Behind the Book

In spring 2010, we took the opportunity to ask the editors for their insights on cancer pain treatment.
Q: What sets this book apart from other texts about cancer?
A: Cancer Pain: From Molecules to Suffering is unique in that it addresses the most current research related to cancer pain, presented by noted international experts in the field. Each chapter addresses current work along with clinical implications and research that is needed. It is required reading for basic and clinical scientists working in the field, along with health care professionals who care for these patients.
Q: What are some of the latest breakthroughs in understanding the mechanisms of cancer pain?
A: In the past few years there have been extraordinary breakthroughs in our understanding of the mechanisms of cancer-related pain. New findings regarding the underlying neurobiology of malignant bone pain by Patrick Mantyh and his collaborators have changed the way we understand and treat pain due to primary or metastatic bone lesions. Several investigators, notably Gary Bennett, Jon Levine, and Patrick Dougherty, are exploring the neuronal changes underlying chemotherapy-induced painful peripheral neuropathy. This important work has highlighted the role of cancer treatment as a serious cause of persistent pain. Furthermore, it is leading to strategies that might one day be employed in the clinic to prevent this type of pain, allowing patients to complete potentially curative therapy and improving their quality of life.
Q: Are opioids still the mainstay of cancer pain treatment?
A: Opioids remain crucial to the management of cancer-related pain; however, there is now greater appreciation for the need to employ multimodal therapies. These include nonopioid drugs (nonsteroidal anti-inflammatory drugs and acetaminophen/paracetamol) and adjunctive agents (e.g., anticonvulsants and antidepressants for neuropathic pain), along with newer therapies that are currently under investigation. Furthermore, the role of disease-modifying therapies remains essential, including radiotherapy, chemotherapy, biological treatments, interventional approaches, and other techniques.
Q: How might current insights into the pharmacology of opioid tolerance be applied to the clinical setting?
A: Much more research is needed to better understand opioid tolerance. Currently, there are no randomized controlled trials in humans that explore the rate of tolerance development with opioid administration. It is difficult to differentiate tolerance from disease progression and changes in absorption or elimination of drugs that may be responsible for the need for increasing doses of an opioid. One excellent example is the recent finding that cachexia results in lower plasma levels of fentanyl when administered transdermally. Additionally, strategies to prevent or reduce opioid tolerance may be found in the future through activation of delta-opioid receptors or other targets. Many drugs that are already available still need to be studied in the clinic. These include the NMDA-receptor antagonists ketamine and memantine.
Q: Do you see new options for cancer pain treatment on the horizon?
A: As the underlying mechanisms of cancer pain are unraveled, new treatments are being designed to target these mechanisms. Examples include anti-nerve growth factor (NGF) monoclonal antibodies, which bind to tyrosine kinase receptor A (TrkA) on sensory neurons, reducing activation of nociceptors after noxious stimulation. Another example is the reduction of osteoclast activity by osteoprotegerin ligand (OPG) to reduce malignant bone pain. Many more compounds are currently in development.
Q: What are some of the difficulties in designing clinical trials in cancer patients?
A: Research design issues in cancer pain are critical. Starting with the laboratory, the models employed in animals must accurately predict the experience of patients with malignancy. Designing clinical trials in cancer-related pain can be complicated by disease progression, by the potentially confounding effect of concomitant cancer therapies, and by the heterogeneity of cancer pain syndromes. Conducting these trials can be like shooting at a moving target. Yet there are strategies that can ensure that cancer pain research is designed to answer the most crucial questions. Collaboration between basic scientists and clinicians is vital. The development of international collaborative groups will help with subject accrual and generalizability of findings. Ethical aspects are also particularly important when studying very ill patients. However, most cancer patients are willing to advance pain research by participating in clinical studies. It is a well-known fact that patients who participate in clinical trials do better than those who do not.
Q: Do curative therapies such as radiation and chemotherapy increase or decrease the cancer patient's risk of pain?
A: Disease-modifying therapies such as radiation therapy and chemotherapy can have a significant pain-relieving effect. Radiotherapy has been shown to be very effective in the alleviation of pain due to bone metastases. However, there is also the potential for chronic pain syndromes to occur as a result of cancer treatment. Chemotherapy-induced painful peripheral neuropathy is increasing in prevalence as more neurotoxic agents have been introduced. Plexopathies from radiation can lead to long-term neuropathic pain syndromes. Graft versus host disease is a complex syndrome resulting from stem cell transplant that can lead to severe pain. More research is needed to understand these complications and strategies to prevent or treat the resultant pain.
Q: What are some of the ways in which cancer pain treatment can be tailored to the individual patient?
A: By taking each cancer patient as an individual regarding the disease, pain characteristics, psychosocial factors, and pharmacogenetics.
Q: How can we overcome some of the obstacles to worldwide accessibility to cancer pain relief?
A: Obstacles to global relief of cancer pain center around access issues. Lack of access to clinicians who are educated about pain assessment and management is a significant barrier in both developed and developing worlds. In the developing world, limited availability of medications, particularly opioids, precludes good cancer pain control. Educational efforts can begin to address some of the knowledge deficits. Organizations such as IASP can work with governments and other regulatory bodies to develop policies that will reduce impediments to opioid availability.
Q: Does the book contain any new insights into psychological issues that may affect patients with cancer?
A: The psychological context of cancer pain will greatly affect the entire experience. The role of anxiety, helplessness, catastrophizing, and other states may have a neural substrate. Extraordinary work is being conducted to teach patients and families coping skills to improve self-efficacy. More work is clearly needed in this area, and strategies for dissemination of these strategies into the clinical setting must be encouraged.
Q: Any final comments?
A: We hope that this research symposium and book will inspire more research in cancer pain that combines basic and clinical sciences and also involves many centers globally.