Chronic Pain Syndrome Medication

  • Author: Manish K Singh, MD; Chief Editor: Stephen Kishner, MD, MHA  more...
Updated: May 13, 2016

Medication Summary

Pharmacotherapy for chronic pain syndrome (CPS) consists of symptomatic abortive therapy (to stop or reduce the severity of the acute exacerbations) and long-term therapy for chronic pain. Initially, pain may respond to simple over-the-counter analgesics, such as paracetamol, ibuprofen, aspirin, or naproxen. If treatment is unsatisfactory, the addition of other modalities or the use of prescription drugs is recommended. If possible, avoid barbiturate or opiate agonists. Also, discourage long-term and excessive use of all symptomatic analgesics because of the risk of dependence and abuse.

In a longitudinal outcomes trial, researchers investigated 62 patients with CPS who were at low or high risk for opioid abuse. Researchers explored whether these patients had cravings for their medications, what influenced their cravings, and if a connection existed between craving and medication compliance. Patients noted their cravings at monthly clinic visits and daily during a 14-day period. Both the low- and high-risk groups regularly craved their medication, which was linked to urge, preoccupation, and mood. Focusing on cravings may help correct misuse and better assist with prescription opioid compliance.[26]

Tizanidine may improve the inhibitory function in the central nervous system (CNS) and can provide pain relief. Amitriptyline (Elavil) and nortriptyline (Pamelor) are the tricyclic antidepressants (TCAs) most frequently used to treat chronic pain. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft), as well as the selective serotonin/norepinephrine reuptake inhibitor (SNRI) duloxetine (Cymbalta), are commonly prescribed by many physicians. Other antidepressants, such as doxepin, desipramine protriptyline, and buspirone, also can be used.

A French study found evidence that botulinum toxin type A (BoNT-A) has direct analgesic effects when administered to patients with chronic neuropathic pain (performing actions that are independent of its effect on muscle tone).[27] Consequently, the study's authors suggested that BoNT-A may have "novel indications" in analgesia.

Kroenke et al found that a combination of pharmacologic and behavioral intervention were more effective than conventional therapy in the treatment of patients suffering from depression and chronic pain.[2] Patients (n=250) with low back, hip, or knee pain for 3 months or longer who also had moderate depression were randomly assigned to the combination therapy or usual care. Combination therapy consisted of optimized antidepressant therapy (12wk), followed by intervention for pain in a self-management phase (12wk), and a continuation phase (6 mo).

Depression improved in 37.4% of the combination therapy group (ie, 50% or greater reduction in depression), but in only 16.5% of the usual-care group (16.5%). Pain severity was reduced by 30% or more in 41.5% of the combination group, compared with 17.3% of the usual-care group.

A study by Gianni et al looked at the buprenorphine transdermal delivery system (BTDS) for its effect on chronic, noncancer pain. While the specific aim of this study was to examine cognitive and functional scores in an elderly population treated with the BTDS, a secondary finding related to its use was the effective analgesic activity and safety of BTDS in elderly patients. There was an improvement in mood and a partial resumption of activities, with no influence on cognitive and behavioral ability.[28]

A 2011 study determined that predictive factors for switching to higher-dose transdermal fentanyl in patients with cancer pain who were previously taking either oral morphine or oxycodone were breast cancer, total protein value, alanine aminotransferase value, older age, and male sex.[29]


Antidepressants, Other

Class Summary

These agents increase the synaptic concentration of serotonin and/or norepinephrine in the CNS by inhibiting their reuptake by the presynaptic neuronal membrane.



Amitriptyline is an analgesic for certain chronic and neuropathic pain.

Nortriptyline (Pamelor)


Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS. Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its action.

Duloxetine (Cymbalta)


Duloxetine is indicated for diabetic peripheral neuropathic pain. It is a potent inhibitor of neuronal serotonin and norepinephrine reuptake.

Venlafaxine (Effexor, Effexor XR)


Venlafaxine inhibits neuronal serotonin and norepinephrine reuptake. In addition, it causes beta-receptor down-regulation. Venlafaxine may decrease neuropathic pain and help with sleep and other mood disorders (depression or depressive symptoms).

Fluoxetine (Prozac)


Fluoxetine is an atypical non ̶ tricyclic antidepressant (non-TCA) with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider this drug as an alternative to TCAs.

Sertraline (Zoloft)


Sertraline is an atypical non-TCA with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider it as an alternative to TCAs.

