|Year : 2021 | Volume
| Issue : 1 | Page : 1-3
Comeuppance of adult cancer pain in contemporary modern times: The dawn of a new era of understanding
Ashok Kumar Saxena1, Suman Choudhary1, Hammad Usmani2
1 Department of Anaesthesiology and Pain Medicine, University College of Medical Sciences, University of Delhi and GTB Hospital, Delhi, India
2 Professor and Consultant Incharge, Pain clinic, Department of Anaesthesiology, J.N. Medical college, Aligarh Muslim University, Aligarh, India
|Date of Web Publication||27-Apr-2021|
Dr. Ashok Kumar Saxena
Department of Anaesthesiology and Pain Medicine, University College of Medical Sciences, University of Delhi and GTB Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Saxena AK, Choudhary S, Usmani H. Comeuppance of adult cancer pain in contemporary modern times: The dawn of a new era of understanding. Indian J Pain 2021;35:1-3
|How to cite this URL:|
Saxena AK, Choudhary S, Usmani H. Comeuppance of adult cancer pain in contemporary modern times: The dawn of a new era of understanding. Indian J Pain [serial online] 2021 [cited 2021 Sep 24];35:1-3. Available from: https://www.indianjpain.org/text.asp?2021/35/1/1/314695
”We don't have much choice about how we enter the world, but a lot of choices exist related to our exit from the world…….”
In the remarkable history of Hollywood, the leading character of a movie Forrest Gump, comments a famous quotable quote that “Life is like a box of chocolates – you never know what you are going to get.” But in my opinion on cancer pain, an even more quotable quote could have been possibly as “suffering due to cancer pain, is like a box of chocolates – you never know what you are going to get.” Obviously, life seems to explore the ingenious, inventive, imaginative, and insightful pathways by which to terminate itself.
In contemporary, modern times, death's dominance has been dominated by the two unique big Cs, cancer pain, and cardiac pain, to which a third C has been recently added-that is COVID-19. Hence, you know that in a thriller, when the curtain comes down at the end, we surely conclude that the villain (cancer pain) will get his comeuppance and retribution that is taken for granted. Its how he gets it or how we manage cancer pain is what makes a thriller a thriller.
Cancer remains the second most important cause of mortality in India, with about 0.3 million deaths per year. It is well established that in the terminal cancer or advanced stages of cancer, 75%–95% of patients do experience and have to cope up with cancer-related pain and chronic cancer pain syndromes, associated with allodynia or hyperalgesia to warm or cold sensation. A typical exacerbation of cancer pain or breakthrough pain can occur, and its incidence may vary in the cancer literature. In the opinion of Coyle et al., cancer pain was noted to be moderate to severe in intensity in approximately 40%–50% and very severe or excruciating in 25%–30% of advanced cancer patients. Furthermore, in a systematic review of the past 40 years, van den Beuken-van Everdingen et al. concluded that cancer-related pain is frequently prevalent in up to 60% of patients receiving anticancer treatment, and in 90% of those cancer patients with advanced disease.
No doubt cancer pain is absolutely multifaceted and confined to multiple anatomical sites encompassing nociceptive and neuropathic components of cancer pain. Cancers of the breast, lung, and prostate do often metastasize to bone, and in the terminal stages, it predisposes to bone remodeling and consequential bone fractures, that again causes immense excruciating pain and total interference of daily routine activities resulting in significantly compromised quality of life.,,
Another significant entity is chronic persistent postsurgical pain (CPPP) following surgery in cancer patients Saxena et al., in a recent study reported the incidence of 38.1% of CPPP following staging laparotomy for carcinoma of the ovary. They also observed an upregulation and positive correlation between mRNA expression of signal transduction genes (PKA, PKC, and ERK) and Visual Analog Scale score, which reflects its potential role in the pathogenesis of CPPP.
