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11 Articles in Volume 13, Issue #6
Ask the Expert: Cash Patient on High-Dose Oxycodone With Negative Urine Screens
Cluster Headache: Providing Relief for a Debilitating Disorder
Editor's Memo: Keeping the Trust in Difficult Times
Gout: New Guidelines for Managing An Ancient Disease
History of Pain: A Brief Overview of the 17th and 18th Centuries
Letters to The Editor: Guidelines for Opioid Prescribing, Drug Legislation
Long-term Opioids, Sickle Cell Disease, and Pain Patches
Lumbar Spinal Stenosis: A Review of the Treatment Options and Modalities
Malabsorption of Opioid Medications
Non-Opioid Pharmaceutical Treatment of Cancer Pain
Treatment of Postherpetic Neuralgia With Low Level Laser Therapy

Non-Opioid Pharmaceutical Treatment of Cancer Pain

Approximately 33% of cancer patients experience long-term pain. Many cancer patients are living longer, shifting pain management from a focus on acute pain to chronic pain. Part 3 of this four-part series on cancer pain will serve as a practical guide for commonly used adjuvant therapies and contain tips for using the most effective agents.

Pharmacotherapy continues to be the cornerstone of cancer pain management (Part 1 and Part 2). The art of cancer pain management is choosing the specific medications that have dual usage or indications for maximizing the beneficial effects of rational polypharmacy without resulting in adverse drug interactions, side effects, and organ toxicity.1 Effective cancer pain treatment improves outcomes with decreased morbidity, improved function, reduced anxiety and depression, and a higher quality of life.2,3 One also must be mindful of polypharmacy, drug–drug interactions, and systemic side effects—particularly in the elderly—when combining these adjunctive medications.4 All medications prescribed should be used with caution, particularly if they are given “off label,” and with informed consent, the risks and benefits assessment must be discussed with the patient and caregiver prior to treatment.

The non-opioid analgesics include a diverse group of medication classes including acetaminophen (APAP), non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, topical analgesics, hypnotics, muscle relaxants, cannabinoids, N-Methyl-D-aspartate (NMDA) receptor antagonists, and others. In general, nociceptive pain can be responsive to NSAIDs, corticosteroids, and opioids; and neuropathic pain can be responsive to topical anesthetics, antidepressants, anticonvulsants, and opioids (at higher doses). Most of the adjunctive medications discussed in this paper are based on non-malignant pain, clinical experience, and expert opinion, along with cancer pain guidelines (which generally emphasize opioid management).5-7

Acetaminophen

APAP is commonly used as a first-line analgesic and antipyretic, and is available over the counter. For acute pain, the maximum APAP dose is 4,000 mg per day in healthy adults (3,000 mg daily in elderly adults),8 although it is currently limited to 2,600 mg per day for chronic usage due to an increased risk of renal insufficiency as the result of its effects on prostaglandins.9 One should reduce the maximum dose by 50% to 75% in patients with liver disease including metastasis or hepatitis, or in those with a history of alcohol abuse.10 Recent reports also suggest an increased risk of hearing loss,11,12 and renal carcinoma13,14 with chronic usage. APAP is often coupled with schedule III opioids for a synergistic analgesic effect. In 2011, the FDA urged manufacturers of these products to limit the amount of acetaminophen to 325 mg per tablet (ie, Vicodin, Lortab, Norco, Primlev [300 mg APAP], and Percocet).15 In addition, there are newer formulations of APAP, including intravenous (IV) APAP (Ofirmev, approved in 2010), an elixir, and a rectal suppository. APAP should be preferred over NSAIDs when used in combination with World Health Organization (WHO) step III opioids because of a more favorable side-effect profile, but its efficacy is not well documented.5

NSAIDs

NSAIDs may be added to WHO step III opioids to improve analgesia or reduce the opioid dose required to achieve analgesia. Generally, the analgesic and antipyretic effects of NSAIDs can be obtained at lower doses, and the anti-inflammatory effects at higher doses. Studies show little difference between individual drug effectiveness.10

NSAIDs are particularly effective at treating bone metastasis and pathologic fractures,4,5 although they may have an inhibitory effect on boney healing. IV formulations of ibuprofen (Caldolor) and ketorolac (Toradol) are available, as well as an intranasal formulation of ketorolac (Sprix). With IV ketorolac, studies have found that there is better overall analgesia and a slower opioid escalation in cancer patients in comparison to patients treated with opioids alone.16 Any pain generator(s), including visceral pain, seemed to be equally sensitive to NSAIDs.

