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Chronic Pain

Editor: Till Conermann Updated: 5/6/2024 12:48:49 AM


Over one-quarter of people in the United States (US) suffer from chronic pain—one of the most prevalent issues encountered in outpatient medical settings.[1] However, inadequate management of chronic pain and the subsequent reliance on opioids contribute significantly to morbidity and mortality. Most patient visits in outpatient clinics are prompted by pain-related concerns, with over half seeking relief from their primary care provider. Hence, primary care providers must comprehensively understand chronic pain management. The US spends well over 100 billion dollars annually on healthcare expenses associated with pain management and opioid use disorders.[2] This surpasses the combined expenses of cancer, diabetes, and heart disease.[3][4]

Managing a patient's chronic pain can significantly impact their quality of life. Chronic pain, defined as any pain persisting beyond 3 months, originates from various sources. Effective pain management often involves a combination of pharmacological treatments and nonpharmacological interventions. Research results indicate that multimodal combination therapy yields a more significant reduction in pain than relying solely on single treatments. Escalating pharmacological therapy is typically approached in a stepwise manner. Comorbid depression and anxiety frequently accompany chronic pain yet often go undiagnosed and untreated. Additionally, individuals with chronic pain face an elevated risk of suicide. The pervasive nature of chronic pain can detrimentally affect every aspect of a patient's life, potentially resulting in long-term disability and adverse outcomes. Consequently, diagnosing and appropriately managing chronic pain is a critical skill for healthcare professionals to cultivate.


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Most patients with chronic pain report experiencing multiple types of pain simultaneously.[5] For instance, an individual with chronic back pain might also contend with fibromyalgia. Moreover, a considerable proportion of patients with chronic pain also suffer from major depressive and generalized anxiety disorder, with over 67% experiencing a comorbid psychiatric disorder.[6][7]

Pain manifests in various categories and types, encompassing neuropathic, nociceptive, musculoskeletal, inflammatory, psychogenic, and mechanical forms. The following are some examples of each category:

  • Neuropathic pain: Divided into 2 groups
    • Peripheral neuropathic pain: Postherpetic neuralgia and diabetic neuropathy
    • Central neuropathic pain: Cerebral vascular accident sequella
  • Nociceptive pain: 
    • Pain due to actual tissue injuries such as burns, contusions, sprains as well as surgical pain
  • Musculoskeletal pain
    • Back pain, including radicular pain, to the appropriate dermatome
    • Myofascial pain
  • Inflammatory pain
    • Autoimmune disorders (rheumatoid arthritis, fibromyalgia, and gout)
    • Infection and cancer pain 
  • Psychogenic pain
    • Pain caused by psychological factors, such as headaches or abdominal pain caused by emotional, psychological, or behavioral factors
  • Mechanical pain 
    • Expanding malignancy, benign tumors, advanced ascites, fractures, and retained hardware pain


Over 100 million individuals in the US meet the criteria for chronic pain syndrome, with more than 20 million enduring severe, incapacitating chronic pain.[1] Among patients with chronic pain, chronic regional pain affects 11.1%, chronic back pain accounts for 10.1%, leg and foot pain affects 7.1%, arm and hand pain affects 4.1%, and headache affects 3.5%. Additionally, 3.6% of patients with chronic pain experience widespread pain.[6] 

Older patients receive up to 25% fewer pain medications than the general population.[8] Chronic pain is also associated with metabolic alterations and cognitive disorders among affected individuals.[8][9] Studies indicate that the lifetime prevalence of suicide attempts among patients with chronic pain ranges from 5% to 14%, with approximately 20% experiencing suicidal ideation.[10] Among patients with chronic pain who died by suicide, 53.6% succumbed to firearm-related injuries, while 16.2% died from an opioid overdose.[11][12][13]


Due to the diverse pathology underlying the cause of pain, no single physiological finding can encompass all the various mechanisms that produce symptoms. However, it is understood that regardless of the type of pain, the resulting impact is likely similar.[14] Moreover, the complexity of pain perception and its multifaceted nature shows the importance of a comprehensive approach to pain management.

History and Physical

A thorough medical history is an initial step in diagnosing, differentiating, and evaluating patients with chronic pain. The history should include crucial details such as the onset date, pain description (eg, burning, throbbing, radicular, superficial, or deep), potential injury mechanisms, pain location, and severity. Additionally, identifying factors that alleviate or exacerbate the pain is essential. Understanding whether the pain is constant or intermittent (breakthrough pain) or a mix of both aids in determining appropriate treatment options.

A verbal numeric rating scale or a pain intensity scale ranging from 0-10 is standard for assessing pain severity. Furthermore, it is essential to determine associated symptoms like muscle spasms, skin temperature changes, restricted range of motion, morning stiffness, weakness, muscle strength alterations, sensation changes, and skin, hair, or nail abnormalities.[15]

In addition to assessing the patient's symptoms, it is helpful to explore how chronic pain impacts their day-to-day functioning and quality of life. This entails discussing the effect of pain on activities of daily living and overall functionality. Understanding how pain influences relationships, hobbies, and emotional well-being is vital. Questions about depression, sleep quality, exercise tolerance, work productivity, and the ability to perform basic tasks like toileting, dressing, bathing, walking, or eating without limitations are pertinent to a comprehensive understanding of the patient's condition.

Following the comprehensive history, the physical examination should include detailed assessments of strength, range of motion, and flexibility. The physical examination must corroborate the details reported in the history and support the patient's pain complaints. Auscultation of the lungs and heart and palpation of the abdomen allow the clinician to observe the patient's movements as they transition onto and off the examination table.[16] Observation of the patient is crucial for confirming the reported complaints---allowing the examiner to differentiate between the patient's perception of pain and any fear or anticipation of pain that can significantly influence the treatment plan.[16]

Additionally, a thorough neurological examination should be conducted during the physical assessment. There is benefit in closely examining the area of pain, paying attention to any skin changes, temperature variations between extremities, trophic changes resulting from chronic exposure to heat or cold compresses, and any excoriations from chronic picking. Furthermore, observing for hair loss on the scalp and extremities can provide valuable insights into the patient's condition.[17]

Older adults constitute a specific demographic frequently affected by chronic pain, yet self-reporting of pain can be challenging in this population. Accurate self-reporting is crucial for identifying and effectively treating pain; however, difficulties in describing and communicating pain often lead to undertreatment. Moreover, older patients may express their pain differently than the general population, complicating the diagnosis.[8][18] Rather than explicitly labeling it pain, an older individual might only describe soreness or discomfort.[19][20][21]


The Brief Pain Inventory (BPI) is a valuable tool for evaluating patients' perceptions of pain and its impact on their daily lives.[22][23] Additionally, the McGill Pain Questionnaire (SF-MPQ-2) includes a pain location drawing, a questionnaire regarding previous pain medication use, and experiences with pain history.[24] Neuropathic pain is assessable using the Neuropathic Pain Scale to monitor responses to therapy.

Standard blood work and imaging are not recommended for routine evaluation of chronic pain. However, clinicians may order these tests when specific underlying causes are suspected. Laboratory studies can be requested on a case-by-case basis, including baseline studies to evaluate liver function when certain medications with potential hepatic side effects are prescribed.

Psychiatric disorders can exacerbate pain signaling, intensifying pain symptoms.[25] Furthermore, comorbid psychiatric conditions, such as major depressive disorder, can significantly delay the diagnosis of pain disorders.[7][26] Major depressive disorder and generalized anxiety disorders are the most prevalent comorbidities associated with chronic pain.

