Chronic Pain Management: A Healthcare Professional's Guide
Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on June 5, 2021.
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 US Centers for Disease Control and Prevention (CDC), what's a health care provider to do? Ongoing pain is an issue that millions of Americans deal with every day.
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 joint effort - not only when prescribing drug treatment, but also with the interactions of the patient, the patient's family, and your healthcare team colleagues.
- 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.
- The risk of addiction, diversion, or misuse of opioids by the patient and within the patient's household should be assessed before prescribing pain treatment.
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 is paramount to determining treatment options.
- nociceptive (tissue injury)
- neuropathic (nerve-related or nervous system injury)
- central pain sensitization (damage to the CNS, with pain sensitization)
- or mixed
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 the optimal dosing schedule and length of treatment.
- 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, family support or risk for diversion, 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.
- The CDC has issued guidelines for Prescribing Opioids for Chronic Pain.
- Cochrane for Clinicians, an evidence-based group, has published Opioid Therapy for Chronic Noncancer Pain.
- Chou and colleagues released an evidence-based report The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain from AHRQ.
- 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 such as celecoxib. However, all of these agents have inherent risks themselves.
Acetaminophen (Tylenol) is often recommended for noninflammatory chronic pain conditions but chronic use at high doses can lead to severe liver toxicity.
- The FDA now requires 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. Acetaminophen doses should not exceed 3 to 4 grams total per day. Patients should be thoroughly counseled on acetaminophen maximum doses and combined use with excessive alcohol.
- 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.
- Anjeso is the first once-daily intravenous (IV) COX-2 preferential NSAID for pain, used in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics
- Anjeso is given as a 30 mg once-a-day intravenous (IV) bolus push; rescue pain medication may be needed in the first 2 to 3 hours after the dose due to a delayed onset of action.
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 (Flector Patch, Voltaren Arthritis Pain Gel) is available commercially. Voltaren Arthritis Pain is an over-the-counter options approved in Feb 2020.
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) when used in the elderly. Assess risk factors for older patients before recommending or prescribing NSAIDs.
More Topicals: Capsaicin
Besides topical NSAIDs, there are other options for topical treatment of pain. Capsaicin (Zostrix, Salonpas Hot Patch, PainBloc 24) 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 over-the-counter (OTC) forms including creams, lotions, gels and patches.
Capsaicin is also available as a prescription patch known as Qutenza for postherpetic neuralgia (nerve pain) in people who have had shingles, and for nerve pain associated with diabetic peripheral neuropathy of the feet.
- Qutenza patches must be applied by a healthcare provider. It 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. Do not use Qutenza if you are allergic to chili peppers.
- The most common side effects are application site redness, pain and itching.
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
Immediate-release pregabalin (Lyrica) is also approved to treat fibromyalgia, but Lyrica CR does not have this indication.
- The Gralise brand of gabapentin is used for the management of neuropathic pain from shingles only, and not for epilepsy. In addition, Gralise cannot be interchanged with other gabapentin products.
- The Horizant brand of gabapentin is used to treat diabetic nerve pain, pain from shingles, as well as restless legs syndrome (RLS).
- The Neurontin brand of gabapentin is used to treat seizures in patients at least 3 years old, in addition to neuropathic pain from shingles (postherpetic neuralgia).
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. 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.
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:
- 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, Irenka) 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 its potential for abuse.
The Lidocaine Patch for Post-Herpetic Neuralgia
Lidoderm (lidocaine patch 5%) is a topical patch prescribed to treat post-herpetic neuralgia. Lidocaine topical patch is also available in a cost-saving generic form.
- 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 are generally mild and resolve within a few minutes to hours.
In February 2018, the FDA 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 offers a 12-hour wear time 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.
- 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 addiction, and overdose, even in people who have previously overdosed.
Opioid narcotics like morphine and oxycodone remain an option, but are not the preferred treatment in noncancer-related pain. 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
- 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 to 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, risks of alcohol use, respiratory depression, and possible death.
Common names of opioid analgesics include:
- oxycodone (Oxycontin, Roxicodone)
- hydrocodone (Hysingla ER, Zohydro ER)
- acetaminophen/hydrocodone (Lortab, Lorcet, Vicodin)
- tramadol (Ultram, ConZip, Qdolo)
- acetaminophen/benzhydrocodone (Apadaz)
- fentanyl (Duragesic, Actiq)
- morphine (MS Contin, Kadian)
- methadone (Methadose)
- tapentadol (Nucynta, Nucynta ER)
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. Low back pain effects roughly 31 million Americans at any given time. But opioids are not typically a good option for low back pain.
In a study published in the Journal of the American Medical Association (JAMA), 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 opioid tramadol (Ultram, ConZip, Qdolo). Tramadol can be linked with abuse similar to other opioids and should be used only short-term when possible.
Tramadol: Not Risk Free
Tramadol (Ultram, ConZip, Qdolo) 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 previous 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 previously 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 monitoring, 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:
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 and symptoms of insomnia. If not successful, non-drug therapies may need to be combined with non-opioid drugs like NSAIDs or as an adjunct to short-term opioids to help lower required doses and shorten treatment times.
Examples of non-drug options include:
Finished: Chronic Pain Management: A Healthcare Professional's Guide
In 1995, tramadol was FDA-approved as a narcotic pain reliever thought to be associated with a lower risk of drug abuse. But in a report a decade later, abuse-related tramadol ER...
Society tends to treat menopause as a disease; something to be avoided at all costs. But menopause can be positive. No more monthly mood swings, period accidents, or pregnancy worries. Self-confidence and self-knowledge...
- Gomes T, Juurlink DN, Antoniou T, et al. Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS Med. 2017;14(10):e1002396. doi:10.1371/journal.pmed.1002396
- Gomes T, Greaves S, van den Brink W, Antoniou T, et al. Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control Study. Ann Intern Med.; 169:732–734. doi: 10.7326/M18-1136
- Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015;314(15):1572–1580. doi:10.1001/jama.2015.13043
- The US Centers for Disease Control and Prevention (CDC). CDC Guideline for Prescribing Opioids for Chronic Pain. http://www.cdc.gov/drugoverdose/prescribing/guideline.html
- McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 2013 Dec;14 Suppl 1:S35-9. doi: 10.1111/pme.12288. DOI: 10.1111/pme.12288
- O’Donnell J, Vogenberg FR. Applying Legal Risk Management To the Clinical Use of Methadone. P and T. 2011 Dec; 36(12): 813-814, 821-822. PMID: 22346315