November/December 2014

Pain Management Strategies
By Ashish R. Udeshi, MD
Today's Geriatric Medicine
Vol. 7 No. 6 P. 14

Providers must take steps to identify the type and source of patients' pain and provide the most appropriate form of treatment.

Unfortunately, pain is a complaint expressed by many patients, and with an aging population, the incidence of pain conditions in the elderly is highly prevalent. Specific pain conditions affecting the elderly include musculoskeletal conditions ranging from osteoarthritis to degenerative spinal disorders. Other pain conditions found in the geriatric population include neuropathic and cancer-mediated diseases, such as postherpetic neuralgia, diabetic neuropathy, peripheral vascular disease, and neoplasm-related pain.

Diagnosing and treating the underlying cause of pain in the elderly can pose significant challenges because of their increased risk of multiple medical conditions, polypharmacy, communication barriers, and cognitive decline. To provide the most appropriate form of treatment, it is pertinent to understand the different classifications of pain.

Two general types of pain include nociceptive and neuropathic pain. Nociceptive pain is typically well localized, constant, and often with an aching or throbbing quality. Some examples include sprains, bone fractures, burns, bumps, bruises, myofascial pain, and inflammation. Nociceptive pain is more responsive to treatments focused on inflammatory mediators and opioid receptors.1

Neuropathic pain involves injury to the peripheral or central nervous system and is classified by burning, electrical shocklike activity, and lancinating pain. Some examples include postherpetic neuralgia, diabetic neuropathy, phantom limb, and components of cancer pain. Neuropathic pain is more responsive to nerve mediated pain medications such as neuromodulators, antidepressants, and antiepileptics. Some conditions can result from a combination of nociceptive and neuropathic pain.1

This article will review case presentations on nociceptive and neuropathic pain conditions in the elderly and discuss the various treatment options, including opioid and nonopioid therapies.

Case Study No. 1
Jane, a 68-year-old retired secretary, arrives at her primary care physician's office complaining of chronic daily joint stiffness and pain with minimal exertion. Her physical exam is positive for pain in her knees, lower back, and hip joints when she rises from sitting, bending over, or straightening up. Radiographic imaging of her hips, knees, and back reveals irregular joint space narrowing and signs consistent with osteoarthritis.

What medication should Jane take first?
Jane is suffering from mild to moderate osteoarthritis and musculoskeletal pain; she would be an ideal candidate to begin over-the-counter acetaminophen for breakthrough with a referral to physical therapy. Acetaminophen is the recommended first-line therapy according to the American Geriatrics Society (AGS) expert panel recommendations in 2009.2 It is not associated with significant gastrointestinal bleeding, adverse renal effects, or cardiovascular toxicity.

Prior to initiating acetaminophen, it is important to evaluate hepatic function because of the increased risk of hepatoxicity. The latest guidelines and recommendations from the FDA regarding acetaminophen usage include limiting the total daily consumption to <3 g under patient use and <4 g under physician-instructed use.3 This past year FDA requirements have also changed for combination medications containing acetaminophen. The new recommendation limits the amount per combination pill to 325 mg of acetaminophen in order to decrease the potential risk of liver failure.4

Jane presents to your office a couple weeks later indicating that her pain continues. She notes that her friend is taking a nonsteroidal anti-inflammatory drug (NSAID) and she would like to know whether she should take it.

In the general adult population, NSAID therapy has a good safety profile and can be effective for chronic musculoskeletal conditions. However, when dealing with elderly patients, use particular caution, especially for individuals with low creatinine clearance, gastropathy, or cardiovascular disease.2

Gastrointestinal toxicity in older patients creates a serious concern. Additionally, patients coadministered with low-dose aspirin and NSAIDs are at a higher risk of gastrointestinal bleeding. There are selective COX-2 inhibitors (celecoxib) with fewer gastrointestinal side effects; however, prior COX-2 inhibitors (rofecoxib, valdecoxib) were withdrawn because of adverse cardiovascular events and should be used with caution.2 However, topical NSAID therapy that minimizes systemic effects could be effective for short-term use in musculoskeletal pain.5

Depending on Jane's other comorbidities, the initiation of NSAID therapy should focus on key issues of pain amelioration, cardiovascular risk, nephrotoxicity, drug interactions, and gastrointestinal toxicity.