Patients with underlying pain and comorbid psychiatric disorders receive approximately twice as many opioid prescriptions annually compared to those without such comorbidity.[19] For instance, individuals with depression commonly experience fatigue, sleep disturbances, decreased appetite, and reduced activity levels, all of which can exacerbate pain symptoms over time. Patients with chronic pain face an elevated risk of suicide and suicidal ideation.[10][11]

Screening for depression is advised for patients experiencing chronic pain. The Minnesota Multiphasic Personality Inventory-II (MMPI-2) and Beck Depression Scale are the primary assessment tools utilized for this purpose. Among these, the MMPI-2 is more commonly used for patients with chronic pain.[27][28][29][30]

Treatment / Management

When debilitating pain persists despite therapeutic interventions, referral to a pain management specialist is warranted. The pain may be widespread, necessitating multimodal treatment approaches or adjustments in medication dosages to achieve adequate pain control. In some cases, invasive procedures designed to control refractory pain may be recommended.

It is essential to address both the pain itself and any comorbid conditions, especially psychiatric disorders, to develop a comprehensive treatment plan. Research indicates that addressing both pain and psychiatric disorders leads to more significant reductions in pain severity and associated symptoms.[31][32] Moreover, chronic pain can exacerbate concurrent depression, highlighting the importance of pain management in improving responses to depression.[33][34] Patients have access to various pharmacological, adjunct, nonpharmacological, and interventional treatments tailored to their needs for managing chronic, severe, and refractory pain.(A1)

The array of pharmacological options for chronic pain management is extensive. Nonopioid analgesics such as nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, and aspirin are commonly used. Additionally, medications such as tramadol, opioids, and antiepileptic drugs like gabapentin or pregabalin can be effective. Furthermore, antidepressants such as tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors (SNRIs), topical analgesics, muscle relaxers, N-methyl-d-aspartate (NMDA) receptor antagonists, and alpha 2 adrenergic agonists are also possible pharmacological therapies for managing chronic pain.[32](A1)

Treatment responses can vary among individuals, but typically, a stepwise approach is adopted to minimize the duration and dosage of opioid analgesics. However, there is no singular approach to pain treatment, underscoring the significance of conducting a comprehensive initial work-up.[35]

Chronic musculoskeletal pain, characterized as nociceptive pain, is typically managed in a stepwise manner, often incorporating a combination of nonopioid analgesics, opioids, and nonpharmacological therapies. Acetaminophen and NSAIDs serve as first-line therapies due to their efficacy in conditions like osteoarthritis and chronic back pain.[36][37][38][39] However, NSAIDs are relatively contraindicated for individuals with a history of heart disease, myocardial infarction, renal disease, or those on anticoagulation or with a history of ulcers.[40][41] There is limited evidence to suggest one NSAID is superior to another; therefore, trying different agents is recommended before considering opioid analgesics.[42] If adequate pain relief is not achieved with acetaminophen or NSAIDs, opioid analgesics may be considered. (A1)

Opioids are considered a second-line option for pain management; however, they may be warranted in cases of severe persistent pain or neuropathic pain secondary to malignancy.[43] The evidence regarding the use of opioids in neuropathic pain is mixed, but they are often utilized for short-term and intermediate pain relief in this context.[44][45] When initiating opioid therapy for chronic musculoskeletal pain, extreme caution is advised due to the significant side effects associated with opioids, including opioid-induced hyperalgesia, constipation, dependence, and sedation.[46] Additionally, for chronic musculoskeletal pain, opioids are not found to be superior to nonopioid analgesics.[47][48](A1)

The administration of opioid analgesics is recommended when alternative pain medications have proven ineffective or contraindicated and when pain significantly impacts the patient's quality of life, with the potential benefits outweighing the short and long-term effects of opioid therapy. However, patients must make an informed decision before initiating opioid treatment, following a thorough discussion of the associated risks, benefits, and available alternatives.[47][49][50] (A1)

Notably, patients taking opioids at doses exceeding 100 morphine milligram equivalents per day are at significantly increased risk of side effects, with respiratory compromise becoming more prevalent as dosages escalate. Therefore, patients with chronic pain may benefit from a structured therapy program aimed at tapering them off high-opioid regimens to safer levels.[51][52] Long-acting opioids should be reserved for cases of disabling pain that severely impairs quality of life, with short-acting opioids preferred otherwise.[53][54]

There is an estimated 78% risk of experiencing adverse reactions to opioids, including constipation or nausea, with a 7.5% risk of severe adverse reactions, ranging from immunosuppression to respiratory depression.[55] For patients with chronic pain who meet the criteria for opioid use disorder, buprenorphine should be considered as an option for managing their pain. Buprenorphine is a preferable alternative, especially for individuals with very high daily morphine equivalents who have not achieved sufficient analgesia with other treatments.[56][57][58](B2)

Different types of pain warrant distinct treatment approaches. For example, chronic musculoskeletal back pain would be managed differently from severe diabetic neuropathy. Neuropathic pain often requires a combination of multiple pharmacological therapies, as less than 50% of patients achieve adequate pain relief with a single agent.[59] Adjunctive topical therapies, such as lidocaine or capsaicin cream, can also be beneficial in managing neuropathic pain.[60][61][62](A1)

The initial pharmacological approach to treating neuropathic pain often involves gabapentin or pregabalin, both of which are calcium channel alpha 2-delta ligands. The medications are indicated for conditions like postherpetic neuralgia, diabetic neuropathy, and mixed neuropathy.[63] While there is limited evidence supporting the use of other antiepileptic medications to treat chronic pain, where many of these, such as lamotrigine, have a more significant side effect profile. The exception is carbamazepine in the treatment of trigeminal neuralgia and other forms of chronic neuropathic pain.[64][65](A1)

Alternatively, antidepressants such as dual reuptake inhibitors of serotonin and norepinephrine (SNRI) or tricyclic antidepressants (TCA) represent another treatment option. Antidepressants are beneficial in managing neuropathic pain, central pain syndromes, and chronic musculoskeletal pain. In the case of neuropathic pain, antidepressants have demonstrated a 50% reduction in pain intensity. This substantial reduction is noteworthy, especially considering that the average pain reduction achieved by various pain treatments is around 30%.[66][67][68](A1)

The SNRI duloxetine is effective in treating chronic pain, osteoarthritis, and fibromyalgia.[69] Furthermore, duloxetine demonstrates comparable efficacy in treating comorbid depression when compared to other antidepressants.[66][70] Venlafaxine is another effective option for treating neuropathic pain.[71] TCAs, such as nortriptyline, can also be utilized for pain management. However, it is important to note that TCAs may require  6-8 weeks to achieve their desired therapeutic effect.[43](A1)

Adjunctive topical agents, such as topical lidocaine, are beneficial for managing neuropathic pain and allodynia, as observed in postherpetic neuralgia.[72][73] While topical NSAIDs have demonstrated efficacy in improving acute musculoskeletal pain, such as strains, their effectiveness in chronic pain is limited. However, they are more effective than controls in treating pain associated with knee osteoarthritis.[74][75] (A1)

Additionally, topical capsaicin cream is an option for chronic neuropathic or musculoskeletal pain that is unresponsive to other treatments.[76] Botulinum toxin has also demonstrated effectiveness in the treatment of postherpetic neuralgia.[77] Cannabis use is an area of interest in pain research, with some evidence suggesting that medical marijuana can effectively treat neuropathic pain, although evidence for treating other types of chronic pain remains limited.[78](A1)

The array of nonpharmacological therapies for chronic pain is extensive. These options include heat and cold therapy, cognitive behavioral therapy, relaxation therapy, biofeedback, group counseling, ultrasound stimulation, acupuncture, aerobic exercise, chiropractic, physical therapy, osteopathic manipulative medicine, occupational therapy, and transcutaneous electrical nerve stimulation (TENS) units. In addition to these therapies, interventional techniques are crucial in chronic pain treatment. These techniques include spinal cord stimulation, epidural steroid injections, radiofrequency nerve ablations, botulinum toxin injections, nerve blocks, trigger point injections, and intrathecal pain pumps.