Extreme degree of caution is required to intensively monitor these patients for adverse events of opioids, encompassing opioid-induced hyperalgesia. Clinical trials are underway on the simultaneous use of adjuvants such as selective COX inhibitors, NK1 antagonists, 5HT3 antagonists, and anti-tumor necrosis factor and the anti-nerve growth factor (NGF) drugs, along with opioids, for mitigating the doses of opioids and their adverse effects, inclusive of opioid induced tolerance and opioid-induced hyperalgesia. The NGF antagonist PD90780 interacts with NGF and prevents its bondage and binding to p75NTR (the common neurotrophin receptor)
Pancreatic cancer is the 2nd most common cause of cancer related death and is one the specific example cited for development of neuropathic pain. Recently, Lohse and Brothers suggested that perineural involvement is a dominant salient manifestation of pancreatic cancer, and this subsequently results in the development of neuropathic pain. Moreover, Lohse and Brothers observed that Cisplatin therapy predisposes to the development of axonal neuropathy in the dorsal root ganglion and in the large sensory fibers. This is in addition to the manifestation of therapy-induced mucositis in the gastrointestinal tract, as a consequence of chemotherapy, which ultimately leads to infection-prone ulcers on the buccal mucosa, tongue, lips, and palate. Interestingly, Denk et al. have recently observed that Histone deacetylase (HDAC) inhibitors specific for Class I and Class II HDAC enzymes, delayed the onset and minimized the pain behavior and stress-induced visceral nociception in nociceptive animal models and models of drug-induced peripheral neuropathy. The neurolysis of celiac plexus has also shown satisfactory pain relief in 74% of pancreatic cancer pain patients. Recently, it has been suggested that epigenetic modulation may possibly be a viable option and may offer an ideal channel for the management in pancreatic cancer pain.
In an editorial by Jain PN, the conclusions for the most appropriate candidates for endoscopic ultrasound-guided celiac plexus block (EUS-CPB) were patients with unresectable pancreatic cancer with significant pain that is completely or partially refractory to narcotic pain medications. The EUS-guided celiac plexus neurolysis may provide effective palliation of pancreatic cancer pain in 78%–88% of patients. Moreover, the main observations of a meta-analysis and systematic review by Puli et al. were that with EUS-CPN, 85% patients with pancreatic cancer had good pain relief, and 60% patients had similar good relief and there was no publication bias as judged by “bias indicators” and construction of funnel plots.
There is a recent explosion in the passionate use of cannabinoids (including Cannabis) for pain management, congruent with legalized approval of use of cannabis in 40 countries and 29 states in USA. However, the WHO guidelines for cancer pain management in adults and adolescents reflect that extensive data analysis is required on cannabinoids in the context of cancer pain management.
Exploring the role of Cannabinoids for adult cancer-related pain, Boland et al. in a recent systematic review and meta-analysis concluded that on addition of cannabinoids to opioids there was no reduction in cancer pain. None of the phase III studies had shown any positive result, with cannabinoids. Hence, as based on evidence, cannabinoids cannot be recommended for the management of cancer pain.
Cancer patients can also experience chemotherapy-induced mucositis, chemotherapy-induced musculoskeletal pain and radiation-induced mucositis, cutaneous reactions as dermatitis, and even radiation-induced enteritis. Cancer patients can also suffer from chronic pain after breast surgery. Specific chemotherapeutic agents such as taxanes, platins, bortezomib, and vincristine can also cause chemotherapy-induced peripheral neuropathy (CIPN), and aromatase inhibitors can predispose to diffuse joint pain.
In the opinion of Deng G, the use of integrative medicine therapies in the management of cancer pain is very much supportive, positive, and encouraging. Data from randomized controlled trials indicate the benefits of hypnosis, acupuncture, and music therapy, in the multimodal approach for cancer pain management. The use of other approaches such as mindfulness meditation, yoga, qigong, and massage therapy, and acupressure, may not reduce cancer pain per se but can act as adjuncts in relieving anxiety, depression, and mood changes, associated with cancer pain.