The continued use of NSAIDs, however, should be restricted because of the risks of serious adverse effects, in particular in elderly patients and those with gastrointestinal (GI), renal, hepatic, or cardiac disease. It is recommended that patients at greater risk for GI toxicity take NSAIDs with a proton pump inhibitor or histamine 2 blockers. Cyclo-oxygenase 2 selective medications (ie, celecoxib, Celebrex) have a similar analgesic efficacy, but are safer in older patients with all GI comorbidities, lower GI bleeding risks, or those on anticoagulants or anti-platelet regimens.17 They can be used preoperatively and postoperatively since they do not affect platelet aggregation, and have been used for pre-emptive analgesia. Because NSAIDs are metabolized in the liver, they may be subject to drug–drug interactions in patients with cytochrome P 450 (CYP450) defects.

Salicylated NSAIDs have fewer anti-platelet effects, comparable to celecoxib (which is contraindicated with a sulfa allergy). Based on cardiovascular morbidity meta-analysis, naproxen has shown a lower risk, with ibuprofen and celecoxib close to parity, and there is a higher relative risk for meloxicam and oral diclofenac. Diclofenac also has higher risk of liver toxicity, sulindac has less renal metabolism, meloxicam (at lower doses) has a favorable upper GI side-effect profile, and nabumetone is a pre-drug, which requires hepatic metabolism, but may reduce first pass upper GI toxicity. If a patient is on aspirin (ASA) prophylaxis, it is better to take ASA first to allow platelet binding, and then wait 1 hour to take the analgesic NSAID.

Other adverse effects with chronic NSAID use include renal carcinoma13,14 and atrial fibrillation.18 Topical NSAIDs, particularly diclofenac (patches, solutions, or gels), have been used for localized pain, and all topical agents have approximately 5% to 10% systemic absorption. There are now studies suggesting that chronic ASA use, and possibly other NSAIDs, may reduce the risk of GI (especially colon, esophagus, liver, and pancreas), skin, breast, ovarian, bladder, and prostate malignancies.19 There are antioxidant, anti-inflammatory supplements, or medical foods—including flavocoxib (Limbrel), which is FDA approved for the management of osteoarthritis—which may also be considered in patients in whom NSAIDs would otherwise be contraindicated.

Corticosteroids

Corticosteroids may reduce edema and inflammation, and stabilize nerve membranes. Corticosteroids possess analgesic properties for a variety of cancer pain syndromes, including bone pain and neuropathic pain from infiltration or compression of neural structures. They also alleviate nausea and increase mood and appetite, and may be used for symptoms associated with bowel obstruction.4 Acute use may result in peptic ulcers, psychosis, fluid retention, immunosuppression, and leukocytosis. Chronic use can increase risk of hyperglycemia, weight gain, osteoporosis, avascular necrosis, cataracts, myalgias and myopathy, and delayed wound healing. Therefore, corticosteroids that are required for more than 2 weeks duration should be used with caution, and should be tapered to reduce the risk of adrenal suppression.

Antidepressants

Antidepressants have been specifically studied in cancer-related pain only in post-mastectomy syndrome (tricyclic antidepressants [TCAs] were effective) and in chemotherapy (CT)-induced neuropathic pain (TCAs were not effective).4 TCAs have efficacy in the treatment of neuropathic pain and associated comorbid depression. The doses effective for neuropathic pain are usually lower than those used for depression. Amitriptyline, imipramine, nortriptyline (which is also an active metabolite of amitriptyline), and desipramine have analgesic effects in cancer patients, especially for concurrent neuropathic pain syndrome,4 but must be used cautiously in the elderly due to side effects of sedation, constipation, urinary retention, orthostasis, and cardiac arrhythmias.

Duloxetine (Cymbalta), which is usually dosed at 60 mg per day, has recently been shown to be effective in treating CT-induced peripheral neuropathy pain, with improved quality of life.20 It should be used cautiously in patients with liver or renal disease, and closed-angle glaucoma. Other medications with similar mechanisms of action have been used to treat neuropathic pain, including milnacipran (Savella)—which is approved for fibromyalgia and can cause GI upset—venlafaxine (Effexor), or desvenlafaxine (Pristiq), which may treat hot flashes and may elevate blood pressure.21 Low-dose paroxetine has just been FDA approved for hot flashes. The selective serotonin reuptake inhibitors are not generally considered effective analgesics.4 Mirtazapine (Remeron), which has serotonergic and antihistamine effects, may be effective for improving multiple symptoms including nausea, anxiety, insomnia, and appetite in addition to depression to improve quality of life in patients with advanced cancer.22 Bupropion (Wellbutrin, Zyban, Aplenzin), which selectively blocks reuptake of norepinephrine and dopamine receptors, is an activating antidepressant, and can improve sexual function and may be analgesic in neuropathic pain.4 It must be used cautiously in patients with a seizure disorder or anorexia.