The efficacy of TENS units has shown variability, and their role in chronic pain management remains inconclusive.[79] Deep brain stimulation is reserved for post-stroke and facial pain, as well as severe, intractable pain refractory to other treatments.[80] While evidence for interventional approaches to pain management is limited, implantable intrathecal delivery systems can be considered for patients with refractory pain who have exhausted all other options.(A1)

Spinal cord stimulators represent a viable option for patients with chronic pain who have not responded to conservative treatments. While they are most frequently implanted following failed back surgery, they can be considered for various other causes of chronic pain, including complex regional pain syndrome, painful peripheral vascular disease, intractable angina, painful diabetic neuropathy, and visceral abdominal and perineal pain.[81][82][83][84][85] Research indicates that spinal cord stimulators can lead to a significant 50% reduction in pain compared to continued medical therapy.[86][87][88](A1)

Differential Diagnosis

Pain is a symptom, not a diagnosis. Therefore, developing a differential diagnosis for a patient's chronic pain involves assessing their underlying etiologies. Determining the underlying injury or disease process responsible for the pain is essential because effective treatment hinges on understanding the etiology. For instance, distinguishing between peripheral and central neuropathic pain is necessary as it dictates the most effective treatment modality.

Similarly, when a patient presents with severe knee pain, it is essential to differentiate between conditions like severe osteoarthritis and rheumatoid arthritis. This determination influences whether treatments such as injections or knee replacement would be beneficial. Conversely, if the knee pain were due to conditions like rheumatoid arthritis, infection, gout, pseudogout, or meniscal injury, different treatments could be more efficacious.

The differential diagnosis for generalized chronic pain encompasses various conditions, including patients who develop allodynia from chronic opioid use, those suffering from major depressive disorder, and other psychiatric disorders like bipolar disorder and schizophrenia. Furthermore, autoimmune diseases such as lupus or psoriatic arthritis, fibromyalgia, and central pain syndromes should be considered in cases involving widespread, generalized chronic pain.

The 4 main categories of pain—neuropathic, musculoskeletal, mechanical, and inflammatory—should guide the diagnostic process. Persistent and undertreated painful conditions can lead to chronic pain, which often becomes a symptom of one or multiple diagnoses and can eventually become a diagnosis itself as it persists and alters the body's neurochemistry. Treating acute and subacute pain promptly is crucial in preventing the development of chronic pain syndromes. 


Current chronic pain treatments can result in an estimated 30% decrease in a patient's pain scores.[35] A thirty percent reduction in a patient's pain can significantly improve patients' function and quality of life.[89] However, the long-term prognosis for patients with chronic pain demonstrates reduced function and quality of life. Improved outcomes are possible in patients with chronic pain improves with the treatment of comorbid psychiatric illness. Chronic pain increases patient morbidity and mortality, as well as increases rates of chronic disease and obesity. Patients with chronic pain are also at a significantly increased risk for suicide compared to the regular population.

Spinal cord stimulation results in inadequate pain relief in about 50% of patients. Tolerance can also occur in up to 20 to 40 percent of patients. The effectiveness of the spinal cord stimulation decreases over time.[90] Similarly, patients who develop chronic pain and are dependent on opioids often build tolerance over time. As the amount of morphine milligram equivalents increases, the patient's morbidity and mortality also increase.

Ultimately, prevention is critical in the treatment of chronic pain. If acute and subacute pain receives appropriate treatment and chronic pain can be avoided, the patient will have limited impacts on their quality of life. 


Chronic pain significantly decreases quality of life and productivity and can lead to lost wages. It worsens chronic diseases and contributes to psychiatric disorders such as depression, anxiety, and substance abuse disorders. Patients with chronic pain face a significantly increased risk of suicide and suicidal ideation.

Many medications commonly used to treat chronic pain carry potential risks, side effects, and possible complications. Acetaminophen is a standard pharmacological therapy for patients with chronic pain, taken either as a single agent or in combination with an opioid. However, hepatotoxicity can occur, especially with doses exceeding 4 grams per day, making it the most common cause of acute liver failure in the US.[91][92] Furthermore, hepatotoxicity can occur at therapeutic doses for patients diagnosed with chronic liver disease.[93]

Frequently used adjunct medications such as gabapentin or pregabalin can cause sedation, swelling, mood changes, confusion, and respiratory depression in older patients who require additional analgesics.[94] These agents require caution in older patients with painful diabetic neuropathy. Moreover, combining gabapentin or pregabalin with opioid analgesics has been shown to increase the rate of patient mortality.[95]

Duloxetine can cause mood changes, headaches, nausea, and other possible side effects and should be avoided in patients with a history of kidney or liver disease. Patients with these conditions should be closely monitored if duloxetine is prescribed.

Feared complications of opioid therapy include addiction, overdose resulting in respiratory compromise, and occasionally, death. However, opioid-induced hyperalgesia is also a significant concern, where patients become more sensitive to painful stimuli while on chronic opioids.[96] The long-term risks and side effects of opioids include constipation, tolerance, dependence, nausea, dyspepsia, arrhythmia (methadone treatment QT prolongation), and opioid-induced endocrine dysfunction, which can result in amenorrhea, impotence, gynecomastia, and decreased energy and libido. Additionally, there appears to be a dose-dependent risk of opioid overdose with increasing daily milligram morphine equivalents.

Complication rates for spinal cord stimulators are high, ranging from 5% up to 40%.[97][98] Most commonly, lead migration occurs, causing inadequate pain relief and requiring revision and anchoring.[99][100] Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra.[101][102] Spinal cord stimulator lead fracture can occur in up to 9% of placements.[103][104] Seromas are also very common and may require surgical incision and drainage.[97][105] The risk of infection following a spinal cord stimulator placement is between 2.5% and 12%.[106][107] Lastly, direct spinal cord trauma could occur. The most significant infectious complication would be a spinal cord abscess. Dural puncture is rare but can cause a post-dural headache in up to 70% of patients.[105][108][109] The most critical adverse event in spinal cord stimulator placement would be a spinal epidural hematoma, which requires immediate neurosurgical decompression. The incidence of a spinal epidural hematoma is 0.71%.[110]

Deterrence and Patient Education

Chronic pain management is most effective when handled by an interprofessional team, which includes a primary care physician and a pain management specialist. A multimodal treatment approach is optimal for achieving better pain control and outcomes while minimizing the need for high-risk treatments such as opioids.

Medication dosages should be gradually increased stepwise and titrated according to the patient's pain level. Patients on chronic opioids should be offered medications for opioid addiction if there are concerns about dependence or misuse. Clinicians can offer interventional procedures to patients with chronic pain who are unresponsive to medications or those who wish to reduce or discontinue chronic opioid treatment.

