Editor’s note: One in a series of articles on managing cancer-related symptoms from the Oncology Nursing Society. The literature search for the ONS Putting Evidence Into Practice: Pain, upon which this article is based, was completed in May 2008. ONS is currently updating the synthesis of findings for interventions in pain.

Nociceptive pain, caused by an injury to body tissue, or neuropathic pain, caused by damage to the peripheral or central nervous system, occurs in an estimated 50% of patients with cancer and 80%-90% of patients with advanced disease (Aiello-Laws, Ameringer, & Eaton, 2009; Miaskowski, 2005). The majority of pain originates from the tumor site, but it may result from the cancer treatment itself. However, there also is the possibility that the pain is unrelated to either the tumor or the treatment (Paice, 2004).

Nociceptive pain usually is characterized as aching, a sharp feeling, or throbbing (Pfizer Inc., 2007). Neuropathic pain commonly involves an unpleasant or abnormal sense of touch, an abnormal increase in sensitivity, or a shooting or lancinating sensation from nerve injury or compression (Ross et al., 2005). Because of these troubling symptoms and the uncertainty of where the pain is originating from, it is imperative that oncology nurses screen patients for risk and contributing factors as well as physical, psychosocial, and neurologic symptoms (Aiello-Laws et al., 2009) (See Pain assessment checklist.). In addition to obtaining a through history and performing a physical examination, nurses should consider using a clinical assessment tool such as the Brief Pain Inventory-short form (Cleeland, 1991), the Numeric Pain Intensity Scale, or the Visual Analog Scale (D’Arcy, 2007).

Putting evidence into practice

To promote nursing practice that is based on evidence, the Oncology Nursing Society (ONS) launched the Putting Evidence Into Practice (PEP) program in 2005. ONS PEP teams consisting of advanced practice nurses, staff nurses, and a nurse scientist were charged with reviewing the literature to determine what treatments and interventions are proven to alleviate many cancer-related problems that are sensitive to nursing interventions. Each team classified interventions under the following categories: recommended for practice, likely to be effective, benefits balanced with harms, effectiveness not established, effectiveness unlikely, and not recommended for practice.

Recommended for practice

The recommended for practice category lists interventions for which effectiveness has been demonstrated by strong evidence from rigorously conducted studies, meta-analyses, or systemic reviews (Aiello-Laws et al., 2009). For nociceptive pain, five interventions are listed as recommended for practice.

Acetaminophen is an effective analgesic for mild pain. Acetaminophen also can be used in conjunction with opioids in order to reduce or maintain the opioid (dose-sparing effect) (American Pain Society [APS], 2005; National Comprehensive Cancer Network [NCCN], 2008). In general, acetaminophen is well-tolerated up to 4 g per day (or 3 g per day in older adults) (NCCN, 2008). However, chronic daily usage could increase hepatic toxicity, and doses should not exceed 2.5 g per day in patients who drink 2 ounces of alcohol or more daily. Nurses should caution patients about potential renal and hepatic damage from acute overdose (Aiello-Laws et al., 2009).

Nonsteroidal anti-inflammatory drugs (NSAIDs)

are effective for many cancer-related pains. NSAIDs can be used to manage acute and persistent pain (APS, 2005); however, they do have the potential to cause decreased platelet aggregation, gastrointestinal discomfort, and renal and cardiac toxicity. In addition, all prescription NSAIDs can increase the risk for a heart attack or stroke as well as bleeding and ulcers (McNichol, Strassels, Goudas, Lau, & Carr, 2005), so nurses must be aware of these potentially fatal side effects.

Opioids can be used for moderate to severe acute and persistent pain (APS, 2005; NCCN, 2008; Nicholson, 2007). Opioids can bind directly to opioid receptors and there is no ceiling dose effect (APS, 2005). For persistent pain, healthcare professionals should administer a long-acting opioid. For patients experiencing breakthrough pain, an immediate-release opioid (on an as needed basis) should be provided (Currow, Plummer, Cooney, Gorman, & Glare, 2007; Mercandante et al., 2008; Wiffen & McQuay, 2007).

The most common side effects of opioids are constipation, sedation, and nausea and vomiting (APS, 2005; Komurcu et al., 2007; Pan et al., 2007). Other side effects that nurses should be aware of include respiratory depression, dry mouth, pruritus, and myoclonus (APS, 2005). Nurses should initiate a bowel regimen consisting of a softener and a laxative when a patient starts opioid therapy.