Paroxetine (Paxil, Pexeva)


Paroxetine is an atypical non-TCA with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider it as an alternative to TCAs.



Class Summary

Certain antiepileptic drugs (eg, the gamma-aminobutyric acid [GABA] analogue gabapentin and pregabalin [Lyrica]) have proven helpful in some cases of neuropathic pain.[10] For example, a randomized, double-blind, placebo-controlled study reported that twice-daily doses of gastric-retentive, extended-release gabapentin (gabapentin ER) provided safe and effective treatment for postherpetic neuralgia; nonplacebo patients in the study received 1800 mg of gabapentin per day.[11]

Pregabalin also demonstrated pain relief in diabetic peripheral neuropathy and postherpetic neuralgia. It may provide benefit in other neuropathic pain as well.[30]

A Cochrane Database of Systematic Reviews article that looked at 29 studies with a total of 3571 participants with chronic pain conditions concluded that gabapentin provided pain relief in about 30% of patients. Adverse events, although frequent, were mostly tolerable; they included dizziness, somnolence, peripheral edema, and gait disturbance.[31]

Other anticonvulsant agents (eg, clonazepam, topiramate, lamotrigine, zonisamide, tiagabine) also have been tried in chronic pain syndrome (CPS).

Gabapentin (Neurontin)


Gabapentin has anticonvulsant properties and antineuralgic effects; however, its exact mechanism of action is unknown. It is structurally related to GABA but does not interact with GABA receptors.

Pregabalin (Lyrica)


Pregabalin is a structural derivative of GABA; its mechanism of action unknown. Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit), and in vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. The US Food and Drug Administration (FDA) approved it for the treatment of neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.



Class Summary

Analgesics are commonly used for many pain syndromes. Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained traumatic injuries.

Oxycodone (OxyContin, Roxicodone)


Long-acting opioids may be used in patients with CPS. Start with a small dose and, if appropriate, gradually increase it.

Fentanyl (Duragesic, Fentora, Onsolis, Actiq)


Fentanyl is a potent narcotic analgesic with a much shorter half-life than morphine sulfate. It is the drug of choice for conscious-sedation analgesia. Fentanyl is ideal for analgesic action of short duration during anesthesia and during the immediate postoperative period. It is an excellent choice for pain management and sedation of short duration (30-60min).

Fentanyl is easy to titrate and is easily and quickly reversed by naloxone. When the transdermal dosage form is used, most patients achieve pain control with 72-hour dosing intervals; however, some patients require dosing intervals of 48 hours.

Acetaminophen (Tylenol, FeverAll, Aspirin Free Anacin)


Acetaminophen is the drug of choice for the treatment of pain in patients with documented hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), with upper GI disease, who are pregnant, or who are taking oral anticoagulants.


Nonsteroidal Anti-Inflammatory Drugs

Class Summary

NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Ibuprofen (Motrin, Advil, Addaprin, Caldolor)


Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen sodium (Anaprox, Naprelan, Naprosyn, Anaprox)


This agent is used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclo-oxygenase, which results in a decrease in prostaglandin synthesis.

Diclofenac (Voltaren, Cataflam XR, Zipsor, Cambia)


Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.

Indomethacin (Indocin)


Indomethacin is thought to be the most effective NSAID for the treatment of ankylosing spondylitis, although no scientific evidence supports this claim. It is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.



Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.

Contributor Information and Disclosures

Manish K Singh, MD Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience

Manish K Singh, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Headache Society, American Association of Physicians of Indian Origin, American Medical Association, American Society of Regional Anesthesia and Pain Medicine

Disclosure: Nothing to disclose.


Jashvant Patel, MBBS, MS, MD 

Jashvant Patel, MBBS, MS, MD is a member of the following medical societies: Alberta Medical Association, American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Society of Regional Anesthesia and Pain Medicine, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Rollin McCulloch Gallagher, MD, MPH Clinical Professor, Departments of Psychiatry and Anesthesiology, Director for Health Policy and Primary Care, Penn Pain Medicine, University of Pennsylvania School of Medicine; National Program Director for Pain Management, Veterans Health Administration; Editor-in-Chief, PAIN MEDICINE

Rollin McCulloch Gallagher, MD, MPH is a member of the following medical societies: Academy of Psychosomatic Medicine, American Academy of Pain Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital

Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.


Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine

Richard Salcido, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Physician Executives, American Medical Association, and American Paraplegia Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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