The dose titration for all antidepressants is usually slow, though clinical effects may be observed within 2 weeks at lower doses, and therapeutic effects achieved within 4 weeks. Precautions for all antidepressants include suicidal ideation in younger adults, risk of serotonin or neuroleptic syndrome, lowering seizure threshold, and sexual dysfunction. Many antidepressants affect the CYP450 system (except desvenlafaxine, sertraline, and escitalopram), which can interact with antimicrobials, as well as prolongation QTc by electrocardiogram (especially paroxetine and citalopram), and may increase opioid drug metabolism (through CYP450-2D6 effects), thereby reducing therapeutic opioid levels with duloxetine, venlafaxine, amitriptyline, fluoxetine, and paroxetine.

Anticonvulsants

All anticonvulsants can be used to treat neuropathic pain. Gabapentin (Neurontin, Gralise, Horizant), usually at doses 1,800 to 3,600 mg per day, and pregabalin (Lyrica), usually at 150 to 600 mg per day, have shown improvement of symptoms in cancer-related neuropathic pain.4 These two anticonvulsants are currently being studied in the management of bone cancer pain. Gabapentin and pregabalin also have anxiolytic effects.10 These medications can be used to effectively treat postherpetic neuralgia (PHN), which can be associated with immunosuppression for cancer therapies, as well as treating restless leg syndrome related to CT-induced peripheral polyneuropathy. One trial reported that the addition of levetiracetam (Keppra) to gabapentin provided synergistic relief, and another trial suggested that adding lamotrigine (Lomictal) to phenytoin (Dilantin) or carbamazepine (Tegretol) was beneficial to cancer pain patients.4

Studies have shown that the combination amitriptyline (Elavil) and gabapentin was effectively used in patients with neuropathic cancer pain that were only partially responsive to opioid analgesia.23 Other anticonvulsants—including phenytoin, carbamazepine, oxcarbazepine (Trileptal), lamotrigine, levetiracetam, and valproate products—are thought to play a role in the suppression of ectopic discharges via inhibition of sodium channels. Topiramate (Topamax) and zonisamide (Zonegran) have been used clinically for headache prophylaxis and appetite suppression, but must be used cautiously in patients with narrow angle glaucoma and renal lithiasis (due to alterations in chlorine metabolism).

Potential side effects of anticonvulsants include angioedema, drowsiness, dizziness, blood dyscrasias, weight gain, and suicidal ideation. The dose titration is generally slow, and clinical effects may be achieved within 2 to 4 weeks. All anticonvulsants carry a precaution with pregnancy, and should not be abruptly discontinued when ineffective.

Agents for Osteoporosis and Pathologic Fractures

IV bisphosphonates are important agents for the management of pain from malignancies, metastatic bone disease, and hypercalcemia due to cancer, as well as osteoporosis. These agents tend to delay time to painful skeletal events and have analgesic properties for bone pain.4

Pamidronate (Aredia) has been shown effective in breast cancer and multiple myeloma with reduced occurrences of pathological fractures, the need for bone radiation or surgery, spinal cord compression, and hypercalcemia. The recommended dose is 60 to 90 mg IV (infused over 2-4 hours) every 3 to 4 weeks. Adverse effects, including hypocalcemia and a flu-like syndrome, are dose related and typically transitory.

Zoledronic acid (Reclast, Zometa) is approximately 2 to 3 times more potent than pamidronate, and is used to treat both osteoblastic and osteolytic lesions of breast cancer, prostate cancer, multiple myeloma, and solid tumors—including lung cancer. It is slowly infused over 15 minutes to a dose of 4 mg, given every 3 weeks. Side effects include hypocalcemia, fever, GI disturbances, anemia, and rarely, nephrotoxicity, jaw osteonecrosis, and increased risk of mid-femoral fractures.