Although Jane started on acetaminophen, a topical NSAID, and began physical therapy, she continues to have moderate pain in her joints and wants something to help with breakthrough pain when she plays tennis a couple times per week.
This leads to the discussion of whether Jane is a good candidate for opioid therapy for chronic noncancer mediated pain in the elderly. All providers who care for elderly patients must decide based on their own clinical experience and published evidence whether or not to prescribe opioids. The following questions recommended by the AGS guidelines may assist in the decision-making process.2

Initial Evaluation
1. What is conventional practice for this type of pain or patient?

2. Is there an alternative therapy that is likely to have an equivalent or better therapeutic index for pain control, function restoration, and an improvement in quality of life?

3. Does the patient have medical problems that may increase the risk of opioid-related adverse effects?

4. Is the patient likely to manage the opioid therapy responsibly (or is caregiver likely to responsibly comanage)?

Role of Consultant or Specialist
1. Am I able to treat this patient without help?

2. Do I need the help of a pain specialist or other consultant to comanage this patient?

3. Are there appropriate specialists and resources available to help me comanage this patient?

4. Are the patient's medical, behavioral, or social circumstances so complex as to warrant referral to a pain medicine specialist for treatment?

According to the AGS panel recommendations, if the decision is made to prescribe, this should begin with an opioid trial program that consists of clearly defined therapeutic goals. The opioid trial would focus on finding the effective dose, utilizing a "start low, go slow" technique, with frequent attempts to avoid side effects and titrate medications. Additionally, medication therapy should be combined with other modalities of nonpharmacological treatments geared to improve function and quality of life (eg, physical/aqua therapy program, weight loss, diet, etc).2

Jane is prescribed hydrocodone/acetaminophen 5/325mg one-half tab po bid prn for her breakthrough pain and inquires about the risks associated with opioids.

Opioid medication risk can occur in general adult patients as well as in elderly patients. However, because of the different pharmacodynamic and pharmacokinetic effects in elderly patients, more vigilance is required. In starting elderly patients on opioids, the general rule is to reduce the adult dose by 50%.6 Moreover, the patient's other comorbidities may also influence the choice, route, and frequency of medication used.

For instance, with individuals who have swallowing difficulties, subcutaneous, transdermal, or intravenous options should be explored. Patients with renal or hepatic failure require reduced doses or alternative agents. Additionally, elderly individuals have the potential for other drug-drug interactions that can result in decreased metabolism and delayed excretion. These can lead to elevation in toxic metabolites, which can pose severe life-threatening side effects such as respiratory depression, cognitive decline, somnolence, increased risk of falls, and overdose. Other risks with opioids include the potential for long-term abuse, misuse, diversion, tolerance, and constipation. As a result, frequent monitoring is required for patients on chronic opioid therapy to ensure proper use.7

Case Study No. 2
Jack, an 84-year-old male, complains of lower extremity pain that is deep, aching, and burning, causing difficulty sleeping at night. He was diagnosed with diabetes more than 20 years ago. On physical exam he has allodynia to light touch and hyperalgesia in his feet and legs. He currently takes metformin and is on insulin therapy. He also suffers from cardiovascular disease, chronic obstructive pulmonary disease, and vascular dementia.

What type of pain is Jack suffering from?
Based on his complaints of burning, aching pain, with allodynia and hyperalgesia, Jack is suffering from neuropathic mediated pain due to his long-standing diabetes. With the ever-increasing elderly population, more patients are suffering complications of long-standing disease. It is reported that up to 50% of patients with diabetes can suffer from neuropathy conditions, and those who have had diabetes for more than 25 years are at substantially higher risk.8

Are there any topical agents Jack could use?
When treating elderly patients with multiple systemic and oral medications, alternatives such as topical agents directed at the site of pain can limit drug-drug and drug-disease interactions.

