Oncological pain

Translation- Evidence Based Acupuncture Evidence Summary – Acupuncture for the therapeutic treatment of cancer pain

Pain is very common in former cancer patients and can be caused by cancer cells invading organs, soft tissues (nerves and blood vessels), or bones. This pain can also arise from medical treatments for cancer, including chemotherapy, radiotherapy, hormone therapy, and surgery. Multiple areas can be affected, and multiple mechanisms can be the cause of inflammatory, neuropathic, ischemic, and compression pain. Bone pain caused by metastases is often particularly severe, relentless, and difficult to control. Patients with bone pain require high-dose pain medication. This medication often has unwanted side effects [1].

Moderate to severe pain is experienced by 40% of individuals with early or intermediate stage cancer and by 90% of individuals with advanced cancer. 70% of all patients with oncologic pain experience insufficient pain relief, leading to a decrease in quality of life both physically and psychologically [2].

ACUPUNCTURE FOR ONCOLOGICAL PAIN: CLINICAL EVIDENCE
In a comparative literature review in 2017, a potential positive effect of acupuncture was found in the treatment of oncological pain [3]. This review included two systematic studies. The oldest study was not suitable for drawing firm conclusions due to the small study group and clinical differences in the patients treated. The most recent study included 36 studies and over 2200 randomized patients. A moderately positive effect of acupuncture was found for oncological pain, and it was concluded that 'acupuncture is effective in relieving oncological pain, particularly in malignancy-related and surgery-induced pain' [4]. Although this literature study does not make a statement about the potential risks associated with acupuncture treatment, earlier studies indicate that acupuncture is a feasible and safe treatment [5],[6]. Acupuncture can be successfully used to treat cancer patients for symptom management, due to the low risks associated with its use [7].

ACUPUNCTURE IN ONCOLOGICAL PAIN: THE BIOLOGICAL MECHANISMS
The mechanism of action by which acupuncture provides pain relief in the treatment of oncological pain is presumed to be similar to that in the treatment of other painful conditions, whether the pain is acute or chronic. The effectiveness of acupuncture in treating pain has been extensively studied over a period of more than sixty years and can be explained by several physiological mechanisms. Although much is still to be learned about the action of acupuncture and the human body in general, the neural pathways from acupuncture point stimulation to the spinal cord to the pain centers in the brain have been well mapped out [8],[9]. (See figure 1)

Acupuncture has also been shown to activate a number of endogenous opioids and improve the brain's sensitivity to opioids [10]. A number of other biochemical substances involved in pain and pain reduction are found to be released or regulated by acupuncture stimulation, including ATP, adenosine, GABA, and substance P [11]. Research also shows that acupuncture reduces activity in brain areas associated with pain perception and increases activity in brain areas associated with improved self-regulation [12]. In this context, acupuncture is a safe and effective alternative with a long track record of successful use, without the side effects of pharmaceutical options for pain treatment.

Figure 1. The central nervous system

TREATMENT OF ONCOLOGIC PAIN
Painkillers are the common treatment for pain relief, the main types of which are non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, and opioids. These medications are used separately or together, depending on the severity of the pain [13]. The most widely used guidelines for physicians on how to provide the best pain management to patients have been developed by the World Health Organization (WHO). These guidelines include the three-step ladder for the treatment of oncologic pain. (See figure 2)

Figure 2. The WHO ladder for the treatment of oncological pain.

OPIOIDS
For moderate to severe oncological pain, opioids are the main choice. Despite very extensive use and recommendations from international guidelines, there remains a lack of high-quality studies to support this use. According to systematic reviews on the effectiveness of opioids in non-oncological pain, there is a lack of literature of high-quality RCTs with long-term follow-up and a lack of well-conducted non-randomized studies. Much less research is known about the effectiveness of treatment with opioids in oncological patients with chronic pain [14].

A recent Cochrane review providing an overview of assessments for opioids for cancer pain highlights the lack of data and notes that the quantity and quality of evidence regarding the use of opioids for the treatment of cancer pain is disappointingly low. This review also indicates that most people will experience side effects when using opioids [15].

Regarding the use of opioids to treat oncological pain in children and adolescents, a 2017 review concluded that 'no conclusions can be drawn about the efficacy and adverse effects of using opioids for the treatment of oncological pain in children and adolescents'. As a result, there is no randomized controlled trial evidence to support or refute the use of opioids in the treatment of oncological pain in children and adolescents [16]. The only randomized study that ever evaluated the long-term effectiveness of opioids for pain relief found that those who used opioids actually had more pain after twelve months compared to those treated with non-opioids for pain relief [17].