Recently, Swarm et al. have brought out a latest version 3.2019 of National Comprehensive Cancer Network (NCCN) guidelines for adult cancer pain, which have been significantly revised, with a focus on appropriate and safe dosages of opioid analgesics, optimization of nonopioids analgesics and adjuvants, and utilization of nonpharmacologic techniques of cancer pain management. This document describes the pathophysiological classification of cancer pain syndromes, overall pain assessment, treatment of pain crises, current care for cancer pain, and pain in cancer survivors.
The latest NCCN adult cancer pain guidelines recommend that upper abdominal cancer pain patients, who are unable to tolerate opioids or those not getting satisfactory analgesia, should be offered a neurolytic CPB. Another set of NCCN guidelines is encouraging the use of regional infusion analgesics to avoid the kinetics of analgesics to central receptors and thus minimizing the side effects of parenteral opioids. Hence, emphasis is now on intrathecal, epidural, and regional plexus routes. In addition, the NCCN adult cancer pain guidelines recommend the technique of “percutaneous vertebral augmentation” for the management of spinal metastasis of lytic osteoclastic variety and for the management of compression fracture of the vertebrae. This vertebral augmentation minimizes the pain while at the same time ensuring the mechanical stability.,
The highlights of the NCCN adult cancer pain guidelines also include utilization of radiofrequency ablation and ultrasound ablation, for pain management in various bone lesions., These NCCN guidelines also lay emphasis on various neurostimulation procedures for the management of pain in CIPN and complex regional pain syndrome.
Finally, the ultimate message of these latest NCCN adult cancer pain guidelines is that these interventions should be encouraged in cancer pain patients, with a reasonable life expectancy prediction, having excluded bleeding tendencies, and localized infections. Last but not the least, these NCCN guidelines suggest that cancer pain can be alleviated in large number of patients, if there is a systematic application of the presenting algorithms, and if these are intensively supervised, monitored, and personalized and individualized to the specific requirements of each individual cancer pain patient.
An introspection is required, as when these cancer patients are told that they have limited period of few weeks to few months to survive, then you can imagine that what kind of thoughts, would rush into their mind. This is where these cancer pain patients need guidance on meditation and psychosocial counseling, conveying them that superior to the senses is the mind, and superior to the mind is the intellect, and one who is superior even to the intellect, is the self or self-control.
We wholeheartedly thank and acknowledge the contributions of the authors of cancer pain in this particular issue, for their excellent write-ups, convincing and comprehensive analysis and evidence, and for proposing a roadmap in the forward direction. Evidently, there is an essential need for greater diverse research to replicate the findings for better understanding. We are absolutely confident that these write ups are going to have tangible benefits for cancer patients suffering from cancer pain.
| References|| |
Jha P, Gajalakshmi V, Gupta PC, Kumar R, Mony P, Dhingra N, et al
. Prospective study of one million deaths in India: Rationale, design, and validation results. PLoS Med 2006;3:e18.
Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP. Molecular mechanisms of cancer pain. Nat Rev Cancer 2002;2:201-9.
Svendsen KB, Andersen S, Arnason S, Arnér S, Breivik H, Heiskanen T, et al
. Breakthrough pain in malignant and non-malignant diseases: A review of prevalence, characteristics and mechanisms. Eur J Pain 2005;9:195-206.
Coyle N, Adelhardt J, Foley KM, Portenoy RK. Character of terminal illness in the advanced cancer patient: Pain and other symptoms during the last four weeks of life. J Pain Symptom Manage 1990;5:83-93.
van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: A systematic review of the past 40 years. Ann Oncol 2007;18:1437-49.
American Cancer Society. Cancer facts and Figures 2008. Atlanta: American Cancer Society; 2008.
Saxena AK, Chilkoti GT, Chopra AK, Banerjee BD, Sharma T. Chronic persistent postsurgical pain following staging laparotomy for carcinoma of ovary and its relationship to signal transduction genes. Korean J Pain 2016;29:239-48.
