagnosed each year. Incidence rates vary across the world, with 2,700 new cases diagnosed each year in the UK, an increase of around two-thirds since the 1990s.3 Patients often present with a variety of symptoms including shortness of breath, pain, and cancer cachexia.1 Diagnosis often occurs at an advanced stage of the disease which is refractory to multiple treatment modalities. Focus on quality of life and pain control is therefore paramount to the care of patients with MPM.4

Pain management in MPM is complex and challenging as a consequence of its multifactorial etiology. Patients can experience diffuse, dull, and pleuritic chest pain which characteristically increases in severity with disease progression.5 Pain is initiated not only by tumor infiltration but also as a result of investigation and management of the disease.6 To achieve optimum pain control adequate assessment and understanding of this mixed pathophysiology is key to the selection of appropriate pain management. This article will explore the pathophysiology of pain in MPM and will describe the various treatments that are available to try and help alleviate pain in this condition.

PATHOPHYSIOLOGY

Pain is defined “as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”7 Cancer pain is often mixed in origin being both nociceptive and neuropathic pain. Nociceptive pain includes somatic and visceral pain from innervated skin, soft tissue, bone, and organs, while somatic pain is experienced as a localized dull or ache sensation visceral pain, is deep and squeezing, with poor localization, and can involve referred pain to other sites.8 Direct stimulation or increased sensitivity from an inflammation process, such as cancer, activates nociceptive receptors resulting in pain.9 Neuropathic pain, alternatively, occurs from an injury affecting the central or peripheral nervous system, such as compression or destruction of the nerve.8 MPM’s often presents with mixed nociceptive–neuropathic pain due to direct infiltration of soft tissue and bone, as well as encasement of the intercostal nerves. Its aggressive nature can lead to major challenges in pain management and has the potential to progression to severe intractable pain.10

PHARMACOLOGICAL MANAGEMENT

Since its publication in 1986, the WHO’s Analgesic Ladder for Cancer Pain Relief, detailed in Figure 1, has remained to be the cornerstone of pharmacological management of cancer pain. It outlines a stepwise approach that has been demonstrated to relieve 80% of cancer pain.11

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