Wiffen et al, Cochrane Database of Systematic Reviews, 2017 [18]

NSAIDs AND PARACETAMOL
For mild to moderate pain, NSAIDs and paracetamol (also known as non-opioids) are the first choice. Concerns about the side effects and safety of taking such painkillers have increased in recent years. A 2017 review on the safety of NSAIDs in 440,000 patients shows an increased risk of heart attack with NSAID use at any dose, even if it is only for one week [19]. NSAIDs have also been shown to increase the risk of gastrointestinal bleeding (a serious and potentially fatal complication) and even acute kidney injury [20], [21]. A systematic literature review from 2016 on safety found an increased risk of cardiovascular complications, gastrointestinal bleeding, uremia, and death from the use of paracetamol [22].

Recent evidence on the analgesic effect of non-opioids is generally scarce. A 2017 Cochrane systematic review on the use of paracetamol for oncologic pain in adults and children concludes that there is no high-quality evidence supporting or refuting the use of paracetamol, alone or in combination with opioids, in the first two steps of the WHO cancer pain ladder [23].

A systematic review from 2017 of NSAIDs for oncologic pain in adults, including side effects associated with their use, concludes that there is no high-quality evidence demonstrating that NSAIDs are beneficial in treating people with oncologic pain. In some adults with moderate or severe oncologic pain, NSAIDs provide pain relief within one or two weeks, but the clinical evidence for this is of very low quality [24].

A similar review on the treatment of oncological pain in children and adolescents (<17 years) concludes that due to lack of information (overall quality is therefore very low) there is no evidence to support the use of NSAIDs for the treatment of cancer pain in children and adolescents [25].

OTHER OPTIONS FOR TREATING ONCOLOGIC PAIN
Other treatments for oncologic pain include antidepressants, antihistamines, anti-anxiety medications, stimulants and amphetamines, anticonvulsants, steroids, and complementary and alternative therapies [26]. These treatments are largely subject to a lack of clinical data. Compared to medication, which is associated with side effects and lacks sufficient clinical evidence of effectiveness to support its use, acupuncture offers a safe, cost-effective, and evidence-based treatment for oncologic pain.

Derry et al 2017, Cochrane Systematic Review. [27]

References:

1. Chiu HY, Hsieh YJ, Tsai PS. Systematic review and meta-analysis of acupuncture to reduce cancer-related pain. Eur J Cancer Care.
February 2016:n/a–n/a. doi:10.1111/ecc.12457.[←]

2. Paley, C.A., Johnson, M.I., Tashani, O.A. and Bagnall, A.M., 2011.
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4. Chiu HY, Hsieh YJ, Tsai PS. Systematic review and meta-analysis of acupuncture to reduce cancer-related pain. Eur J Cancer Care.
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5. Feeney C, Bruns E, LeCompte G, Forati A, Chen T, Matecki A. Acupuncture for Pain and Nausea in the Intensive Care Unit: A Feasibility Study in a Public Safety Net Hospital. The Journal of Alternative and Complementary Medicine.
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13. American Cancer Society. Non-opioids and Other Drugs Used to Treat Cancer Pain.
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15. Wiffen PJ, Wee B, Derry S, Bell RF, Moore RA. Opioids for cancer pain – an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;7:CD012592. doi:10.1002/14651858.CD012592.pub2.[←]

16. Wiffen PJ, Cooper TE, Anderson A-K, et al. Opioids for cancer-related pain in children and adolescents. Cochrane Database Syst Rev. 2017;7:CD012564. doi:10.1002/14651858.CD012564.pub2.[←]

17. Krebs EE, Gravely A, Nugent S, et al. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain. JAMA. 2018;319(9):872–11. doi:10.1001/jama.2018.0899.[←]

18. Wiffen PJ, Wee B, Derry S, Bell RF, Moore RA. Opioids for cancer pain-an overview of Cochrane reviews. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd. 2017 [←]

19. Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ.
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20. Lanas A, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13(5):906–12.e2. doi:10.1016/j.cgh.2014.11.007.[←]

21. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26(4):285-291. doi:10.1016/j.ejim.2015.03.008.[←]

22. Roberts E, Delgado Nunes V, Buckner S, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2016;75(3):552-559. doi:10.1136/annrheumdis-2014-206914.[←]

23. Wiffen PJ, Derry S, Moore RA, et al. Oral paracetamol (acetaminophen) for cancer pain. Cochrane Database Syst Rev. 2017;7:CD012637. doi:10.1002/14651858.CD012637.pub2.[←]

24. Derry S, Wiffen PJ, Rev RMDS, 2017. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. Wiley Online Library. doi:10.1002/14651858.CD012638.[←]

25. Cooper TE, Heathcote LC, Anderson B, Grégoire M-C, Ljungman G, Eccleston C. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for Cancer-Related Pain in Children and Adolescents. Vol 25. (Cooper TE, ed.). Chichester, UK: John Wiley & Sons, Ltd; 2017:259–15. doi:10.1002/14651858.CD012563.[←]

26. American Cancer Society. Non-opioids and Other Drugs Used to Treat Cancer Pain.
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27. Derry, S., Wiffen, P. J., Rev, R. M. D. S., 2017. (n.d.). Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. Wiley Online Library.
http://doi.org/10.1002/14651858.CD012638 [←]

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