Corticosteroids are used to manage acute and persistent cancer pain. Corticosteroids may be an effective option, but nurses should be aware of potential side effects such as chronic weight gain (with long-term use), osteoporosis, Cushing syndrome, proximal myopathy, euphoria, increased appetite, and psychosis (Aiello-Laws et al., 2009). In addition, gastrointestinal bleeding may occur, particularly when a corticosteroid is coupled with an NSAID or anticoagulant. Finally, dosages should be tapered as rapid withdrawal can exacerbate pain and cause adrenal insufficiency (APS, 2005).

Local anesthetics, topical or injectable, are an effective way to reduce pain associated with lumbar puncture, bone marrow aspirate, and port access (APS, 2005).

For neuropathic pain, four interventions are listed as recommended for practice.
Regarding anticonvulstants, gabapentin is the most widely studied and best tolerated drug (APS, 2005; NCCN, 2008; Pergolizzi et al., 2006). Anticonvulsants are an effective way to treat trigeminal neuralgia, postherpetic neuralgia, glossopharyngeal neuralgia, and post-traumatic neuralgia (Aiello-Laws et al., 2009). However, not all anticonvulsants are recommended for practice—phenytoin has been found to be effective against neuropathic pain, but the many side effect and required close monitoring of serum drug levels are troubling (Aiello-Laws et al., 2009).

Antidepressants are an effective first-line treatment for neuropathic pain (Merck Manuals, n.d.), particularly pain from surgical trauma, postherpetic neuralgia, radiation therapy, chemotherapy, or malignant nerve infiltration (Aiello-Laws et al., 2009). Healthcare professional should start doses low and then slowly titrate up until a level of desired pain relief is reached (APS, 2005).

Serotonin-norepinephrine reuptake inhibitors (SNRIs), particularly duloxetine, had demonstrated significant pain relief in three randomly controlled trials (Merck Manuals, n.d.). However, venlafaxine demonstrated inconsistent results in pain related to postmastectomy, but was effective for other painful polyneuropathies (Merck Manuals, n.d.).

Finally, tramadol, a weak mu-opioid agonist, has been effectively used as a second-line medication when stronger opioids are not effective. Nurses should be aware of side effects, which are more pronounced when the drug is started at full dose: dizziness, nausea, constipation, and somnolence. Doses should be gradually titrated over weeks or months (Aiello Laws et al., 2009).

Likely to be effective

The likely to be effective category lists interventions for which effectiveness has been demonstrated by supportive evidence from a single rigorously conducted controlled trial, consistent supportive evidence from well-designed controlled trials using small samples, or guidelines developed from evidence and supported by expert opinion (Aiello-Laws et al., 2009). For this category, two items have been listed for nociceptive pain (none for neuropathic pain).

Bisphosphonates inhibit osteoclastic bone resorption and reduce pain in skeletal complications (e.g., pathological fractures in patients suffering from breast cancer or multiple myeloma). Bisphosphonates may be used when analgesics or radiotherapy are inadequate (Auret et al., 2006; Glare, Walsh, & Sheehan, 2006); however, nurses should be aware that bisphosphonates may cause osteoradionecrosis of the jaw (Challapalli, Tremont-Lukats, McNicol, Lau, & Carr, 2005).

Radionuclides or radioisotopes are useful for diffuse metastatic bone pain (Baczyk et al., 2007). However, response can take two to three weeks in some cases; therefore, patients must continue analgesic therapy (APS, 2005). Side effects including leukocytopenia and thrombocytopenia can occur (Baczyk et al., 2007; Dworkin et al., 2007).

Benefits balanced with harms

This category lists interventions for which healthcare professionals and patients should weigh the beneficial nature of the treatment with the harmful effects. For nociceptive pain, Aiello-Laws et al. (2009) listed spinal opioids and caffeine. However, long-term use of spinal opioids can cause problems with catheters (which can be costly) (Ross et al., 2005, and rebound pain and headache may occur when caffeine use is abruptly stopped (APS, 2005). For neuropathic pain, sympatholytic agents are listed (Aiello-Laws et al., 2009). In particular, epidural clonidine may be an effective way of relieving this type of pain; however, bradycardia and hypotension can occur (APS, 2005).

