Chronic Pain Management: A Healthcare Professional's Guide
Medically reviewed on Mar 12, 2018 by L. Anderson, PharmD
Chronic Pain: It's Universal
Pain is the top reason a patient seeks medical care, and it's the most common complaint of people worldwide. In fact, at least 1 out of every 5 patients is dealing with some type of nonmalignant chronic pain - whether it be arthritis, low back pain, or migraine headaches -- pain can interfere with work, sleep and one's general quality of life.
With greater concerns about overprescribing pain relief medications like opioids, and a detailed Guideline for Prescribing Opioids for Chronic Pain issued by the CDC, what's a health care provider to do?
Here's a general overview of general chronic pain medication options, non-drug options, and how to ensure your patient gets adequate pain relief while minimizing their risk for adverse effects and addiction.
Pain Management: It's a Joint Effort
Pain management is a combined effort - not only pharmacologically, but also with a healthcare team, the patients, and members of the patient's family.
A multidisciplinary team of doctors, nurses, pharmacists and other allied health professionals can work together to ensure a better outcome for the patient. Caregivers should be involved with pain management education, treatment plans and goals.
Importantly, drug treatment should encompass a stepwise approach, utilizing multiple agents when appropriate to take advantage of synergistic mechanism of actions, lower dosing strategies, and reduced side effects.
Know the Type and Level of Pain
Chronic nonmalignant pain is defined as persistent pain lasting after six months, beyond the usual course of disease or injury, not related to cancer.
A combined approach to pain is important: identifying the type of pain -- nociceptive (tissue injury), neuropathic (nerve-related or nervous system injury), or mixed -- is paramount to determining treatment options.
Quantifying the level of pain using a visual analog scale may also aid in treatment decisions.
Which Drugs Can Be Used for Pain?
Medication class options for chronic pain are varied and include many other agents besides opioids:
- Nonopioid analgesic agents, such as topical analgesic agents, acetaminophen and NSAIDs
- TCA antidepressants
- SNRI antidepressants
- GABA Analog Anticonvulsants
- Muscle relaxants
While many drugs are used successfully as either single agents or combined treatments, the response to pain therapy varies widely among patients and requires regular monitoring and follow-up. Per CDC guidelines, nonopioid therapy is preferred for chronic pain outside of active cancer, palliative, and end-of-life care.
General Treatment Strategies
Utilizing a consistent set of principles when implementing pain management in patients can be helpful in the clinic.
- Use most efficient/preferable routes of drug administration.
- Consider a fixed-dose schedule instead of "as needed" pain relief.
- Follow stepwise administration of medicine from non-opioids to opioids, plus nondrug therapy early-on when appropriate.
- Dosing is patient-specific; use the lowest possible dose in all cases.
- Management of drug side effects (ie, nausea) and psychiatric issues (ie, depression) should occur proactively.
- Assess for adherence, possible drug abuse, and consider written treatment agreements and urine drug screening in select cases.
Guidelines for Chronic Pain Management
While pain management in any one patient requires the clinical expertise of the treating physician and other healthcare professionals, guidelines can help to answer questions regarding drug treatment, effectiveness of patient contracts and urine drug testing, and discontinuation of therapy.
In February 2016, FDA announced a sweeping review of the agency’s approach to opioid medications to evaluate ways to reverse the epidemic of narcotic abuse while still ensuring access to much-needed pain relief for those who truly need it.
- The CDC has issued 2016 guidelines for Prescribing Opioids for Chronic Pain.
- Cochrane for Clinicians, an evidence-based group, has published Opioid Therapy for Chronic Noncancer Pain.
- Chou, et al has released an evidence report The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain from AHRQ.
- In 2017, the American College of Physicians (ACP) released recommendations in the Annals of Internal Medicine for first-line, non-drug therapy for low-back pain.
Non-Opioid Analgesics: Acetaminophen
Non-opioid medications are typically first-line medications for chronic, non-malignant, nociceptive pain. Select agents within this group include acetaminophen, NSAIDs and COX-2 inhibitors. However, all of these agents have risks themselves.