Management of comorbid depression and anxiety is crucial for reducing chronic pain. The older population may describe pain differently than the average population. Following spinal cord stimulator implantation, patients should have periodic visits with their pain provider to adjust the stimulator's settings for maximum effectiveness. Patients with chronic pain should be closely monitored for severe depression and suicidal ideation. Regular assessment and intervention for mental health issues are essential in ensuring the overall well-being of chronic pain patients with chronic pain.

Pearls and Other Issues

Key facts to keep in mind about chronic pain management include the following:

  • Multimodal approach: Combine pharmacological and nonpharmacological therapies for better pain control.
  • Interprofessional team: Primary care physicians and pain management specialists work together.
  • Medication management:
    • Start with nonopioid analgesics like acetaminophen or NSAIDs.
    • Gradually increase dosages stepwise according to pain.
    • Be cautious of side effects of adjunct medications like gabapentin or pregabalin.
    • Offer opioid addiction medications if misuse is a concern.
  • Interventional procedures: Consider for refractory pain or opioid reduction.
  • Psychological factors: Manage comorbid depression and anxiety.
  • Older patients: Note different pain expressions and special considerations.
  • Monitoring: Regularly assess for severe depression or suicidal ideation.
  • Safety concerns with opioids:
    • Know risks like addiction, overdose, and hyperalgesia.
    • Understand long-term effects like constipation, tolerance, and dependence.

Enhancing Healthcare Team Outcomes

Chronic pain is a complex condition with significant implications for patient's quality of life, requiring a comprehensive and interprofessional approach to management. To ensure patient-centered care, favorable outcomes, patient safety, and effective team performance, healthcare professionals across various disciplines must possess specific skills, adhere to ethical principles, understand their responsibilities, communicate effectively, and coordinate care efficiently.

Healthcare professionals in chronic pain management must possess various skills, including advanced assessment techniques, knowledge of evidence-based treatments, and proficiency in administering multiple therapies. Physicians, advanced practitioners, nurses, pharmacists, and other healthcare providers should continually update their skills through training and education to deliver the best possible care to patients with chronic pain.

A strategic approach to chronic pain management involves early evaluation, conservative treatment when symptoms are mild or moderate, and escalation of therapy as needed. A pharmacist should evaluate pharmacological management regularly to prevent adverse drug interactions. The interprofessional team should develop a cohesive plan that addresses the patient's physical, psychological, and social needs.

Each member of the interprofessional team has specific responsibilities in chronic pain management. Physicians and advanced practitioners are responsible for accurate diagnosis and treatment planning, while nurses monitor patient progress and compliance with the treatment plan. Pharmacists ensure medication safety and reconciliation; other healthcare professionals contribute their expertise as needed.

Effective communication among team members is crucial for providing seamless care to patients with chronic pain. Regular meetings, case conferences, and shared electronic health records facilitate communication and collaboration, ensuring alignment of treatment goals and timely interventions.

Coordinating care across different settings and disciplines is essential to address the multifaceted nature of chronic pain. Patients should have regular follow-up appointments with their primary care provider and specialists as needed. Nursing is crucial in monitoring patient progress, identifying adverse effects, and communicating concerns to the treating physicians.

Additionally, nurses can support patients with chronic pain by providing education on pain management techniques, facilitating access to resources, and advocating for their needs within the healthcare system. Pharmacists can conduct medication therapy management to optimize drug therapy and provide patient education on medication use and side effects.

In summary, by enhancing skills, adopting strategic approaches, upholding ethical principles, fulfilling responsibilities, promoting interprofessional communication, and coordinating care effectively, healthcare professionals can enhance patient-centered care, improve outcomes, ensure patient safety, and optimize team performance in chronic pain management.



Nahin RL. Estimates of pain prevalence and severity in adults: United States, 2012. The journal of pain. 2015 Aug:16(8):769-80. doi: 10.1016/j.jpain.2015.05.002. Epub 2015 May 29     [PubMed PMID: 26028573]


Alford DP, Krebs EE, Chen IA, Nicolaidis C, Bair MJ, Liebschutz J. Update in pain medicine. Journal of general internal medicine. 2010 Nov:25(11):1222-6. doi: 10.1007/s11606-010-1452-4. Epub 2010 Jul 15     [PubMed PMID: 20632120]


Pizzo PA, Clark NM. Alleviating suffering 101--pain relief in the United States. The New England journal of medicine. 2012 Jan 19:366(3):197-9. doi: 10.1056/NEJMp1109084. Epub     [PubMed PMID: 22256802]


Bulls HW, Hamm M, Wasilewski J, Olejniczak D, Bell SG, Liebschutz JM. "To prescribe or not to prescribe, that is the question": Perspectives on opioid prescribing for chronic, cancer-related pain from clinicians who treat pain in survivorship. Cancer. 2024 Apr 3:():. doi: 10.1002/cncr.35299. Epub 2024 Apr 3     [PubMed PMID: 38567685]

Level 3 (low-level) evidence


Hardt J, Jacobsen C, Goldberg J, Nickel R, Buchwald D. Prevalence of chronic pain in a representative sample in the United States. Pain medicine (Malden, Mass.). 2008 Oct:9(7):803-12. doi: 10.1111/j.1526-4637.2008.00425.x. Epub 2008 Mar 11     [PubMed PMID: 18346058]


Annagür BB, Uguz F, Apiliogullari S, Kara I, Gunduz S. Psychiatric disorders and association with quality of sleep and quality of life in patients with chronic pain: a SCID-based study. Pain medicine (Malden, Mass.). 2014 May:15(5):772-81. doi: 10.1111/pme.12390. Epub 2014 Feb 25     [PubMed PMID: 24612225]

Level 2 (mid-level) evidence


Roy BD, Li J, Lally C, Akerman SC, Sullivan MA, Fratantonio J, Flanders WD, Wenten M. Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder. BMC psychiatry. 2024 Apr 2:24(1):244. doi: 10.1186/s12888-024-05676-5. Epub 2024 Apr 2     [PubMed PMID: 38566055]


Feldt KS, Ryden MB, Miles S. Treatment of pain in cognitively impaired compared with cognitively intact older patients with hip-fracture. Journal of the American Geriatrics Society. 1998 Sep:46(9):1079-85     [PubMed PMID: 9736099]


Moriya M, Hu L, Sakatani K, Kitahara M. Estimation of cognitive impairment in chronic pain patients and characteristics of estimated mild cognitive impairment. Frontiers in neurology. 2024:15():1344190. doi: 10.3389/fneur.2024.1344190. Epub 2024 Mar 5     [PubMed PMID: 38523612]


Tang NK, Crane C. Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychological medicine. 2006 May:36(5):575-86     [PubMed PMID: 16420727]


Petrosky E, Harpaz R, Fowler KA, Bohm MK, Helmick CG, Yuan K, Betz CJ. Chronic Pain Among Suicide Decedents, 2003 to 2014: Findings From the National Violent Death Reporting System. Annals of internal medicine. 2018 Oct 2:169(7):448-455. doi: 10.7326/M18-0830. Epub 2018 Sep 11     [PubMed PMID: 30208405]


