Continuing Education Activity

Over one-quarter of United States citizens suffer from chronic pain. It is among the most common complaints seen in an outpatient clinic. The failure to manage chronic pain, as well as the opioid dependence associated with chronic pain, can result in significant morbidity and mortality. This activity reviews and describes chronic pain, as well as the evaluation and treatment of chronic pain, and explains the role of the healthcare team in improving care for patients with this condition.

Objectives:

• Identify the epidemiology of chronic pain. - Sarosh we need to change
• Select the appropriate methodology to evaluate chronic pain, including physical exam, clinical history, and work-up.
• Apply best practices when managing chronic pain.
• Implement interprofessional team strategies for improving care coordination and communication to advance chronic pain and improve outcomes.

Introduction

Over one-quarter of United States citizens suffer from chronic pain.[1] It is among the most common complaints seen in an outpatient clinic. The failure to manage chronic pain and the opioid dependence associated with chronic pain can result in significant morbidity and mortality. One in five patient complaints in an outpatient clinic is related to pain, with over half of all patients seeing their primary care provider for one pain complaint or another. It is paramount primary care providers have a firm grasp on the management of patients with chronic pain. As a country, the United States spends well over 100 billion dollars a year on healthcare costs related to pain management and opioid dependence.[2] Pain-related expenses exceed those for the costs of cancer, diabetes, and heart disease combined.[3] 

How a patient's chronic pain gets managed can have profound and long-lasting effects on a patient's quality of life. The definition of chronic pain is any pain lasting longer than three months. There are multiple sources of chronic pain. Combination therapy for pain includes both pharmacological therapies and nonpharmacological treatment options. There is a more significant reduction in pain with combination therapy compared to a single treatment alone. Escalation of pharmacological therapy is in a stepwise approach. Comorbid depression and anxiety are widespread in patients with chronic pain. Patients with chronic pain are also at an increased risk of suicide. Chronic pain can impact every facet of a patient's life. Thus the diagnosis and appropriate management of patients experiencing chronic pain are critical.

Etiology

Most patients who suffer from chronic pain complain of more than one type of pain.[4] For example, a patient with chronic back pain may also have fibromyalgia. A significant percentage of patients suffer from a major depressive and generalized anxiety disorder. Over 67% of patients with chronic pain suffer from a comorbid psychiatric disorder.[5]

 There are multiple categories and types of pain, including neuropathic, nociceptive, musculoskeletal, inflammatory, psychogenic, and mechanical. 

Neuropathic Pain

• Peripheral neuropathic pain as the case post-herpetic neuralgia or diabetic neuropathy
• Central neuropathic pain - cerebral vascular accident sequella

Nociceptive Pain

• Pain due to actual tissue injuries such as burns, bruises, or sprains

Musculoskeletal Pain

• Back pain
• Myofascial pain

Inflammatory Pain

• Autoimmune disorders (rheumatoid arthritis)
• Infection 

Psychogenic Pain

• Pain caused by psychologic factors such as headaches or abdominal pain caused by emotional, psychological, or behavioral factors

Mechanical Pain 

• Expanding malignancy

Epidemiology

There are over 100 million people in the United States who would meet the criteria for chronic pain syndrome.[1] Over 20 million Americans suffer from debilitating chronic pain. Chronic regional pain is reported in 11.1 percent of chronic pain patients, while chronic back pain accounts for 10.1 percent, leg and foot pain 7.1 percent, arm and hand pain 4.1 percent, and headache 3.5 percent. There are reports of widespread pain in 3.6% of patients with chronic pain.[5] Elderly patients have been shown to receive up to 25% fewer pain medications than the average population.[6]

Research has shown the lifetime prevalence for chronic pain patients attempting suicide between 5% and 14%; suicidal ideation was approximately 20%.[7] Of the chronic patient patients who commit suicide, 53.6% died of firearm-related injuries, while 16.2% by opioid overdose.[8]

History and Physical

History and physical exam should include the onset of pain, description, mechanism of injury if applicable, location, radiation of pain, quality, severity, factors contributing to relief or worsening of the pain, frequency of the pain, and any breakthrough pain. A verbal numeric rating scale (VNRS) or number scale for pain is a common measure to determine the severity of pain, numbered from 0 to 10. This tool is commonly used for pain intensity.  Furthermore, associated symptoms should be assessed, such as muscle spasms or aches, temperature changes, restrictions to range of motion, morning stiffness, weakness, changes in muscle strength, changes in sensation, and hair, skin, or nail changes.

