Author: Suzanne Novak, MD, PhD
As noted in our previous blogs, “The Role of Opioids in Chronic Pain Management” (Parts I and II), the use of opioids to treat chronic pain is controversial, and there is little evidence opioids control chronic pain. There is evidence of serious potential harms from use of this class of drugs. In Part III, Dr. Novak discusses these topics.
- Pain classifications as criteria for prescribing pain medications
- Steps in identifying the type of pain the patient is experiencing
- Medications suggested for different types of pain
- Suggested steps for prescribing
Pain classifications as a background for prescribing pain medications
There are three basic types of pain which are differentiated by involvement of the somatosensory nervous system. This system is concerned with the perception of touch, pressure, pain, temperature, position, movement, and vibration.
- Nociceptive pain: This pain occurs when there is actual damage to non-neural tissue (i.e., tissue not related to nerves or the nervous system) that activates nerve pathways to result in pain.[1] This pain is generally localized and constant. Nociceptive pain is often found in acute injuries such as sprains, bone fractures, burns, and surgeries. Chronic nociceptive pain can result from arthritis/degenerative changes (e.g., facet joint osteoarthritis and spondylosis) or myofascial pain. When related to the spine, this is often called mechanical back pain.
- Neuropathic pain: This pain is caused by injury or malfunction of the somatosensory nervous system. An actual nerve injury is not required.1 Multiple mechanisms are often involved, and patients may not have objective clinical findings. Pain is often described as burning, lancinating, or with electric shock qualities. Neuropathic pain is heterogenous in nature, which can make it difficult to diagnose. Diagnostic testing may be inconclusive or even inconsistent. A diagnosis may ultimately rely on clinical judgement. Neuropathic pain can be central or peripheral.[2] Examples of neuropathic pain not generally related to an injury include peripheral neuropathy (e.g., that secondary to diabetes, alcohol, vitamin deficiency, other toxins, or hepatitis), painful postherpetic neuropathy, multiple sclerosis, and stroke. Carpal tunnel syndrome and other nerve entrapment syndromes can cause neuropathic pain. Other neuropathic pain conditions include radiculopathy and post-amputation pain. Neuropathic pain is frequently chronic, and may not be fully reversible.
- Mixed pain results from a mixture of nociceptive and neuropathic pain. As an example, myofascial pain has been considered to be nociceptive (due to input from muscle receptors), but abnormal muscle activity can cause additional pathology which is neuropathic, resulting in a mixed pain picture. Some have suggested that knee osteoarthritis can also present in a mixed pain picture.[3]
Steps in identifying the type of pain the patient is experiencing
- A thorough history and physical should be taken for any pain patient for whom medications are planned. The patient should describe the pain in his or her own words (e.g., constant, aching, burning, lancinating). Imaging and other diagnostic procedures, such as electrodiagnostic testing, may be required.
- Identifying comorbid conditions which are potential pain generators is One of the most important conditions is diabetes, with at least a 50% potential for a presentation of neuropathic pathology depending on the stage of the disease. The primary treatment for diabetic neuropathy is improved glucose control. Diabetic neuropathy may be missed, particularly in patients involved in litigation.
- Identifying psychological overlay can be important in chronic pain patients, and may require identifying the cause of an injury.
Medications suggested for different types of pain
Nociceptive pain:
First line:
- NSAIDs
The first-line medication recommended for nociceptive pain is a non-steroidal anti-inflammatory (NSAID). Over-the-counter products include naproxen and ibuprofen. There is no research to suggest any NSAID is always superior over another for pain control. NSAIDs have multiple side effects, and should be given at the lowest effective dose for the shortest duration consistent with a patient’s treatment goals.
- Gastrointestinal (GI) effects: These may present in a range from mild heartburn type symptoms to serious ulceration (including bleeding). There are risk factors for the latter, and these include age over 65, a history of GI ulceration or bleeding, or a history of taking other medications that when used together increase the chance of serious symptoms (e.g., aspirin, corticosteroids, or other NSAIDs). When these risk factors are present, an NSAID should be used with caution. The recommended product is a selective cyclooxygenase (COX)-2 drug such as celecoxib (Celebrex®).
- Cardiac effects: All NSAIDs appear to have the potential to produce adverse cardiac effects. In 2015, the FDA strengthened a warning that all non-aspirin NSAIDs can increase the risk of heart attack, and increase the risk of heart failure. [4] NSAIDs should be used cautiously in patients with cardiac disease. Some research suggests the use of naproxen or celecoxib in patients with cardiac disease.[5]
- Hypertension: NSAIDs should be used cautiously in patients with hypertension, as all NSAIDs have the potential to raise blood pressure in susceptible patients. If an NSAID cannot be stopped, blood pressure meds should be adjusted.
- Renal effects: NSAIDs should be used with caution in patients with kidney disease, and should be avoided in patients with advanced disease. Stages of kidney disease are determined, in part, by a lab test call estimated glomerular filtration rate (eGFR). In the presence of a level below 30 cc/min (stage 4 or 5 kidney disease), NSAIDs should be avoided. Any use in a patient with stage 3 disease (eGFR between 30 cc/min and 59 cc/min) should include careful assessment of risks and benefits.