Balit J, Erlangsen A, Docherty A, Turecki G, Orri M. Association of chronic pain with suicide attempt and death by suicide: a two-sample Mendelian randomization. Molecular psychiatry. 2024 Feb 16:():. doi: 10.1038/s41380-024-02465-0. Epub 2024 Feb 16     [PubMed PMID: 38366113]


Redding A, Kalesnikava VA, Bergmans R, Redding S, Dent K, Mezuk B. Medically unexplained pain and suicidal ideation among US adults. Journal of affective disorders. 2024 Apr 15:351():425-429. doi: 10.1016/j.jad.2024.01.192. Epub 2024 Jan 23     [PubMed PMID: 38272364]


Howlett CA, Stanford T, Berryman C, Karran EL, Bellan V, Coussens S, Miles S, Moseley GL. Investigating self-report and neuropsychological assessments of cognitive flexibility in people with and without persistent pain: An online, cross-sectional, observational study. British journal of pain. 2024 Apr:18(2):176-196. doi: 10.1177/20494637231215260. Epub 2023 Nov 21     [PubMed PMID: 38545498]

Level 2 (mid-level) evidence


Burden AD, Bissonnette R, Anatchkova M, Budhiarso I, Skalicky AM, Liberato ACS, Hu N, Thoma C, Gloede T, Kohlmann T, Lebwohl MG. Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2024 Feb 9:():. doi: 10.1111/jdv.19830. Epub 2024 Feb 9     [PubMed PMID: 38334243]

Level 1 (high-level) evidence


Venturin D, Battimelli A, di Cara G, Poser A. The multidisciplinary team in the management of chronic pain and pain-related fear: an evidence-based approach in a clinical case. Physiotherapy theory and practice. 2024 Mar 29:():1-18. doi: 10.1080/09593985.2024.2336099. Epub 2024 Mar 29     [PubMed PMID: 38551215]

Level 3 (low-level) evidence


Karagounis T, Yan D, Oza V, Kim R. Chronic tongue pain and alopecia. Pediatric dermatology. 2021 Nov:38(6):e58-e60. doi: 10.1111/pde.14797. Epub     [PubMed PMID: 34931369]


AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. Journal of the American Geriatrics Society. 2002 Jun:50(6 Suppl):S205-24     [PubMed PMID: 12067390]


Closs SJ, Briggs M. Patients' verbal descriptions of pain and discomfort following orthopaedic surgery. International journal of nursing studies. 2002 Jul:39(5):563-72     [PubMed PMID: 11996877]


Pickering G, Engelen S, Stupar M, Ganry H, Eerdekens M. Is the Capsaicin 179 mg (8% w/w) Cutaneous Patch an Appropriate Treatment Option for Older Patients with Peripheral Neuropathic Pain? Journal of pain research. 2024:17():1327-1344. doi: 10.2147/JPR.S435809. Epub 2024 Mar 27     [PubMed PMID: 38560405]


Hughes J, Atee M, Chivers P, Hoti K. Comments on Pu et al. (2024) 'Associations between facial expressions and observational pain in residents with dementia and chronic pain'. Journal of advanced nursing. 2024 Apr 1:():. doi: 10.1111/jan.16182. Epub 2024 Apr 1     [PubMed PMID: 38558457]

Level 3 (low-level) evidence


Keller S, Bann CM, Dodd SL, Schein J, Mendoza TR, Cleeland CS. Validity of the brief pain inventory for use in documenting the outcomes of patients with noncancer pain. The Clinical journal of pain. 2004 Sep-Oct:20(5):309-18     [PubMed PMID: 15322437]


Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Annals of the Academy of Medicine, Singapore. 1994 Mar:23(2):129-38     [PubMed PMID: 8080219]


Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009 Jul:144(1-2):35-42. doi: 10.1016/j.pain.2009.02.007. Epub 2009 Apr 7     [PubMed PMID: 19356853]

Level 1 (high-level) evidence


Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science (New York, N.Y.). 2000 Jun 9:288(5472):1769-72     [PubMed PMID: 10846154]

Level 3 (low-level) evidence


Clark L, Jones K, Pennington K. Pain assessment practices with nursing home residents. Western journal of nursing research. 2004 Nov:26(7):733-50     [PubMed PMID: 15466611]


Long CJ. The relationship between surgical outcome and MMPI profiles in chronic pain patients. Journal of clinical psychology. 1981 Oct:37(4):744-9     [PubMed PMID: 6458625]

Level 2 (mid-level) evidence


BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Archives of general psychiatry. 1961 Jun:4():561-71     [PubMed PMID: 13688369]


Wolf EJ, Higgins DM, Zhao X, Hawn SE, Sanborn V, Todd CA, Fein-Schaffer D, Houranieh A, Miller MW. MMPI-2-RF Profiles of Treatment-Seeking Veterans in a VA Pain Clinic and Associations with Markers of Physical Performance. Journal of clinical psychology in medical settings. 2024 Mar:31(1):58-76. doi: 10.1007/s10880-023-09967-z. Epub 2023 Jul 7     [PubMed PMID: 37418093]


Albayrak GS, Saçmacı H, Albayrak L, Bozkurt G, Karaaslan Ö, İnan LE. A cross-sectional study on the personality traits of episodic and chronic migraine patients. Clinical neurology and neurosurgery. 2023 Apr:227():107641. doi: 10.1016/j.clineuro.2023.107641. Epub 2023 Mar 1     [PubMed PMID: 36871391]

Level 2 (mid-level) evidence


Arnow BA, Hunkeler EM, Blasey CM, Lee J, Constantino MJ, Fireman B, Kraemer HC, Dea R, Robinson R, Hayward C. Comorbid depression, chronic pain, and disability in primary care. Psychosomatic medicine. 2006 Mar-Apr:68(2):262-8     [PubMed PMID: 16554392]


de Sousa BM, López-Valverde A, Caramelo F, Rodrigues MJ, López-Valverde N. Use of antidepressants in the treatment of chronic orofacial pain caused by temporomandibular disorders: A randomized controlled clinical trial. Medicina clinica. 2024 Apr 2:():. pii: S0025-7753(24)00128-3. doi: 10.1016/j.medcli.2024.02.002. Epub 2024 Apr 2     [PubMed PMID: 38570297]

Level 1 (high-level) evidence


Fishbain DA, Cole B, Lewis JE, Gao J. Does pain interfere with antidepressant depression treatment response and remission in patients with depression and pain? An evidence-based structured review. Pain medicine (Malden, Mass.). 2014 Sep:15(9):1522-39. doi: 10.1111/pme.12448. Epub 2014 Aug 19     [PubMed PMID: 25139618]

Level 2 (mid-level) evidence


Mokhtari T, Irandoost E, Sheikhbahaei F. Stress, pain, anxiety, and depression in endometriosis-Targeting glial activation and inflammation. International immunopharmacology. 2024 May 10:132():111942. doi: 10.1016/j.intimp.2024.111942. Epub 2024 Apr 2     [PubMed PMID: 38565045]


Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet (London, England). 2011 Jun 25:377(9784):2226-35. doi: 10.1016/S0140-6736(11)60402-9. Epub     [PubMed PMID: 21704872]


Chou R, Qaseem A, Snow V, Casey D, Cross JT Jr, Shekelle P, Owens DK, Clinical Efficacy Assessment Subcommittee of the American College of Physicians, American College of Physicians, American Pain Society Low Back Pain Guidelines Panel. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Annals of internal medicine. 2007 Oct 2:147(7):478-91     [PubMed PMID: 17909209]