In addition to the patient's symptoms, the significance of the impact of the pain in day to day function should be discussed, as well as a review of the activities of daily living. It is important to understand how chronic pain affects the patient’s quality of life. Is pain impacting relationships or hobbies? Does the patient find themselves becoming depressed? Is the patient able to sleep throughout the night or exercise regularly? Can the patient go to work without limitations? Are activities of daily living affected, such as toileting, dressing, bathing, walking, or eating limited or restricted? 

Separately, a detailed neurologic exam on physical assessment should be completed, as well as an examination of the area of pain.

Older adults are a specific population that often identifies as suffering from chronic pain. The self-reporting of pain can be difficult in this population. Self-reporting of pain is essential for the identification and treatment of pain, while the inability to describe or communicate pain leads to undertreatment. Often elderly patients describe pain differently than the average population complicating diagnosis.[9][6] Instead of pain, an elderly patient may complain of soreness or discomfort.[10]

Evaluation

The Brief Pain Inventory (BPI) can assess patients' beliefs on pain and the impact of pain on their lives.[11][12] Separately, the McGill Pain Questionnaire (SF-MPQ-2) includes a drawing for the location of pain on the human body, a questionnaire regarding previous pain medication use, and past experiences with pain.[13] Neuropathic pain is assessable using the Neuropathic Pain Scale to follow responses to therapy.

Standard blood work and imaging are not indicated for chronic pain, but the clinician can order it when specific causes of pain are suspected. Thus they can be ordered on a case-by-case basis.

Psychiatric disorders can amplify pain signaling making symptoms of pain worse.[14] Furthermore, comorbid psychiatric disorders, such as major depressive disorder, can significantly delay the diagnosis of pain disorders.[15] Major depressive disorder and generalized anxiety disorder are the most common comorbid conditions related to chronic pain. There are twice as many prescriptions for opioids prescribed each year to patients with underlying pain and a comorbid psychiatric disorder compared to patients without such comorbidity.[10] Intuitively, this makes sense. For example, a patient suffering from depression often complain of fatigue, sleep changes, loss of appetite, decreased activity. These symptoms can make their pain worse over time. It is also crucial to realize patients with chronic pain are at an increased risk for suicide and suicidal ideation.[7][8]

Simultaneously screening for depression is recommended for patients with chronic pain. The Minnesota Multiphasic Personality Inventory-II (MMPI-2) or Beck's Depression Scale are the most commonly used tools. The MMPI-2 has been used more frequently for patients with chronic pain.[16][17]

Treatment / Management

Recommendations are to refer a patient to pain management in the case of debilitating pain, which is unresponsive to initial therapy. The pain may be located at multiple locations, requiring multimodal treatment or increases in dosages for adequate pain control or invasive procedures to control pain. Treatment of both pain and a comorbid psychiatric disorder leads to a more significant reduction of both pain and symptoms of the psychiatric disorder.[18] Pain may also worsen concurrent depression; thus, the treatment of pain has demonstrated to improve the responses to the treatments for depression.[19] There are multiple pharmacological, adjunct, nonpharmacological, and interventional treatments for chronic, severe, and persistent pain. 

The list of pharmacological options for chronic pain is extensive. This list includes nonopioid analgesics such as nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, and aspirin. Additionally, medications such as tramadol, opioids, antiepileptic drugs (gabapentin or pregabalin) can be useful. Furthermore, antidepressants such as tricyclic antidepressants and SNRI’s, topical analgesics, muscle relaxers, N-methyl-d-aspartate (NMDA) receptor antagonists, and alpha 2 adrenergic agonists are also possible pharmacological therapies. 

Treatment response can differ between individuals, but treatment is typically done in a stepwise fashion to reduce the duration and dosage of opioid analgesics. However, there is no singular approach appropriate for the treatment of pain in all patients.[20]

Chronic musculoskeletal pain is nociceptive pain. The treatment of such pain is in a stepwise approach but includes a combination of nonopioid analgesics, opioids, and nonpharmacological therapies. First-line therapy would be acetaminophen or NSAIDs. Both are effective for osteoarthritis and chronic back pain.[21][22][23] However, NSAIDs are relatively contraindicated in patients with a history of heart disease or myocardial infarction, renal disease, or patients on anticoagulation or with a history of ulcers.[24][25] There is limited evidence of which NSAID to use over another. One nonsteroidal antiinflammatory pharmacological agent may have a limited effect on a patient's pain while another may provide adequate pain relief. The recommendations are to try different agents before moving on to opioid analgesics [26] Failure to achieve appropriate pain relief with either acetaminophen or NSAIDs can lead to considering opioid analgesic treatment. 