Lohse I, Brothers SP. Pathogenesis and treatment of pancreatic cancer related pain. Anticancer Res 2020;40:1789-96.
Denk F, Huang W, Sidders B, Bithell A, Crow M, Grist J, et al
. HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. Pain 2013;154:1668-79.
Comlek S. Pain control with splanchnic neurolysis in pancreatic cancer patients unresponsive to celiac plexus neurolysis. J Pain Res 2020;13:2023-1.
Jain PN. Endoscopic ultrasound-guided celiac plexus block in pancreatic cancer pain: A never innovative imaging technique for pain relief. Indian J Pain 2010;24:116.
Gunaratnam NT, Sarma AV, Norton ID, Wiersema MJ. A prospective study of EUS-guided celiac plexus neurolysis for pancreatic cancer pain. Gastrointest Endosc 2001;54:316-24.
Puli SR, Reddy JB, Bechtold ML, Antillon MR, Brugge WR. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain: A meta-analysis and systematic review. Dig Dis Sci 2009;54:2330-7.
Godlee F. Medical cannabis on the NHS. BMJ 2018;362.doi:10.1136/bmj.k3357.
World Health Organization. WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. Geneva: World Health Organization; 2018.
Boland EG, Bennett MI, Allgar V, Boland JW. Cannabinoids for adult cancer – Related pain: Systematic review and meta- analysis. BMJ Supp Pall Care 2020;10;14-24.
Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al
. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453-61.
Saibil S, Fitzgerald B, Freedman OC, Amir E, Napolskikh J, Salvo N, et al
. Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: A retrospective, outcomes-based survey. Curr Oncol 2010;17:42-7.
Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and chronic cutaneous reactions to ionizing radiation therapy. Dermatol Ther (Heidelb) 2016;6:185-206.
Harb AH, Abou Fadel C, Sharara AI. Radiation enteritis. Curr Gastroenterol Rep 2014;16:383.
Fassoulaki A, Melemeni A, Staikou C, Triga A, Sarantopoulos C. Acute postoperative pain predicts chronic pain and long-term analgesic requirements after breast surgery for cancer. Acta Anaesthesiol Belg 2008;59:241-8.
Gewandter JS, Freeman R, Kitt RA, Cavaletti G, Gauthier LR, McDermott MP, et al.
Chemotherapy-induced peripheral neuropathy clinical trials: Review and recommendations. Neurology 2017;89:859-69.
Deng G. Integrative medicine therapies for pain management in cancer patients. Cancer J 2019;25:343-8.
Swarm RA, Paice JA, Anghelescu DL, Are M, Bruce JY, Buga S, et al
. Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019;17:977-1007.
Zheng S, He L, Yang X, Li X, Yang Z. Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies: A prospective cohort study. Medicine (Baltimore) 2017;96:e6354.
Tancioni F, Lorenzetti MA, Navarria P, Pessina F, Draghi R, Pedrazzoli P, et al
. Percutaneous vertebral augmentation in metastatic disease: State of the art. J Support Oncol 2011;9:4-10.
Berenson J, Pflugmacher R, Jarzem P, Zonder J, Schechtman K, Tillman JB, et al
. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: A multicentre, randomised controlled trial. Lancet Oncol 2011;12:225-35.
Napoli A, Anzidei M, Marincola BC, Brachetti G, Ciolina F, Cartocci G, et al
. Primary pain palliation and local tumor control in bone metastases treated with magnetic resonance-guided focused ultrasound. Invest Radiol 2013;48:351-8.
Dupuy DE, Liu D, Hartfeil D, Hanna L, Blume JD, Ahrar K, et al
. Percutaneous radiofrequency ablation of painful osseous metastases: A multicenter American College of Radiology Imaging Network trial. Cancer 2010;116:989-97.
Flagg A 2nd
, McGreevy K, Williams K. Spinal cord stimulation in the treatment of cancer-related pain: “Back to the origins.” Curr Pain Headache Rep 2012;16:343-9.