Acetaminophen (Tylenol) is often recommended for noninflammatory chronic pain conditions but chronic use at high doses can lead to severe liver toxicity. In January 2014 the FDA required all prescription acetaminophen combination products, such as combined products with opioids, to contain no more than 325 mg of acetaminophen to lessen incidence of unintentional acetaminophen overdose. Combined use with alcohol can also hasten liver disease. Doses should not exceed 3 to 4 grams per day. Acetaminophen does not have appreciable, if any, anti-inflammatory action but may work for knee osteoarthritis in some patients.
Non-Opioid Analgesics: NSAIDs
NSAIDs, such as ibuprofen or naproxen, are effective anti-inflammatory pain relievers available OTC and at a low cost. However, concerns exists with side effects such as dyspepsia/GI bleeds, cardiovascular risks, and kidney impairment. The elderly may be at highest risk. In patients with heart risks, an FDA panel has determined that naproxen has no advantage over other NSAIDs.
NSAIDs can also interfere with the cardioprotective effect of low-dose aspirin by competitive inhibition of platelet cyclo-oxygenase, according to drug interaction research. Patients receiving low-dose aspirin for cardioprotection should avoid the regular use of ibuprofen and other NSAIDs. Occasional use of up to 400 mg ibuprofen is acceptable with immediate-release, low-dose aspirin; however, ibuprofen should not be taken within 8 hours before or 30 minutes after the aspirin dose.
Several guidelines, including the Beers Criteria, recommend that oral use of NSAIDs in the elderly should be avoided when possible due to possible GI toxicity. Topical NSAIDs are available for specific osteoarthritis (OA) joint pain and might be a reasonable option in these patients. Topical diclofenac (Pennsaid, Flector Patch, Voltaren Gel) is available commercially.
Studies suggest topical diclofenac preparations are effective for OA pain and pain management may be similar to that achieved with oral NSAIDs. Topical NSAIDs should have a safer risk profile than oral NSAIDs due to lower systemic absorption. However, oral NSAIDs may be considered for chronic use if combined with gastroprotective (proton-pump inhibitor or misoprostol).
More Topicals: Capsaicin
Besides topical NSAIDs, there are other options for topical treatment of pain. Capsaicin (Zostrix, Icy Hot Arthritis Therapy, Salonpas) is the active ingredient that gives heat to chili peppers. It has been used as a topical analgesic to sooth pain in arthritis and for neuralgia due to shingles (herpse zoster).
It comes in many forms including OTC creams, lotions, gels and and a prescription patch known as Qutenza for postherpetic neuralgia.
Qutenza, applied by a healthcare provider, can provide up to 12 weeks of reduced pain following a single one-hour application. Up to four patches may be used at any one time and treatment may be repeated every three months if needed. Qutenza is unlikely to cause drowsiness or have drug interactions.
A Safer NSAID?
Another option to treat chronic inflammatory pain but lessen side effect risk is with celecoxib (Celebrex), a COX-2 inhibitor that treats pain similarly to the nonselective NSAIDs, but with lower GI risk. However, higher doses of celecoxib (>200 mg) are linked with a higher risk for adverse cardiovascular outcomes as with other NSAIDs.
Another option is choline magnesium trisalicylate which does not interfere with platelet aggregation, but still may cause GI distress. In patients who do not tolerate or who have limited effectiveness with one NSAID, it is reasonable to try another, as results can be variable.
Anticonvulsants for Neuropathic Pain
Anticonvulsants, which inhibit neurotransmitter release, have been shown effective for:
- post-herpetic neuralgia
- diabetic neuropathy
Pregabalin has a quicker onset of action than gabapentin, but is classified as a schedule V controlled substance by the DEA due to possible euphoric effects.
Dosing of these drugs should be started low and titrated up gradually to avoid CNS side effects; it may take several months for optimal pain control. These drugs are considered first line over opioids or tramadol for neuropathic pain management.
