Higher-Risk Pain Treatments: Benefits, Risks, and Tips


Treatment Name and Description

Benefits of common drugs


Use/monitoring Tips

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Alleviates pain with first dose but repeated doses for a few days maximize the anti-inflammatory effect. Ceiling effect: higher doses often don’t relieve more pain, just increase undesired effects. Tell healthcare provider (HCP) if using daily for more than 2 weeks. Protect GI tract with food and a full glass of water. Don’t take with other NSAIDs, steroids or drugs affecting clotting unless instructed to by prescriber. Avoid with a history of peptic ulcers, symptomatic heart failure, or chronic kidney disease.

Commonly used examples:

  • Acetylsalicylic acid (Aspirin) >325mg
  • Ibuprofen, Naproxen 
  • Celecoxib
  • Indomethacin, ketorolac
  • Salsalate (Disalcid)

Aspirin: good anti-inflammatory and antiplatelet effects. Common drug interactions and blood-thinning effects last for days.

Risks (i.e., GI ulceration or bleeding; kidney/heart disease, neurotoxicity) outweigh benefits of daily use >325mg.

Report other meds taken, GI symptoms; signs of internal bleeding; edema, cough, fatigue or urine changes. Discard aspirin smelling like vinegar.

Ibuprofen, Naproxen: readily available without prescription. Meloxicam and others require a prescription. Best effect after several days of use.  

Increases blood pressure and cardiac/renal problems.   Greater risk of serious GI, CV, or renal problems over  age 75 years. May trigger asthma in some people.

Report signs/symptoms as above. Avoid ibuprofen with cardioprotective aspirin.  Frequent blood pressure checks and annual tests of CV, renal and hepatic function. Periodic dose reduction trial.  

Celecoxib: does not increase bleeding risk. Dosing once a day is possible. Fewer GI side effects the first year of use.  May be better for patients with NSAID-sensitive asthma.

Slightly higher risk of heart or kidney problems than other NSAIDs.

Initial dose twice daily, then once daily if effective. Protect GI tract from ulcers if taking aspirin or used daily > 1 year. Same monitoring and symptom reporting as above.

Indomethacin or ketorolac

may better reduce pain in some inflammatory disorders.

Higher risk of bleeding, kidney or central nervous system toxicity than other NSAIDs. 

For short term use (< 8 days). Avoid or reduce dose for older adults.  Protect GI tract and report above signs/symptoms.

Salsalate (Disalcid) has less GI bleeding risks. Twice daily dosing possible (may improve adherence).

GI side effects or renal toxicity may occur.  May reduce insulin resistance

Generally, better tolerated than other NSAIDs, with same risks and reportable signs/symptoms.

Key: GI = Gastrointestinal; CV = Cardiovascular


Treatment Name and Description





Takes weeks at therapeutic dose to achieve the best analgesic effect, and months to best improve mood.

Commonly used examples:

  • Tricyclic antidepressants [TCAs] (e.g., amitriptyline, nortriptyline, imipramine, clomipramine, doxepin)
  • Serotonin and Norepinephrine Reuptake Inhibitors [SNRIs] (e.g., Duloxetine, Venlafaxine)

May interact with CNS depressants, anticoagulants (SNRI) or other drugs. May increase risk of falls, or cardiac dysrhythmias.

TCAs reduce intensity of multiple nerve pain types and may improve sleep. 

Heart rate and blood pressure drops may add to the risk of falls. Dry mouth, constipation, confusion, or other anticholinergic side effects.

Avoid in persons with syncope (fainting), heart failure, other anticholinergic or serotonergic drugs. Nortriptyline preferred over amitriptyline.  Monitor vital signs, and for changes in mood, sleep, vision, anticholinergic side effects or suicidality. Collaborate with prescribers of medications for mental health disorders.

SNRIs similarly work for nerve (and possibly other) pain types

May elevate liver enzymes and risk of drug interactions.

Monitor as above and for signs of serotonin syndrome. May increase the risk of hyponatremia and raise INR in patients taking coumadin. Periodic check of liver enzymes.


Sedation is dose-limiting initially, so titrating to a therapeutic dose may take weeks. Start with bedtime dose then add daytime dose(s) as tolerated. Effect on pain seen within 2 weeks at therapeutic dose. The character of pain may change before intensity. Avoid other sedatives (including alcohol).


Commonly used examples:

  • Gabapentinoids (gabapentin, pregabalin)
  • Other Anticonvulsants (carbamazepine, oxcarbazepine, topiramate, etc.)

Adjust dose or avoid with renal dysfunction.

Gabapentinoids often help with neuropathic or widespread pain. May reduce the dose or need for opioids (opioid-sparing)

Sedation, incoordination poor concentration and edema limits dose tolerance.  Reduce dose with renal impairment.