Calcitonin may be used for pain from bone metastasis or osteoporosis. Calcitonin-salmon (Calcimar) may also be used subcutaneously for compression fracture, where it has some intrinsic analgesic effects. For intranasal calcitonin (Miacalcin), the initial dose is 200 IU spray in one nostril daily, alternating nostrils every day. Periodic monitoring of calcium and phosphorus is prudent during treatment. Apart from infrequent hypersensitivity reactions associated with subcutaneous injections, the main side effect is nausea.4

Teriparatide (Forteo) is a recombinant form of parathyroid hormone, used in the treatment of severe osteoporosis (particularly if there are fractures) and following prolonged corticosteroid therapy or with hypogonadism. It is the only available agent that stimulates new bone formation. It is given 20 μg subcutaneously daily for 2 years, due to possible risk of osteosarcoma. It is contraindicated in patients who have undergone radiation therapy to the skeleton, Paget’s disease, hypercalcemia, or hyperparathyroidism.24

Denosumab (Prolia, Xgeva) is a human monoclonal antibody that inhibits RANK ligand, a protein in the boney remodeling cascade that acts as the primary signal for bone removal. It is approved for the treatment of osteoporosis, treatment-induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma, and giant cell tumor of bone. It is administered subcutaneously in postmenopausal women every 6 months, and may cause immunosuppression.25

Systemic radiopharmaceuticals such as strontium-89 and samarium may also be used for the treatment of pain from bone metastasis if RT is ineffective or contraindicated. Radionuclides absorbed at areas of high bone turnover have been assessed as potential therapies for metastatic bone pain. Strontium-89 and samarium-153 are commercially available and found to be effective as monotherapy or as an adjunct to conventional RT. Given the potential for myelosuppression associated with their use, these drugs usually are considered when pain is refractory to other modalities.4

Supplements

Calcium can be used for fracture healing (if there is no hypercalcemia or renal lithiasis), but recent studies have reported a cardiac risk with this supplement.26 Magnesium may be required to improve absorption of calcium for osteoporosis, treat muscle pain, and is helpful as a laxative. Vitamin D supplementation may be helpful for bone healing, osteoporosis, weakness, fatigue, prevention of cancer, depression, cardiac disease, and falls.

NMDA Receptor Antagonists

Ketamine (Ketalar) is an NMDA receptor antagonist that has been used parenterally, topically, or orally (poor bioavailability) to alleviate opioid-induced hyperalgesia (OIH) and tolerance. Ketamine, administered by IV infusion or orally, is effective in relieving cancer pain, neuropathic pain, and reducing opioid requirements.4 It is also widely being investigated as an antidepressant. Clinicians should use this medication with caution due to hallucinatory effects with higher doses of ketamine and the potential for abuse.

Other NMDA antagonists include dextromethorphan (used as a cough suppressant), amantadine (used to treat influenza), memantine (used to treat dementia), and methadone (d-isomer).3 Amadatine, an antiviral agent, has been used for treatment of asthenia and fatigue.

α2 Adrenergic Agonists

Clonidine (Catapres) and tizanidine (Zanaflex) are preganglionic α2 adrenergic agonists and may be considered nonspecific adjuvant analgesics. Clonidine may be administered orally, via a weekly patch (Catapres TTS) for systemic use, or topically for local use. Intrathecal clonidine has been shown to reduce pain (especially neuropathic pain) in patients with severe intractable cancer pain partly responding to opioids.4 It can also be used for opioid or tobacco cessation, complex regional pain syndrome, anxiety, attention deficit disorder (in children), and labile hypertension due to uncontrolled pain. The supporting data are limited and the side effects include somnolence and hypotension.

Other antihypertensives may be used for sympathetic induced pain (α or calcium channel blockers) or post-traumatic stress disorder (α blockers). Tizanidine is approved as an antispasticity agent, with additional analgesic effects on myalgias for the treatment of myofascial pain syndromes and muscle tension headaches. Hypotension is less common, but it may cause liver function abnormalities and prolonged QTc (due to CYP450-3A4 effects). Dexmedetomidine (Precedex), available only in IV form, has sedative, analgesic, sympatholytic, and anxiolytic effects, and has recently been used to minimize opioid requirements in the intensive care unit and for OIH.27