Antidepressants For Pain: TCAs
The tricyclic antidepressants (TCAs) have long been used for neuropathic types of pain. Depression may also be a co-morbid condition with many chronic pain states, and this class may lend efficacy to treatment via an antidepressant effect.
Common TCAs used for neuropathic pain include:
- amitriptyline (Elavil)
- doxepin (Sinequan)
- imipramine (Tofranil)
- nortriptyline (Pamelor)
- desipramine (Norpramin).
All of these agents are available in cost-saving generics.
Typically, doses should be slowly titrated and given close to bedtime. Full effectiveness can take upwards of 6 to 8 weeks in some patients. Anticholinergic side effects, like dry mouth, sedation, confusion, and dizziness may be transient side effects. If a TCA must be used in an elderly patient, start with the lowest possible dose at bedtime and choose agents with lower anticholinergic effects like desipramine.
Taper all TCAs slowly to discontinue.
Antidepressants For Pain: SNRIs
The serotonin norepinephrine reuptake inhibitors (SNRIs) have shown benefit for treatment of neuropathic pain. Venlafaxine (Effexor) can be used for treatment of diabetic neuropathy, but should be used with caution if cardiac disease exists.
Duloxetine (Cymbalta) has many uses for pain including fibromyalgia, chronic low back pain and osteoarthritis. However, some studies for back pain have not provided long-term, positive results. A trial of duloxetine may be appropriate, especially in patients with co-morbid anxiety or depression.
Side effects can include dry mouth, insomnia, nausea, fatigue or drowsiness, and constipation.
Muscle Relaxants for Chronic Pain
Skeletal muscle relaxants, also called antispasmodics, can be used for painful muscle spasms that may occur with musculoskeletal conditions like neck or low back pain.
In the US, carisoprodol is classified as a schedule IV controlled substance in most states due to potential for abuse.
The Lidocaine Patch
Lidoderm (lidocaine patch 5%) is a topical patch prescribed to treat post-herpetic neuralgia.
Only apply the patch to intact (non-blistered) skin to avoid excessive absorption of lidocaine. Up to 3 patches can be applied only once for up to 12 hours per day. Cut the patches to size and use the lowest dose possible. Mild, localized but transient skin reactions may occur after application; skin reactions reactions are generally mild and resolve within a few minutes to hours.
Lidocaine topical patch is also available in a cost-saving generic form.
In February 2018, the FDA has approved ZTlido (lidocaine topical system 1.8%), a transdermal anesthetic formulation for the treatment of pain associated with postherpetic neuralgia (PHN) that can occur after an episode of shingles (herpes zoster).
ZTlido, from Sorrento Therapeutics and Scilex, offers a proprietary adhesion technology, a 12-hour wear, and efficient lidocaine delivery, even during exercise. ZTlido only requires 36 milligrams (mg) per patch versus 700 mg per patch of Lidoderm (lidocaine patch 5%) to achieve the same therapeutic dose of drug. In comparative pharmacokinetic studies, ZTlido demonstrated bioequivalence with Lidoderm. Side effects with ZTLido may include transient skin reactions such as blisters, a burning sensation, redness, or irritation.
Nonmalignant Chronic Pain: Options
Prescription opioids for pain are responsible for rising rates of overprescribing, addiction, and overdose, even in people who have previously overdosed.
In general, non-opioids like NSAIDs and acetaminophen, adjunctive therapies, and exercise/physical therapy are preferred for chronic pain.
Narcotic analgesics should only be considered if the anticipated benefits with regard to pain relief and function outweigh risks to the patient taking into account an individual's history of abuse, likelihood of overdose, family/social interactions, and drug diversion probability.
Opioids: The Choices Are Many, But Choose Wisely
For patients with severe pain, often cancer-related chronic pain, prescription opioids may be appropriate. Pain that is short-lived (3-5 days) can be approached with physical therapy, exercise, NSAIDs, and acetaminophen. If opioids are prescribed, low doses and short-term therapy should be used. Combined use of opioids and nonopioids may be preferred.