There are currently two topical agents for peripheral painful diabetic neuropathy: lidocaine and capsaicin. Lidocaine 5% can be used as a patch or gel and must be applied directly at the site. As a result, lidocaine systemic toxicity in adults is not considered a serious risk, though skin irritation can occur.5 Capsaicin 0.075% concentration can also be applied to the skin to enhance sensitivity to noxious stimuli and after repeated applications, lead to persistent desensitization. Unfortunately, in 30% of patients, the side effects of severe burning and skin irritation lead to early termination of treatment.8 In elderly patients with cognitive decline, there is also serious risk that inadvertent exposure to other areas of the body (eg, mucous membranes or eyes) can occur if applied incorrectly.9

Presently, new formulations of compounded topical agents combining N-methyl-D-aspartate receptor antagonists, muscle relaxants, anti-inflammatories, and neuromodulators, are emerging. Although they are not currently FDA approved, they could be suitable options for the right patient.10

What nonopioid medications are available for Jack to take to help his pain?
There are nonopioid alternatives for the initial treatment of diabetic neuropathy that include antiepileptics and antidepressants.

First-line treatments include tricyclic antidepressants (TCAs) such as amitriptyline and nortriptyline. However, starting these medications in elderly patients with multiple comorbidities warrants caution. In those patients with cardiac history, TCAs pose serious risk and are contraindicated. TCAs also have anticholinergic properties that can lead to orthostasis, urinary retention, and a host of illnesses that could affect elderly patients. Thus, care should be utilized in prescribing TCAs in patients aged 60 or older.11 Other antidepressant alternatives to TCAs include serotonin–norepinephrine reuptake inhibitors (eg, venla faxine, duloxetine) and selective serotonin reuptake inhibitors (eg, citalopram, paroxetine). Again, these pose the risk of serious effects on cardiac and cognitive function in the elderly and should be reserved as final treatment options.11

When choosing antiepileptics, the most commonly prescribed medications include gabapentin and pregabalin. These medications can have severe side effects such as confusion, somnolence, and peripheral edema. However, compared with TCAs and antidepressants, the effects are significantly less, making gabapentin and pregabalin the first-line options in elderly patients. Pregabalin is one of the few FDA-approved medications for treatment of diabetic peripheral neuropathy. When initiating the medication, remember to start low and go slow (ie, Lyrica 50mg po qhs).9

Finally, older antiepileptics such as carbamazepine, phenytoin, and valproate, have been used to treat neuropathy since the 1960s.8 However, adverse effects include drowsiness, dizziness, constipation, nausea, ataxia, and hyponatremia. Therefore, they are not ideal choices for elderly patients with multiple comorbidities.

When would you start Jack on an opioid medication?
After initiating the use of topical agents and titrating pregabalin, I would re-evaluate the effectiveness of the treatment and consider additional nonopioid options. However, in this patient's case, he has cardiac abnormalities and likely cognitive impairments, so weighing the adverse effects of additional anticonvulsants vs opioids is challenging.

Moreover, with the current landscape and fear of opioid-related misuse, abuse, deterrence, side effects, and strict oversight, providers must be extremely cautious when initiating opioids for chronic noncancer-mediated pain.7

It is never an easy decision to prescribe or not prescribe. The provider must determine whether to initiate opioids or consider referral to another provider specializing in pain management.
Based on Jack's medical history, degree of pain, potential side effects of alternatives, and failure of prior treatments, he is an ideal candidate for the use of opioids to improve his quality of life.

Would you give Jack long- or short-acting opioids for his pain?
Many factors such as side effects, polypharmacy, and systemic conditions come into play when choosing the proper opioid regimen.