Muscle Relaxants

Muscle relaxants may relieve musculoskeletal pain or spasm, based on a central mechanism of action, without directly relaxing striated muscle (except dantrolene). The FDA-approved muscle relaxants (including carisoprodol, cyclobenzaprine, orphenadrine, metaxalone, and methocarbamol) have only been approved for short-term use (up to 21 days), and their long-term use efficacy is unknown. The most common adverse effect is sedation, and treatment should be initiated with relatively low initial doses.4 If a muscle spasm is present and is believed to be responsible for the pain, one may consider diazepam (or other benzodiazepines), or baclofen. Baclofen is a γ-aminobutyric acid (GABA)-B receptor agonist, and has established efficacy in treating trigeminal neuralgia. It is often considered for a trial in any type of neuropathic pain. The effective dose range is very wide (20 mg/day to 120mg/day), and has been used intrathecally. The side effects may include asthenia, fatigue, and weakness. There is a possibility of a serious withdrawal syndrome including seizures on abrupt discontinuation. It is also used in treatment of spasticity and central pain secondary to spinal cord lesions. Spasticity from upper motor neuron disease may also be treated with dantrolene sodium.

Hypnotics

Hypnotics can be useful to improve sleep, which in turn can help patients cope with pain, and reduce the need for nighttime analgesics. These agents include selective or non-selective GABA agonists, ramelteon (Rozerem, a melatonin agonist), muscle relaxants, antihistamines, antidepressants, and sedating psychotropics.

Regarding benzodiazepines, evidence of analgesic effects is limited.4 Clonazepam, which is also considered an anticonvulsant, is an intrinsic long-acting benzodiazepine, and has been anecdotally used in refractory neuropathic pain.10 The side effects include sedation, changes in mentation, synergistic depressant effects with other central nervous system drugs, dependency, and withdrawal seizures.

Antihistamines

These medications are also used to treat patients for cancer-related symptoms or complications of cancer treatment, such as allergic reactions, dizziness, vertigo, nausea and vomiting, confusion and delirium, and constipation. Reportedly, hydroxyzine has a better effect in treating opioid-induced pruritus, and can be combined with opioids to give a synergistic effect.3 Non-sedating formulations have less anticholinergic binding.

Neuroleptics

Olanzapine (Zyprexa) has been reported to decrease pain intensity and opioid consumption, and improve cognitive function and anxiety in cancer patients.28 However, there is limited evidence that neuroleptic drugs have analgesic properties, though they’ve been used as antiemetics and appetite stimulants, and to treat gastroparesis and headaches.4 Given their potential for side effects and risks, neuroleptics are not clinically used as adjuvant analgesics unless the primary indication of delirium or agitation is present.4 They have been approved to treat mood disorders and should be used cautiously in the elderly due to cardiovascular morbidity and adverse effects on glucose metabolism. Ondansetron (Zofran) is a serotonin 5-HT3 receptor antagonist used as an antiemetic following CT, and has fewer sedating effects than neuroleptics.

Adjuvant Analgesics Used For Pain Caused by Bowel Obstruction

Regimens for constipation should be routinely used in most cancer patients on analgesic therapy, particularly if they are sedentary and have poor feedings. Octreotide and anticholinergic medications can be used in severe cases, particularly with paralytic ileus and malignant bowel obstruction for which opioids are generally contraindicated.4,29 Recent reports have implicated the chronic use of all anticholinergics in contributing to impaired cognition within 60 days.30

Local Anesthetics

Local anesthetics have analgesic properties in neuropathic pain related to the blockade of the sodium channel. There are few studies to support their use in cancer pain, but they are widely used in the treatment of musculoskeletal pain. Topical analgesics (including lidocaine 5% patch) have been used as a treatment for PHN, and clinical experience supports their use for other neuropathic pain conditions.

Most topical agents have fewer than 10% systemic absorption. A local anesthetic patch is usually applied 12 hours per day, up to 3 patches, though there are few studies that have shown adverse events with continuous exposure to topical local anesthetics. The most frequently reported adverse event is mild to moderate skin redness, rash, or irritation at the patch application site.10 These agents can be used in conjunction with trigger point injections or nerve blocks and may be used for pre-emptive analgesia. Brief IV infusions at low dose with telemetry monitoring can be administered, or use in intrathecal pumps may be considered if a trial of anticonvulsants or antidepressants has failed.4 Common adverse effects are paresthesias, abnormal taste, tinnitus, blurred vision, drowsiness, but toxic doses may cause seizures and cardiac arrest.