Level 3 (low-level) evidence


Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dinçer F, Dziedzic K, Häuselmann HJ, Herrero-Beaumont G, Kaklamanis P, Lohmander S, Maheu E, Martín-Mola E, Pavelka K, Punzi L, Reiter S, Sautner J, Smolen J, Verbruggen G, Zimmermann-Górska I. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Annals of the rheumatic diseases. 2007 Mar:66(3):377-88     [PubMed PMID: 17046965]


Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis and cartilage. 2008 Feb:16(2):137-62. doi: 10.1016/j.joca.2007.12.013. Epub     [PubMed PMID: 18279766]

Level 1 (high-level) evidence


Ide J, Shoaibi A, Wagner K, Weinstein R, Boyle KE, Myers A. Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study. Drugs & aging. 2024 Apr:41(4):357-366. doi: 10.1007/s40266-024-01108-x. Epub 2024 Mar 23     [PubMed PMID: 38520626]


Bjordal JM, Ljunggren AE, Klovning A, Slørdal L. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ (Clinical research ed.). 2004 Dec 4:329(7478):1317     [PubMed PMID: 15561731]

Level 1 (high-level) evidence


Fendrick AM, Greenberg BP. A review of the benefits and risks of nonsteroidal anti-inflammatory drugs in the management of mild-to-moderate osteoarthritis. Osteopathic medicine and primary care. 2009 Jan 6:3():1. doi: 10.1186/1750-4732-3-1. Epub 2009 Jan 6     [PubMed PMID: 19126235]


Rasmussen-Barr E, Held U, Grooten WJA, Roelofs PDDM, Koes BW, van Tulder MW, Wertli MM. Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review. Spine. 2017 Apr 15:42(8):586-594. doi: 10.1097/BRS.0000000000002092. Epub     [PubMed PMID: 28399072]


Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice ASC, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007 Dec 5:132(3):237-251. doi: 10.1016/j.pain.2007.08.033. Epub 2007 Oct 24     [PubMed PMID: 17920770]

Level 3 (low-level) evidence


McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. The Cochrane database of systematic reviews. 2013 Aug 29:2013(8):CD006146. doi: 10.1002/14651858.CD006146.pub2. Epub 2013 Aug 29     [PubMed PMID: 23986501]

Level 1 (high-level) evidence


Coelho DRA, Gersten M, Jimenez AS, Fregni F, Cassano P, Vieira WF. Treating neuropathic pain and comorbid affective disorders: Preclinical and clinical evidence. Pain practice : the official journal of World Institute of Pain. 2024 Apr 4:():. doi: 10.1111/papr.13370. Epub 2024 Apr 4     [PubMed PMID: 38572653]


Von Korff M, Kolodny A, Deyo RA, Chou R. Long-term opioid therapy reconsidered. Annals of internal medicine. 2011 Sep 6:155(5):325-8. doi: 10.7326/0003-4819-155-5-201109060-00011. Epub     [PubMed PMID: 21893626]


Santos J, Alarcão J, Fareleira F, Vaz-Carneiro A, Costa J. Tapentadol for chronic musculoskeletal pain in adults. The Cochrane database of systematic reviews. 2015 May 27:2015(5):CD009923. doi: 10.1002/14651858.CD009923.pub2. Epub 2015 May 27     [PubMed PMID: 26017279]

Level 1 (high-level) evidence


Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Noorbaloochi S. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018 Mar 6:319(9):872-882. doi: 10.1001/jama.2018.0899. Epub     [PubMed PMID: 29509867]

Level 1 (high-level) evidence


Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P, Donovan MI, Fishbain DA, Foley KM, Fudin J, Gilson AM, Kelter A, Mauskop A, O'Connor PG, Passik SD, Pasternak GW, Portenoy RK, Rich BA, Roberts RG, Todd KH, Miaskowski C, American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The journal of pain. 2009 Feb:10(2):113-30. doi: 10.1016/j.jpain.2008.10.008. Epub     [PubMed PMID: 19187889]


Frieden TR, Houry D. Reducing the Risks of Relief--The CDC Opioid-Prescribing Guideline. The New England journal of medicine. 2016 Apr 21:374(16):1501-4. doi: 10.1056/NEJMp1515917. Epub 2016 Mar 15     [PubMed PMID: 26977701]


Dublin S, Walker RL, Shortreed SM, Ludman EJ, Sherman KJ, Hansen RN, Thakral M, Saunders K, Parchman ML, Von Korff M. Impact of initiatives to reduce prescription opioid risks on medically attended injuries in people using chronic opioid therapy. Pharmacoepidemiology and drug safety. 2019 Jan:28(1):90-96. doi: 10.1002/pds.4678. Epub 2018 Oct 30     [PubMed PMID: 30375121]


Von Korff M, Dublin S, Walker RL, Parchman M, Shortreed SM, Hansen RN, Saunders K. The Impact of Opioid Risk Reduction Initiatives on High-Dose Opioid Prescribing for Patients on Chronic Opioid Therapy. The journal of pain. 2016 Jan:17(1):101-10. doi: 10.1016/j.jpain.2015.10.002. Epub 2015 Oct 22     [PubMed PMID: 26476264]


Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2016 Mar 18:65(1):1-49. doi: 10.15585/mmwr.rr6501e1. Epub 2016 Mar 18     [PubMed PMID: 26987082]


Jung M, Xia T, Ilomäki J, Pearce C, Nielsen S. Opioid characteristics and nonopioid interventions associated with successful opioid taper in patients with chronic noncancer pain. Pain. 2024 Jun 1:165(6):1327-1335. doi: 10.1097/j.pain.0000000000003133. Epub 2023 Dec 19     [PubMed PMID: 38112755]


Els C, Jackson TD, Kunyk D, Lappi VG, Sonnenberg B, Hagtvedt R, Sharma S, Kolahdooz F, Straube S. Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews. The Cochrane database of systematic reviews. 2017 Oct 30:10(10):CD012509. doi: 10.1002/14651858.CD012509.pub2. Epub 2017 Oct 30     [PubMed PMID: 29084357]

Level 3 (low-level) evidence


Adler J, Mallick-Searle T, Garofoli M, Zimmerman A. Frontline Perspectives on Buprenorphine for the Management of Chronic Pain. Journal of multidisciplinary healthcare. 2024:17():1375-1383. doi: 10.2147/JMDH.S449748. Epub 2024 Mar 27     [PubMed PMID: 38563040]

Level 3 (low-level) evidence


Acampora G, Zhang Y. Chronic opioid pain treatment converted to buprenorphine: A case series using a 3-step low-dose incremental dosing guideline. Journal of opioid management. 2024 Jan-Feb:20(1):51-56. doi: 10.5055/jom.0822. Epub     [PubMed PMID: 38533715]

Level 2 (mid-level) evidence


Rattanavong M, Kwan D, Jorgenson D, Landry E, Marwah R, Halpape K. Low-dose Initiation of Buprenorphine/naloxone for the Management of Chronic Non-cancer Pain in Patients on Long-term Opioid Therapy: A Case Series. Canadian journal of pain = Revue canadienne de la douleur. 2024:8(1):2310811. doi: 10.1080/24740527.2024.2310811. Epub 2024 Jan 26     [PubMed PMID: 38571889]

Level 2 (mid-level) evidence


Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ (Clinical research ed.). 2009 Aug 12:339():b3002. doi: 10.1136/bmj.b3002. Epub 2009 Aug 12     [PubMed PMID: 19675082]


Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clinic proceedings. 2015 Apr:90(4):532-45. doi: 10.1016/j.mayocp.2015.01.018. Epub     [PubMed PMID: 25841257]


Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet. Neurology. 2015 Feb:14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7     [PubMed PMID: 25575710]

Level 1 (high-level) evidence


Albrecht PJ, Liu Y, Houk G, Ruggiero B, Banov D, Dockum M, Day AJ, Rice FL, Bassani G. Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine. Pain reports. 2024 Apr:9(2):e1119. doi: 10.1097/PR9.0000000000001121. Epub 2024 Feb 16     [PubMed PMID: 38375092]


Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. The Cochrane database of systematic reviews. 2019 Jan 23:1(1):CD007076. doi: 10.1002/14651858.CD007076.pub3. Epub 2019 Jan 23     [PubMed PMID: 30673120]

Level 1 (high-level) evidence


Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7:71(15):1183-90. doi: 10.1212/01.wnl.0000326598.83183.04. Epub 2008 Aug 20     [PubMed PMID: 18716236]

Level 1 (high-level) evidence


Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. The Cochrane database of systematic reviews. 2011 Jan 19:(1):CD005451. doi: 10.1002/14651858.CD005451.pub2. Epub 2011 Jan 19     [PubMed PMID: 21249671]

Level 1 (high-level) evidence


McQuay HJ, Tramèr M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain. 1996 Dec:68(2-3):217-27     [PubMed PMID: 9121808]

Level 1 (high-level) evidence


Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology. 2005 Jun:96(6):399-409     [PubMed PMID: 15910402]


Kaijankoski H, Nissen M, Ikäheimo TM, von Und Zu Fraunberg M, Airaksinen O, Huttunen J. Neuropathic Pain Medication and Antidepressant Use after Disability Pension in Patients with Spinal Cord Stimulation for Persistent Spinal Pain Syndrome. Pain research & management. 2024:2024():4953758. doi: 10.1155/2024/4953758. Epub 2024 Jan 31     [PubMed PMID: 38327724]


. Duloxetine (Cymbalta) for diabetic neuropathic pain. The Medical letter on drugs and therapeutics. 2005 Aug 15-29:47(1215-1216):67-8     [PubMed PMID: 16103866]

Level 3 (low-level) evidence


Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy or chronic pain. The Cochrane database of systematic reviews. 2009 Oct 7:(4):CD007115. doi: 10.1002/14651858.CD007115.pub2. Epub 2009 Oct 7     [PubMed PMID: 19821395]

Level 1 (high-level) evidence


Aiyer R, Barkin RL, Bhatia A. Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review. Pain medicine (Malden, Mass.). 2017 Oct 1:18(10):1999-2012. doi: 10.1093/pm/pnw261. Epub     [PubMed PMID: 27837032]

Level 1 (high-level) evidence


Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. The Cochrane database of systematic reviews. 2007 Apr 18:(2):CD004846     [PubMed PMID: 17443559]

Level 1 (high-level) evidence


Derry S, Wiffen PJ, Moore RA, Quinlan J. Topical lidocaine for neuropathic pain in adults. The Cochrane database of systematic reviews. 2014 Jul 24:2014(7):CD010958. doi: 10.1002/14651858.CD010958.pub2. Epub 2014 Jul 24     [PubMed PMID: 25058164]

Level 1 (high-level) evidence


Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. The Cochrane database of systematic reviews. 2010 Jun 16:(6):CD007402. doi: 10.1002/14651858.CD007402.pub2. Epub 2010 Jun 16     [PubMed PMID: 20556778]

Level 1 (high-level) evidence


Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain. Pain medicine (Malden, Mass.). 2010 Apr:11(4):535-49. doi: 10.1111/j.1526-4637.2010.00809.x. Epub 2010 Mar 4     [PubMed PMID: 20210866]


Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ (Clinical research ed.). 2004 Apr 24:328(7446):991     [PubMed PMID: 15033881]

Level 1 (high-level) evidence


Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain medicine (Malden, Mass.). 2010 Dec:11(12):1827-33. doi: 10.1111/j.1526-4637.2010.01003.x. Epub     [PubMed PMID: 21134121]

Level 1 (high-level) evidence


Nugent SM, Morasco BJ, O'Neil ME, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu'apuaka M, Paynter R, Kansagara D. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Annals of internal medicine. 2017 Sep 5:167(5):319-331. doi: 10.7326/M17-0155. Epub 2017 Aug 15     [PubMed PMID: 28806817]

Level 3 (low-level) evidence


Martimbianco ALC, Porfírio GJ, Pacheco RL, Torloni MR, Riera R. Transcutaneous electrical nerve stimulation (TENS) for chronic neck pain. The Cochrane database of systematic reviews. 2019 Dec 12:12(12):CD011927. doi: 10.1002/14651858.CD011927.pub2. Epub 2019 Dec 12     [PubMed PMID: 31830313]

Level 1 (high-level) evidence


Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA, Taylor RS. EFNS guidelines on neurostimulation therapy for neuropathic pain. European journal of neurology. 2007 Sep:14(9):952-70     [PubMed PMID: 17718686]

Level 1 (high-level) evidence


North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005:56(1):98-106; discussion 106-7     [PubMed PMID: 15617591]

Level 1 (high-level) evidence


Eldabe S, Kumar K, Buchser E, Taylor RS. An analysis of the components of pain, function, and health-related quality of life in patients with failed back surgery syndrome treated with spinal cord stimulation or conventional medical management. Neuromodulation : journal of the International Neuromodulation Society. 2010 Jul:13(3):201-9. doi: 10.1111/j.1525-1403.2009.00271.x. Epub 2010 Feb 22     [PubMed PMID: 21992833]

Level 2 (mid-level) evidence


de Vos CC, Meier K, Zaalberg PB, Nijhuis HJ, Duyvendak W, Vesper J, Enggaard TP, Lenders MW. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial. Pain. 2014 Nov:155(11):2426-31. doi: 10.1016/j.pain.2014.08.031. Epub 2014 Aug 29     [PubMed PMID: 25180016]

Level 1 (high-level) evidence


Hunter C, Davé N, Diwan S, Deer T. Neuromodulation of pelvic visceral pain: review of the literature and case series of potential novel targets for treatment. Pain practice : the official journal of World Institute of Pain. 2013 Jan:13(1):3-17. doi: 10.1111/j.1533-2500.2012.00558.x. Epub 2012 Apr 23     [PubMed PMID: 22521096]

Level 3 (low-level) evidence


Kapural L, Nagem H, Tlucek H, Sessler DI. Spinal cord stimulation for chronic visceral abdominal pain. Pain medicine (Malden, Mass.). 2010 Mar:11(3):347-55. doi: 10.1111/j.1526-4637.2009.00785.x. Epub 2010 Jan 15     [PubMed PMID: 20088856]


Lamer TJ, Moeschler SM, Gazelka HM, Hooten WM, Bendel MA, Murad MH. Spinal Stimulation for the Treatment of Intractable Spine and Limb Pain: A Systematic Review of RCTs and Meta-Analysis. Mayo Clinic proceedings. 2019 Aug:94(8):1475-1487. doi: 10.1016/j.mayocp.2018.12.037. Epub 2019 Jul 3     [PubMed PMID: 31279543]