Be aware that many agents are extended-release and not appropriate for opioid-naive patients or patients needing pain treatment on an as-needed basis. Review dosing closely, and educate the patient on dosing and risks of sedation, respiratory depression, and possible death.
Examples of opioid analgesics include:
- Oxycodone (Oxycontin, Roxicodone, Roxybond)
- Hydrocodone (Hysingla ER, Zohydro ER)
- Acetaminophen/Hydrocodone(Lortab, Lorcet, Vicodin)
- Tramadol (Ultram ER, Ultram, Ryzolt)
- Acetaminophen/Codeine (Tylenol with Codeine)
- Acetaminophen/Benzhydrocodone (Apadaz)
- Fentanyl (Duragesic, Actiq)
- Morphine (MS Contin, Kadian)
- Hydromorphone (Dilaudid, Exalgo)
- Methadone (Dolophine, Methadose, Methadone Diskets)
- Oxymorphone (Opana)
- Tapentadol (Nucynta)
Opioids: Mechanism and Side Effects
Opioids work by reducing nerve excitability that leads to the pain sensation by binding to opioid receptors in the brain and elsewhere.
There are 3 main types of opioid receptors: Mu, Delta, and Kappa. These receptors either aid with the opening of potassium channels (causing hyperpolarization) or block the calcium channel, preventing the release of excitatory neurotransmitters like substance P that are involved with pain.
Opioids are linked with a wide array of side effects, such as:
- respiratory depression
- withdrawal symptoms
Opioid Side Effect Prevention
Due to the wide variety of side effects with opioids for chronic severe pain, adherence can be an issue and lead to inadequate pain management. Although some side effects are transient and will subside with time, others may be long lasting.
- For pruritis and emesis, antihistamines and antiemetics should be instituted early on.
- For opioid-induced constipation, use of a stool softener like docusate (Colace), a laxative (senna), or an osmotic laxative like lactulose or polyethylene glycol (MiraLAX) can be used.
Prescription agents approved for opioid-induced constipation (OIC) include:
Opioids Inappropriate for Chronic Low Back Pain
Low back pain is one of the most common chronic pain syndromes treated in the US. Long-term back pain effects 26 million Americans aged 20 to 64, according to the American Academy of Pain Medicine.
In a 2015 study published in the Journal of the American Medical Association, researchers found that 500 mg of naproxen alone was as good as treating low back pain with 5 mg oxycodone and 325 mg acetaminophen (Percocet) plus naproxen, or a muscle relaxant like 5 mg of cyclobenzaprine (Amrix) plus naproxen.
Researchers noted some patients may need to optimize their regimen to achieve success with NSAIDs alone. Nonetheless, regardless of the treatment, nearly two-thirds of patients had significantly less pain and better movement one week after starting treatment.
Another report published in the March 6, 2018 issue of the Journal of the American Medical Association (JAMA) came to a similar conclusion: that opioids were no better for back pain but came with significantly more risks than other pain medications or treatments. Other options included: exercise, acetaminophen (Tylenol), and nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil, Motrin), naproxen (Aleve), amitriptyline or gabapentin, topical analgesics such as lidocaine, duloxetine (Cymbalta) or pregabalin (Lyrica), or the narcotic tramadol (Ultram).
Tramadol: Not Risk Free
Tramadol (Ultram, Ultram ER, ConZip, Rybix ODT, Ryzolt) is a commonly prescribed pain medication that has partial action at the mu opioid receptor, plus it is a serotonin and norepinephrine reuptake inhibitor. Tramadol was thought to be at lower risk for addiction, but it has been linked with drug abuse and misuse, dependence, and even fatal overdoses.
To address these concerns, in 2014 the DEA placed all forms of tramadol into schedule IV of the Controlled Substances Act (CSA).