Mexiletine is an oral antiarrhythmic, which is structured similarly to lidocaine, has been used to treat patients with neuropathic pain from numerous etiologies, and is the preferred oral local anesthetic. Unfortunately, mexiletine has a high rate of adverse effects and discontinuation due to toxicity occurring in almost one-half of patients in one study.4

Cannabinoids

Marijuana includes more than 70 chemical compounds including cannabinoids. Formulations include oral (nabilone and dronabinol)—which have a longer duration of analgesic effect—a recently FDA-approved nasal spray (nabiximols), and a sublingual spray in development. They can provide analgesia without respiratory depression31 for an opioid sparing effect,32 have anticonvulsant properties for neuropathic pain,33 and have anti-inflammatory effects for muscle pain or arthralgias by their peripheral effects. Several states have approved dispensaries for selected patients, though marijuana is still considered a schedule I substance by the Drug Enforcement Administration. Cannabinoids have the potential for abuse and dependency as well as weight gain and lower libido.

Capsaicinoids

In cancer patients, capsaicin cream has been shown to be effective in reducing neuropathic postsurgical pain including post-mastectomy pain.4 There are two commercially available concentrations (Zostrix, 0.025% and Zostrix HP, 0.075%), to be applied three to four times daily, as well as a patch (Qutenza, 7%) applied every 3 months for PHN. A trial of several weeks is needed to adequately judge effects. A major side effect is localized irritation, which causes a burning sensation, and limits its use.

Psychostimulants

There is evidence that psychostimulant drugs dextroamphetamine (Adderal, Dexadrine, Vyvanse), methylphenidate (Ritalin), and caffeine have analgesic effects. In cancer patients, methylphenidate can reduce opioid-induced somnolence, improve cognition, treat depression, and alleviate fatigue.4 Treatment typically begins with 2.5 to 5 mg in the morning and again at midday, if necessary, to keep the patient alert during the day and not interfere with sleep at night. Doses are increased gradually until efficacy is established. These are schedule II medications with a risk for dependency, abuse, and withdrawal symptoms, and have cardiovascular toxicity.4 Modafinil (Provigil) and its racemic active isomer, armodafinil (Nuvigil), can be used for opioid-induced sedation,34 narcolepsy, and fatigue (particularly with sleep apnea) and may have adjunctive analgesic effects.35 Use these medications with caution in patients with severe renal disease. They may also cause Stevens-Johnson syndrome.36

Hormonal Therapy

For breast cancer pain, hormonal therapy (tamoxifen, raloxifene) can reduce the risk of osteoporosis and subsequent fractures, and improve cognition.4 Testosterone replacement or anabolic androgens (usually given in topical formulations, and occasionally intramuscularly, with monitoring of liver enzymes) may be required in patients with opioid-induced hypogonadism for improvement of libido, fatigue, muscle mass, osteoporosis, cognition, and wound healing. Male hormones should not be used with prostate cancer, and testosterone levels should be monitored. Leuprolide injections have been used for treatment and reduction of pain in prostate and breast cancer due to its anti-androgenic properties.1

Dopaminergic Agents

Carbidopa and levodopa combination, ropinirole, and pramipexole may be used for neuropathic pain and restless leg syndrome,4 which can be associated with iron deficiency anemia, pregnancy, fibromyalgia, and peripheral neuropathy from diabetes or CT.4 The side effects include nausea, hallucinations, and an increased risk of gambling addiction.

Ziconotide

Ziconotide (Prialt), derived from the cone snail, is a non-habituating intrathecal analgesic agent used to treat severe and chronic pain. It is an N-type voltage-gated calcium channel blocker, which inhibits the release of glutamate, calcitonin gene-related peptide, and substance P in the brain and spinal cord. Its side effects include nausea, ataxia, and psychosis.37

Botulinum Toxin

Botulinum toxin intramuscular injections can be considered for refractory musculoskeletal pain related to muscle spasms including trismus or myokymia occurring after radiation therapy.38 It may also be used for spasticity, uninhibited detrusor contractions, anal fissures, hyperhidrosis, dystonias, and chronic vascular headaches, which may occur as co-morbidities from cancer. It is administered every 3 months, with side effects including an immediate flu-like syndrome, dysphagia or dysarthria (if injected in the neck), and temporary weakness of the injected muscle.

Conclusion

The use of adjuvant analgesics in cancer patients is still often guided solely by anecdotal experience or derived from data on nonmalignant pain. Future studies focused on the cancer population are needed to expand and improve the use of these drugs. Part 4 discusses evaluation and treatment of chemo- and radiation-induced pain.

Last updated on: October 28, 2014
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