Opioids are considered a second-line option; however, they may be warranted for pain management for patients with severe persistent pain or neuropathic pain secondary to malignancy.[27] There have been conflicting results on the use of opioids in neuropathic pain. However, for both short term and intermediate use, opioids are often used in the treatment of neuropathic pain.[28] Opioid therapy should only start with extreme caution for patients with chronic musculoskeletal pain.[29] Side effects of opioids are significant and frequent and may include opioid-induced hyperalgesia, constipation, dependence, and sedation. For chronic musculoskeletal pain, they are not superior to nonopioid analgesics.[30][31]

Administration of opioid analgesics is the recommendation when alternative pain medications have not provided adequate pain relief or contraindicated, as well as when pain is impacting the patient's quality of life, and the potential benefits outweigh the short and long-term effects of opioid therapy. The patient must make an informed choice before starting opioid treatment after discussing the risks, benefits, and alternatives to opioids.[30][32][33] Patients taking opioids at greater than 100 morphine milligram equivalents per day are at significantly increased risk of side effects. Side effects of opioids such as respiratory compromise will increase as the dosages increase. Patients with chronic pain could benefit from a therapy program designed to wean them from opioid analgesics to a safer dosage.[34][35] Long-acting opioids should only be used over short-acting opioids in the setting of disabling pain, causing severe impairment to quality of life.[36]

There is an estimated 78 percent risk of an adverse reaction to opioids such as constipation or nausea, while there is a 7.5 percent risk of developing a severe adverse reaction ranging from immunosuppression to respiratory depression.[37] Patients with chronic pain who meet the criteria for the diagnosis of opioid use disorder should receive the option of buprenorphine to treat their chronic pain. Buprenorphine is a considerably better alternative for patients with very high daily morphine equivalents who have failed to achieve adequate analgesia. 

Different types of pain also warrant different treatments. For example, chronic musculoskeletal back pain would be treated differently from severe diabetic neuropathy. A combination of multiple pharmacological therapies is often necessary to treat neuropathic pain. Less than 50% of patients with neuropathic pain will achieve adequate pain relief with a single agent.[38] Adjunctive topical therapy, such as lidocaine or capsaicin cream, can be utilized as well.[39][40]

The initial treatment of neuropathic is often with gabapentin or pregabalin. These are calcium channel alpha 2-delta ligands. They are indicated for postherpetic neuralgia, diabetic neuropathy, and mixed neuropathy.[41] There is limited evidence in 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 types of chronic neuropathic pain.[42][43]

Alternatively, antidepressants such as dual reuptake inhibitors of serotonin and norepinephrine (SNRI) or tricyclic antidepressants (TCA) can is an option. Antidepressants are beneficial in the treatment of neuropathic pain, central pain syndromes, and chronic musculoskeletal pain. For neuropathic pain, antidepressants have demonstrated a 50 percent reduction of pain relief. Fifty percent is a significant reduction, considering the average decrease in pain from various pain treatments is 30%.[44][45]

The serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine is useful in treating chronic pain, osteoarthritis, and the treatment of fibromyalgia.[46] Furthermore, the efficacy of duloxetine in the treatment of comorbid depression is comparable to other antidepressants.[47][44] Venlafaxine is an effective treatment for neuropathic pain, as well.[48] A TCA can also be utilized, such as nortriptyline. TCA medications may require six to eight weeks to achieve its desired effect.[27]

Adjunctive topical agents such as topical lidocaine are a useful treatment for neuropathic pain and allodynia as in postherpetic neuralgia.[49][50] Topical NSAIDs have been shown to improve acute musculoskeletal pain, such as a strain, but are less effective in chronic pain. Yet, topical NSAIDs are more effective than controls in the treatment of pain related to knee osteoarthritis.[51][52] Separately, topical capsaicin cream is an option for chronic neuropathic or musculoskeletal pain unresponsive to other treatments.[53] Botulinum toxin has also demonstrated effectiveness in the treatment of postherpetic neuralgia.[54] The use of cannabis is also an area of interest in pain research. There is some evidence that medical marijuana can be an effective treatment of neuropathic pain, while the evidence is currently limited in treating other types of chronic pain.[55]