Low starting dose limits side effects. A scheduled regimen is better than prn. Pregabalin may be better tolerated and more effective. Monitor sedation, edema, balance; and for changes in vision, mood or cognition.  Monitor for misuse.

Other anticonvulsants (e.g. carbamazepine, lamotrigine, phenytoin, and topiramate)

 reduce nerve excitability and

spontaneous firing that may cause pain after nerve injury or sensitivity

May elevate liver enzymes and risk of drug interactions, serious rashes or blood anomalies.

As above and close monitoring for drug interactions. Blood tests for possible side effects is warranted.

Report personality changes like apathy or social withdrawal, changes in mood (anxiety), impulsive, socially inappropriate behaviors or hallucinations.

*Physical dependence may occur, do consult prescriber before regimen change, stopping medicine or with multiple missed doses.


Treatment Name and Description




Muscle relaxants or antispasmodics*

Muscle relaxants comprise a heterogeneous group of medicines (with different mechanisms of action) that should generally be avoided in older adults.


Commonly used examples:

  • Benzodiazepine and related sedatives
  • Carisoprodol, orphenadrine,
  • Baclofen
  • Tizanidine

Check for drug-specific interactions and contraindications.

Effectively relax skeletal muscles in different ways to treat muscular pain and spasms. Even peripherally acting relaxants have undesirable central effects with repeated use. 

Sleepiness and risk of falls or injury, drug dependence and serious withdrawal syndrome. Carisoprodol is converted in the body to a drug with abuse potential. Risk of developing/ worsening sleep apnea.

Keep accurate records to avoid taking too many or too few of these medicines. Many have withdrawal syndromes with missed doses or when stopped so get medical advice if not using exactly as prescribed.  Monitor for effect on pain, sedation, fall risk, cognition, and non-medical use.

Baclofen has specific actions making it more effective against spasms. Intrathecal baclofen is more effective and better tolerated than the oral route for severe neurogenic spasticity (e.g., multiple sclerosis, cerebral palsy, and traumatic spine/brain injury)

Sleepiness and greater risk of falls or injury. Physical dependence and a serious withdrawal syndrome may be more than with other muscle relaxants.

Keep accurate records as above and get medical advice before changing the dose or schedule. Avoid activities that may result in injury.

Tizanidine is a short-acting drug that slows the heart, opens blood vessels and can reduce painful muscle tension or spasm. Can be effective certain headaches, nerve or muscular pain types.

Sedation and low blood pressure raise the risk of falls. Abruptly stopping or lowering the dose can cause heart and high blood pressure problems.

Keep accurate records and take precautions, as for other muscle relaxants, to prevent risk of falls or injury. Get medical advice before changing the dose of schedule.

*Physical dependence may occur, do consult prescriber before regimen change, stopping medicine or with multiple missed doses.


Treatment Name and Description





Opioids relieve strong pain by exerting an effect on multiple pre- and post-synaptic ion channels (transmission), activate inhibitory systems or block the production and release of excitatory amino acids (modulation) and alter the mental (perception) effects of pain. With ongoing use, the desired effects wane (tolerance) and many develop new physical and psychosocial problems, including a paradoxical increase in pain sensitivity.

Commonly used examples:

  • Natural and semisynthetic Mu opioid receptor agonists (morphine, hydrocodone, oxycodone, hydromorphone)
  • Synthetic Mu opioid receptor agonists (fentanyl, methadone, buprenorphine)
  • Dual action opioids (tramadol, tapentadol)
  • Mixed agonist-antagonist opioids (pentazocine, butorphanol, nalbuphine)

 Check specific medications for possible interactions with drugs or comorbidities. If allergic signs develop (e.g. hives, itching), synthetic options (e.g., tramadol, buprenorphine) may be better tolerated.

Address untreated substance use disorder, psychiatric illness, or sleep apnea before initiating opioids, if possible, with vigilant monitoring of patients with these comorbid conditions. Risk of myocardial infarction and hormonal imbalance may increase with sustained use.


Opioid agonists improve severe acute pain, functioning and possibly sleep quality. Higher doses do not significantly lower (and may increase) pain. Effects wane with time, limiting their use with persistent pain. Synthetic opioids may have less nausea, itchiness, and rashes if mild allergy symptoms present. Synthetic opioids are preferred in the setting of kidney disease.

Risk of falls/injury, fractures, confusion, dependency and withdrawal syndrome. Addiction and fatal overdoses uncommon when taken as directed but risk increases with other sedating drugs. Meperidine not used because of limited oral effect, neurotoxicity, seizures, and delirium.