Effectiveness not established

Regarding interventions for which insufficient or conflicting data, as well as data of inadequate quality, currently exist, the following have been listed for nociceptive pain (no items are listed for neuropathic pain).

Ketamine—A small controlled trial reported effectiveness with nonmalignant neuropathic pain, but intolerable side effects occurred with IV administration (APS, 2005).

Antihistamines—These drugs can be used concurrently with analgesia as sleep aids and to reduce itching. As mild central nervous system depressants, antihistamines may increase analgesic effect (APS, 2005).

Dextroamphetamine—Combined with opioids in a postoperative stage, dextroamphetamine may produce an additive analgesia (APS, 2005).

Topical agents—While topical agents can “act locally” when applied directly to a painful area of the body, medications from compounding pharmacies should be used cautiously as drug formulation can result in either systemic activity or lack of penetration (APS, 2005).

Tetrodotoxin—This agent is a neurotoxin studied for the treatment of pain (administered either subcutaneously or intramuscularly) (Hagan et al., 2007, 2008). However, the few studies examining its use have reported inconsistent findings.

Skeletal muscle relaxants—Mixed evidence exists for the use of these agents for muscle injury. APS (2005) recommends their use for only a few days as needed.

Effectiveness unlikely/not recommended for practice

Aiello-Laws et al. (2009) list the following items as effectiveness unlikely for neuropathic pain (none listed for nociceptive pain): antidepressants, antiarrythmics, calcitonin, dextromethorphan, and capsaicin. Items listed as not recommended for practice include mixed agonists and antagonists, meperidine, propoxyphene, codeine, placebos, phenothiazine, carbamazepine, and using an intramuscular route.

Nurses are in a unique position to support patients suffering from pain by using evidence-based interventions. In addition to initiating treatments, nurses should assess the impact of pain on patients and their families, provide instruction and information about potential management options, and help patients maintain treatment adherence.

Sean Pieszak is a staff editor in the publications department at the Oncology Nursing Society in Pittsburgh, PA. More information about the ONS PEP classification for pain can be found at http://www.ons.org/Research/PEP/Pain.

Selected references

Aiello-Laws, L.B., Ameringer, S.W., & Eaton, L.H. (2009). Pain. In L.H. Eaton and J.M. Tipton (Eds.), Putting Evidence Into Practice: Improving oncology patient outcomes (pp. 215-234). Pittsburgh, PA: Oncology Nursing Society.

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Auret, K., Roger Goucke, C., Ilett, K.F., Page-Sharp, M., Boyd, F., & Oh, T.E. (2006).
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Baczyk, M., Czepczynski, R., Milecki, P., Pisarek, M., Oleska, R., & Sowinski, J. (2007). 89Sr versus 153m-EDTMP: Comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nuclear Medicine Communications, 28, 245-250.

Challapalli V., Tremont-Lukats, I.W., McNicol E.D., Lau J., & Carr D.B. (2005). Systemic
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Cleeland, C.S. (1991). Research in cancer pain. What we know and what we need to know. Cancer, 67(Suppl.), 823-827.

Currow, D.C., Plummer, J.L., Cooney, N.J., Gorman, D., & Glare, P.A. (2007). A randomized, double-blind, multi-site, crossover, placebo-controlled equivalence study of morning versus evening once-daily sustained-release morphine sulfate in people with pain from advanced cancer. Journal of Pain Symptom Management, 34, 17-23.

D’Arcy, Y. (2007). Pain management: Evidence-based tools and techniques for nursing professionals. Marblehead, MA: HCPro, Inc.

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Glare, P., Walsh, D., & Sheehan, D. (2006). The adverse effects of morphine: A
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Hagen, N.A., Fisher, K.M., Lapointe, B., du Souich, P., Chary, S., Moulin, D., Ngoc, A.H. (2007). An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. Journal of Pain and Symptom Management, 34, 171-182.

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Pan, H., Zhang, Z., Zhang, Y., Xu, N., Lu, L., & Dou, C. (2007). Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clinical Drug Investigation, 27, 259-267.

Pergolizzi, S., Iati, G., Santacaterina, A., Palazzolo, C., Di Pietro, A., & Garufi, G. (2006). Treatment planning in patients with bone metastases. Final results of a prospective study using pre-medication with fentanyl to improve irradiation reproducibility. Supportive and Palliative Cancer Care, 2, 71–75.

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