Tramadol is related to other opioids and can lead to:
- psychological and physical dependence
- drug-seeking behavior
- withdrawal symptoms.
Withdrawal symptoms may occur if tramadol is abruptly stopped. Dose reduction of long-term tramadol use should be slowly tapered. The side effect profile is similar to other opioids, but seizure risk may be elevated in some patients.
Methadone: An Overdose Waiting to Happen?
Methadone, a potent opioid used for heroin addiction treatment and severe cancer pain, is also increasingly used for severe chronic non-cancer pain.
According to a 2012 CDC report, methadone was involved in one-third of opioid pain relief deaths in the US, even though only representing a small fraction of prescriptions. FDA has also issued a Public Health Advisory warning of methadone overdoses.
Methadone is useful for chronic severe pain because it has a long duration of action, low cost, and availability in liquid form. However, its long and variable half-life, up to 5 days, can lead to accumulation and fatal respiratory depression, arrhythmia, and accidental death.
Methadone should only be prescribed by physicians experienced with its use, with close patient monitorin, education, and adherence to dosing guidelines.
Abuse-deterrent formulations of opioids are increasingly being developed as one method to prevent abuse and overdose of immediate-release and extended-release opioids. Chewing, crushing, snorting, or injecting are some of the more common ways these potent opioids are abused.
"Abuse-deterrent" means that the medication has been developed using FDA guidelines to exhibit properties that can lower, but not totally eliminate, the ability to abuse the drug. Clinically, these agents are used for around-the-clock, severe pain treatment and not on an "as needed" basis.
Examples of abuse-deterrent forms include:
- Oxycontin (oxycodone [reformulated])
- Embeda (morphine/naltrexone)
- Hysingla ER (hydrocodone)
- Targiniq ER (oxycodone/naltrexone)
- Troxyca ER (naltrexone/oxycodone)
- Xtampza ER (oxycodone)
- Zohydro ER (hydrocodone)
- [Roxybond](https://www.drugs.com/cdi/roxybond.html) (oxycodone immediate-release)
Non-Drug Therapy for Chronic Pain
When possible, non-drug therapy for chronic pain should be used as a first-line treatment, especially for low back pain, according to 2017 guidelines put out by the American College of Physicians (ACP).
If not successful, non-drug therapies may need to be combined with non-opioid drugs like NSAIDs or as an adjunct to opioids to lower required doses and shorten treatment times.
Examples of non-drug options include:
Finished: Chronic Pain Management: A Healthcare Professional's Guide
- Opioids Not Best Option for Back Pain, Arthritis, Study Finds. Drugs.com. March 6, 2018. Accessed March 12, 2018 at https://www.drugs.com/news/opioids-not-best-option-back-pain-arthritis-study-finds-68906.html
- The US Centers for Disease Control and Prevention (CDC). CDC Guideline for Prescribing Opioids for Chronic Pain. March 15, 2016. Accessed March 12, 2018 at http://www.cdc.gov/drugoverdose/prescribing/guideline.html
- Chou R, Turner JA, Devine E, et al. The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276-286. doi:10.7326/M14-2559. Accessed March 12, 2018 at http://annals.org/article.aspx?articleid=2089370
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- Reuben DB, Alvanzo AA, Ashikaga T, Bogat GA, Callahan CM, Ruffing V, et al. National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain. Ann Intern Med. 2015;162:295-300. doi:10.7326/M14-2775. Accessed March 12, 2018 at http://annals.org/article.aspx?articleid=2089371
- The American Academy of Pain Medicine. Use of Opioids for the Treatment of Chronic Pain. February 2013. Accessed March 12, 2018 at http://www.painmed.org/files/use-of-opioids-for-the-treatment-of-chronic-pain.pdf
- American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 63:2227–2246, 2015. Accessed March 12, 2018 at http://onlinelibrary.wiley.com/doi/10.1111/jgs.13702/full
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- Rosenquist E. Overview of the treatment of chronic pain. Up To Date. Updated February 16, 2016 at http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic-pain
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