An initial option would be to start short-acting tramadol, since it has both weak mu-opioid receptors and weakly inhibits the central neuronal reuptake of norepinephrine and serotonin, a potent dual-mechanism of action. However, the side effects and drug-drug interactions could lead to serotonin syndrome and seizures, which require extreme caution.9

In addition, the patient's medical history, time course of pain, and cognitive function should be considered when choosing short-acting vs extended-relief options. Elderly patients with cognitive impairments may not take breakthrough pain medication appropriately or may accidently take additional medication.

Because most of Jack's diabetic pain is chronic in nature and is exacerbated during the evening, one option could be a long-acting around-the-clock medication taken in the evening with subsequent reevaluation. Remember that the starting dose of opioids should be reduced by 50% in elderly patients compared with the general adult population.

However, if a patient with no cognitive impairment has more incident-related pain, an alternate strategy in starting opioids could be to start a low-dose breakthrough pain medication (ie, q6-8hrs pro re nata). Once proven effective and stable, switch to a long-acting around-the-clock regimen.

How often would you monitor Jack for his pain condition and opioid use?
Initial monitoring during an opioid trial would be appropriate within a couple weeks of starting a medication. At the follow-up, discussion should include appropriate dose, frequency, and side effects. Once a stable regimen is established, monthly visits are appropriate. Elderly patients generally have multiple providers, lab work, hospitalizations, procedures, or adjustment in medications by multiple providers treating them. These changes can seriously impact the use and interaction with opioids and would require constant vigilance by the provider and patient to review at each visit.7

In conclusion, when caring for elderly patients suffering from pain, the following topics, reviewed in the case discussions, are extremely important:

• type of pain conditions (ie, neuropathic vs nociceptive pain);

• use of acetaminophen and current recommendations;

• risk of NSAIDs in the elderly population;

• AGS guidelines for opioid initiation in chronic noncancer pain;

• optimal opioid dosing strategy for breakthrough and around-the-clock pain;

• nonopioid alternatives including antiepileptics, antidepressants, and topical agents; and

• risks and monitoring associated with chronic noncancer opioids.

— Ashish R. Udeshi, MD, is an interventional pain specialist with Florida Pain Institute in Merritt Island, Florida, and a board-certified anesthesiologist. He is also a voluntary assistant professor at the University of Miami in the department of clinical anesthesiology.

References
1. Turk DC, Okifuji A. Pain terms and taxonomies of pain. In: Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica's Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:13–24.

2. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57(8):1331-1346.

3. Shega, JW, Morrissey MB, Reid MC. From publication to practice: an interdisciplinary look at the labeling changes for acetaminophen and the implications for patient care. Washington, DC: Gerontological Society of America; 2011.

4. U.S. Food and Drug Administration. Acetaminophen Prescription Combination Drug Products with more than 325 mg: FDA Statement - Recommendation to Discontinue Prescribing and Dispensing. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm381650.htm. Published January 14, 2014. Accessed August 8, 2014.

5. Zempsky W. Use of topical analgesics in treating neuropathic and musculoskeletal pain. Pain Medicine News. 2013;Sept:1-4.

6. Fine PG, Portenoy RK. A Clinical Guide to Opioid Analgesia. New York, NY: Vendome Group, 2007.

7. Manchikanti L, Abdi S, Atloris S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2 - guidance. Pain Physician. 2012;15(3 Suppl):S67-116.

8. Huizinga MM, Peltier A. Painful diabetic neuropathy: a management-centered review. Clin Diabetes. 2007;25(1):6-15.

9. Haslam C, Nurmikko T. Pharmacological treatment of neuropathic pain in older persons. Clin Interv Aging. 2008;3(1):111-120.

10. Zur E. Topical treatment of neuropathic pain using compounded medications. Clin J Pain. 2014;30(1):73-91.

11. Lindsay TJ, Rodgers BC, Savath V, Hettinger K. Treating diabetic peripheral neuropathic pain. Am Fam Physician. 2010;82(2):151-158.