Monitor vital signs, pain, sedation, sleep, mood and for nonmedical use. Bowel regimen needed if more than sporadic use. Interacts with other sedating drugs (e.g., benzodiazepines, gabapentinoids and alcohol). Take exactly as prescribed. Store in secure (preferably locked) place, dispose as directed when no longer using. Avoid activities that may result in fall or injury, especially the first weeks of therapy. Monitor for neurocognitive, behavioral and respiratory changes. Educate to report and respond to signs of overdose or withdrawal.

Dual action opioids are less potent and preferred for moderate-severe pain. Less risk of physical dependance or withdrawal. May be preferred for otherwise healthy older adults.

Risk of serotonin syndrome, drug interactions, fractures hypoglycemia, cardiovascular events, and seizures may be increased.

Same concerns as other opioids. Inform the prescriber of all medications taken. Interactions occur with antidepressants, muscle relaxants and other sedating drugs (including alcohol). Dose or frequency of use is often reduced with kidney failure.

Mixed agonist-antagonists produce analgesia by binding to kappa while blocking mu receptor effects. Good for moderate-severe pain. May have less risk of breathing problems and legal restrictions. Buprenorphine (partial mu agonist, weak kappa antagonist) is available in a once-a-week patch.

May precipitate withdrawal symptoms in opioid-dependent persons. Confusion or hallucinations can occur in older adults and those with kidney problems.

Same concerns as other opioids. Inform the prescriber of all medications taken. Other opioids may need to be weaned before starting; or therapy may begin with “micro-dosing.” Keep accurate records to follow instructions as directed.

*Physical dependence may occur, do consult prescriber before regimen change, stopping medicine or with multiple missed doses.


Treatment Name and Description




Epidural Steroid Injection

Epidural steroids are the most common interventional approach for low back pain and are indicated for radicular pain due to lumbar disc herniation or stenosis.

Can relieve painful nerve compression by reducing swelling and inflammation with fewer risks than surgery.

Questionable benefit without clear evidence of nerve compression. Risk of serious infection. Neck injections have greater risk of bleeding or emboli. 

Consider second opinion to discuss individualized benefits and risks. Avoid unnecessary sedation during the procedure. Limit to a few per year. Local Anesthetic provides initial effect, followed by steroid effect.  Monitor for drug-specific side effects.

Intraarticular (Joint) Injection

Corticosteroids (steroids), local anesthetics, hyaluronic acid, or Botox are injected directly into a painful joint.

Steroids may directly reduce inflammation that causes pain. More targeted effects than oral steroids, while limiting systemic effects. May be combined with hyaluronic acid to prolong effects.

Small risk of bleeding or infection in joint. Time-limited effect. Local anesthetic (if used) may cause joint damage. May affect blood glucose in diabetic patients.

Avoid NSAID use when steroid is used. Primarily used for time-limited benefit (e.g., go to a wedding, or vacation). Report to professional if condition worsens during first 1-2 weeks after procedure.  

Vertebral Augmentation

Bone cement is injected into the vertebral column (spine) to stabilize/repair a painful vertebral compression fracture. (vertebroplasty, kyphoplasty)

Percutaneous vertebroplasty can reduce pain and improve function yielding modest benefits after symptomatic vertebral fractures but may not be rated as significantly better.

Serious side effects include spinal infection, cord compression, thecal sac injury and breathing difficulties.

Consider only in select cases where likely benefits outweigh potential harm. Consider a second opinion. Risks of anesthesia, emboli and cement leakage should be considered.


Nerve deadening procedure uses heat (e.g. radiofrequency) or cold (cryoablation) temperatures to damage pain-signaling nerves.

Improves pain and functioning for a limited number of conditions (e.g., chronic back, hip, knee pain). Less invasive than surgery and can lower use of pain medications. 

Effects may wane after several months. Risk of procedural discomfort, infection, bleeding. Serious harm has not been reported.

Only used in selected cases after other treatment failures. Factors influencing risk-benefit decisions include other diseases, drugs, disability, falls risk, and cognitive function, favor benefits over risks.

Implanted Nerve Stimulators

An implanted device that sends low levels of electricity directly to a peripheral, regional or central nerve tissue to disrupt pain-signaling nerve patterns, altering its transmission, modulation and perception.

Technology is rapidly improving with less invasive, more effective, and fewer undesired effects. Best for back, leg and phantom pain.

Risks of bleeding, infection, nerve injury and risks of surgery. Some dislike the numbing sensation. Repeat surgery needed by many in a few years.

Requires highly skilled surgeon and an experienced support team familiar with the technology. Long-term commitment by patient and caregivers to follow directions and keep accurate logs. Cost and access are prohibitive for many.

© Paul Arnstein PhD, RN, FAAN and Marcia Y. Shade PhD, RN 2023

Last Revised March 2023

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