An alternative to an NSAID can be acetaminophen (particularly in an acute setting). It is generally only after failure of an NSAID that an opioid can be suggested with caution.
Second line
- Antidepressants
Duloxetine (Cymbalta®) has been recommended on a case-by-case basis for chronic low back pain, knee osteoarthritis, and fibromyalgia.
Neuropathic pain: Medication management is complicated in neuropathic pain due to the heterogeneous presentation. Opioids are rarely successful in treating neuropathic pain and rarely are recommended. These medications are recommended:
First line:
- Antidepressants: Two classes of antidepressants are considered first-line treatment for neuropathic pain.
- Tricyclic antidepressants (TCAs): Examples include amitriptyline, imipramine, nortriptyline, and desipramine. These drugs have a long history of use for chronic pain, but have numerous side effects. These include sedation, risk of falls, and anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation, and dizziness). This class of drugs should not be used in patients with heart disease.
- Serotonin and norepinephrine reuptake inhibitors (SNRIs): Duloxetine (Cymbalta®) is FDA-approved for diabetic neuropathy, and use is extrapolated to other neuropathic pain states. Venlafaxine (Effexor®) is recommended off label for fibromyalgia, and diabetic neuropathy. There is no high-quality evidence to support the general use of duloxetine for radiculopathy, but trials for individual patients are common.
- Anticonvulsants: The most common anticonvulsants used for chronic neuropathic pain are gabapentin (Neurontin®) and pregabalin (Lyrica®). These drugs are FDA-approved for postherpetic neuralgia, fibromyalgia, and diabetic neuropathy. Pregabalin is also FDA-approved for neuropathic pain associated with spinal cord injury. Trial use for other neuropathic pain that the FDA-approved conditions is extrapolated. The price of pregabalin has dropped precipitously since a generic was introduced.
Second line
A second line choice for neuropathic pain is Lidoderm (lidocaine 5% transdermal patch). This drug was approved as an orphan drug for pain associated with postherpetic neuralgia. It is recommended off-label for localized peripheral pain.
Third line
Opioids are the last option for neuropathic pain. Use is discussed in the previous blogs, “The Role of Opioids in Chronic Pain Management” (Parts I and II).
Drugs generally not recommended
NSAIDs rarely are recommended for neuropathic pain, unless a component of nociceptive pain is suspected.
Mixed pain: If neuropathic pain is considered a component of diagnoses generally considered nociceptive (e.g. low back pain or arthritis of the knee), products for neuropathic pain may be tried.
Suggested steps in prescribing
The following steps were followed in a drug treatment plan.
- One drug is tried at a time.
- A trial of a drug is generally 4-6 weeks.
- Clinical improvement is generally considered 30% improvement in pain. Function is considered by many as a more important outcome, and 30% is again recommended in terms of improvement.
- Assessment of improvement in symptoms with a medication should be ongoing.
- A complete drug list of all medications prescribed, including for conditions other than pain, should be maintained to allow evaluation of drug-drug interactions.
- A complete list of outside medical conditions should be maintained. This allows evaluation of drug-disease interactions.
- Evaluation of the risks versus benefit of each drug should be documented.
Polypharmacy, the simultaneous use of multiple drugs, occurs frequently. When detected, it may be reasonable to ask a clinician to reduce or eliminate a drug (with appropriate weaning) to determine if the drug is effective. This may be particularly important if there is evidence of drug-drug or drug-disease interactions.
Conclusion
There are medication options to opioids, although choice and effect is limited. This blog has briefly reviewed the available medications and their indications for different types of pain. This will hopefully aid in pain medication management when used with the previous blogs in this series.
[1] IASP. Available at: https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698. Accessed 5/29/2020.
[2] Nicholson B. Differential diagnosis: nociceptive and neuropathic pain. Am J Manag Care. 2006 Jun;12(9 Suppl): S256-62.
[3] Hasegawa M, Tone S, Naito Y, Wakabayashi H, Sudo A. Prevalence of Persistent Pain after Total Knee Arthroplasty and the Impact of Neuropathic Pain. J Knee Surg. 2019 Oct;32(10):1020-1023.
[4] (FDA, 2015, Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory). Accessed 5/29/2020.
[5] Grosser T, Ricciotti E, FitzGerald GA The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs. Trends Pharmacol Sci 2017 Aug;38(8):733-748
Author
Dr. Novak is a board-certified anesthesiologist and has her PhD in Pharmacy Administration. She is president of Austin Outcomes Research, Inc., a healthcare consulting and utilization review firm with multiple national carriers and legal firms as clients. She is the lead author of the Pain Chapter of the ODG Treatment Guidelines and is a clinical assistant professor at the College of Pharmacy at the University of Texas at Austin where she is active in the Pharmacy Practice Division.