Level 1 (high-level) evidence


Park CH, Lee SH. Relationships between the Spinal Dural Pulsations and the Short-Term Efficacy of Lumbar Epidural Steroid Injection. Pain research & management. 2024:2024():1824269. doi: 10.1155/2024/1824269. Epub 2024 Mar 18     [PubMed PMID: 38528984]


Sargut TA, Tkatschenko D, Früh A, Tüttenberg J, Heckert A, Fleck S, Kuckuck A, Bayerl SH. Study protocol for a prospective, randomized, multicenter trial to investigate the influence of peripheral nerve stimulation on patients with chronic sacroiliac joint syndrome (SILENCING). Trials. 2024 Mar 28:25(1):223. doi: 10.1186/s13063-024-08067-z. Epub 2024 Mar 28     [PubMed PMID: 38549128]

Level 1 (high-level) evidence


Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov:94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9. Epub     [PubMed PMID: 11690728]

Level 1 (high-level) evidence


Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. Journal of neurosurgery. 2008 Feb:108(2):292-8. doi: 10.3171/JNS/2008/108/2/0292. Epub     [PubMed PMID: 18240925]

Level 1 (high-level) evidence


Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA. 2006 Jul 5:296(1):87-93     [PubMed PMID: 16820551]

Level 1 (high-level) evidence


Holubek WJ, Kalman S, Hoffman RS. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology (Baltimore, Md.). 2006 Apr:43(4):880; author reply 882     [PubMed PMID: 16557558]

Level 3 (low-level) evidence


Jalan R, Williams R, Bernuau J. Paracetamol: are therapeutic doses entirely safe? Lancet (London, England). 2006 Dec 23:368(9554):2195-6     [PubMed PMID: 17189017]


Cavalcante AN, Sprung J, Schroeder DR, Weingarten TN. Multimodal Analgesic Therapy With Gabapentin and Its Association With Postoperative Respiratory Depression. Anesthesia and analgesia. 2017 Jul:125(1):141-146. doi: 10.1213/ANE.0000000000001719. Epub     [PubMed PMID: 27984223]


Gomes T, Greaves S, van den Brink W, Antoniou T, Mamdani MM, Paterson JM, Martins D, Juurlink DN. Pregabalin and the Risk for Opioid-Related Death: A Nested Case-Control Study. Annals of internal medicine. 2018 Nov 20:169(10):732-734. doi: 10.7326/M18-1136. Epub 2018 Aug 21     [PubMed PMID: 30140853]

Level 2 (mid-level) evidence


Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain physician. 2011 Mar-Apr:14(2):145-61     [PubMed PMID: 21412369]


Hayek SM, Veizi E, Hanes M. Treatment-Limiting Complications of Percutaneous Spinal Cord Stimulator Implants: A Review of Eight Years of Experience From an Academic Center Database. Neuromodulation : journal of the International Neuromodulation Society. 2015 Oct:18(7):603-8; discussion 608-9. doi: 10.1111/ner.12312. Epub 2015 Jun 5     [PubMed PMID: 26053499]


Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Thomson S, Raso L, Burton A, DeAndres J, Buchser E, Buvanendran A, Liem L, Kumar K, Rizvi S, Feler C, Abejon D, Anderson J, Eldabe S, Kim P, Leong M, Hayek S, McDowell G 2nd, Poree L, Brooks ES, McJunkin T, Lynch P, Kapural L, Foreman RD, Caraway D, Alo K, Narouze S, Levy RM, North R, Neuromodulation Appropriateness Consensus Committee. The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee. Neuromodulation : journal of the International Neuromodulation Society. 2014 Aug:17(6):571-97; discussion 597-8. doi: 10.1111/ner.12206. Epub     [PubMed PMID: 25112891]

Level 3 (low-level) evidence


Kumar K, Buchser E, Linderoth B, Meglio M, Van Buyten JP. Avoiding complications from spinal cord stimulation: practical recommendations from an international panel of experts. Neuromodulation : journal of the International Neuromodulation Society. 2007 Jan:10(1):24-33. doi: 10.1111/j.1525-1403.2007.00084.x. Epub     [PubMed PMID: 22151809]


Osborne MD, Ghazi SM, Palmer SC, Boone KM, Sletten CD, Nottmeier EW. Spinal cord stimulator--trial lead migration study. Pain medicine (Malden, Mass.). 2011 Feb:12(2):204-8. doi: 10.1111/j.1526-4637.2010.01019.x. Epub 2010 Dec 10     [PubMed PMID: 21143759]


Vallejo R, Kramer J, Benyamin R. Neuromodulation of the cervical spinal cord in the treatment of chronic intractable neck and upper extremity pain: a case series and review of the literature. Pain physician. 2007 Mar:10(2):305-11     [PubMed PMID: 17387353]

Level 3 (low-level) evidence


Wolter T, Kieselbach K. Cervical spinal cord stimulation: an analysis of 23 patients with long-term follow-up. Pain physician. 2012 May-Jun:15(3):203-12     [PubMed PMID: 22622904]

Level 2 (mid-level) evidence


North RB, Kidd DH, Petrucci L, Dorsi MJ. Spinal cord stimulation electrode design: a prospective, randomized, controlled trial comparing percutaneous with laminectomy electrodes: part II-clinical outcomes. Neurosurgery. 2005 Nov:57(5):990-6; discussion 990-6     [PubMed PMID: 16284568]

Level 1 (high-level) evidence


Henderson JM, Schade CM, Sasaki J, Caraway DL, Oakley JC. Prevention of mechanical failures in implanted spinal cord stimulation systems. Neuromodulation : journal of the International Neuromodulation Society. 2006 Jul:9(3):183-91. doi: 10.1111/j.1525-1403.2006.00059.x. Epub     [PubMed PMID: 22151706]


Bedder MD, Bedder HF. Spinal cord stimulation surgical technique for the nonsurgically trained. Neuromodulation : journal of the International Neuromodulation Society. 2009 Apr:12 Suppl 1():1-19. doi: 10.1111/j.1525-1403.2009.00194.x. Epub     [PubMed PMID: 22151467]


Rudiger J, Thomson S. Infection rate of spinal cord stimulators after a screening trial period. A 53-month third party follow-up. Neuromodulation : journal of the International Neuromodulation Society. 2011 Mar-Apr:14(2):136-41; discussion 141. doi: 10.1111/j.1525-1403.2010.00317.x. Epub 2010 Nov 4     [PubMed PMID: 21992200]

Level 2 (mid-level) evidence


Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. Journal of neurosurgery. 2004 Mar:100(3 Suppl Spine):254-67     [PubMed PMID: 15029914]


Turnbull DK, Shepherd DB. Post-dural puncture headache: pathogenesis, prevention and treatment. British journal of anaesthesia. 2003 Nov:91(5):718-29     [PubMed PMID: 14570796]


Costigan SN, Sprigge JS. Dural puncture: the patients' perspective. A patient survey of cases at a DGH maternity unit 1983-1993. Acta anaesthesiologica Scandinavica. 1996 Jul:40(6):710-4     [PubMed PMID: 8836266]

Level 3 (low-level) evidence


Petraglia FW 3rd, Farber SH, Gramer R, Verla T, Wang F, Thomas S, Parente B, Lad SP. The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. Neuromodulation : journal of the International Neuromodulation Society. 2016 Jan:19(1):85-90. doi: 10.1111/ner.12370. Epub 2015 Dec 8     [PubMed PMID: 26644210]