The list of nonpharmacological therapies for chronic pain is extensive. Nonpharmacological 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 TENS units. Interventional techniques can also be utilized in the treatment of chronic pain. Spinal cord stimulation, epidural steroid injections, radiofrequency nerve ablations, botulinum toxin injections, nerve blocks, trigger point injections, and intrathecal pain pumps are some of the procedures and techniques commonly used to combat chronic pain. The efficacy of TENS units has been variable, and the results of TENS units for chronic pain management are inconclusive.[56] Deep brain stimulation is for post-stroke and facial pain as well as severe, intractable pain where other treatments have failed.[57] There is limited evidence of interventional approaches to pain management. For refractory pain, implantable intrathecal delivery systems are an option for patients who have exhausted all other options.

Spinal cord stimulators are an option for patients with chronic pain who have failed other conservative approaches. Most commonly, spinal cord stimulators are placed following failed back surgery but can also be an option for other causes of chronic pain such as complex regional pain syndrome, painful peripheral vascular disease, intractable angina, painful diabetic neuropathy, and visceral abdominal and perineal pain.[58][59][60][61][62] Spinal cord stimulators have shown a 50% reduction of pain compared to continued medical therapy.[63]

Differential Diagnosis

Pain is a symptom, not a diagnosis. Developing a differential diagnosis for a patient's chronic pain is based on assessing the possible underlying etiologies of the patient's pain. It is essential to determine what underlying injury or disease processes are responsible for the patient's pain since this requires identification for effective treatment. For instance, it is crucial to determine if a patient's neuropathic pain is peripheral or central. In another example, if a patient suffers from severe knee pain, it is essential to consider whether or not the knee pain is secondary to severe osteoarthritis since the patient may benefit from an injection or a possible knee replacement. In contrast, if the knee pain were instead related to a different condition such as rheumatoid arthritis, infection, gout, pseudogout, or meniscal injury, very different treatments would be necessary or indicated.

The differential diagnosis for generalized chronic pain would include patients who develop allodynia from chronic opioids and patients suffering from a major depressive disorder, as well as other psychiatric or sleep disorders, including insomnia. Furthermore, autoimmune diseases such as lupus or psoriatic arthritis, fibromyalgia, and central pain syndromes should be considered in states involving wide-spread, generalized chronic pain states. The four main categories of pain are neuropathic, musculoskeletal, mechanical, and inflammatory. Persistent and under-treated painful conditions can lead to chronic pain. Thus chronic pain is often a symptom of one or multiple diagnoses and can become its diagnosis as it becomes persistent and the body's neurochemistry changes. It is critical to treat acute and subacute pain before chronic pain develops. 

Prognosis

Our current chronic pain treatments can result in an estimated 30% decrease in a patient's pain scores.[20] A thirty percent reduction in a patient's pain can significantly improve patients' function and quality of life.[64] 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.[65] 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. 

Complications

Chronic pain leads to significantly decreased quality of life, reduced productivity, lost wages, worsening of chronic disease, and psychiatric disorders such as depression, anxiety, and substance abuse disorders. Patients with chronic pain are also at a significantly increased risk for suicide and suicidal ideation.

Many medications often used to treat chronic pain have potential risks and side effects and possible complications associated with their use.

Acetaminophen is a standard pharmacological therapy for patients with chronic pain. It is taken either as a single agent or in combination with an opioid. The hepatotoxicity occurs with acetaminophen when exceeding four grams per day.[66] It is the most common cause of acute liver failure in the United States.[67] Furthermore, hepatotoxicity can occur at therapeutic doses for patients with chronic liver disease.[68]

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.[69] These agents require caution in elderly patients with painful diabetic neuropathy. Also, gabapentin or pregabalin, combined with opioid analgesics, has been shown to increase the rate of patient mortality.[70]

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.

Feared complications of opioid therapy include addiction as well as overdose resulting in respiratory compromise. However, opioid-induced hyperalgesia is also a significant concern. Patients become more sensitive to painful stimuli while on chronic opioids.[71] 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. Also, there appears to be a dose-dependent risk of opioid overdose with increasing daily milligram morphine equivalents.

Complication rates for spinal could stimulators are high, ranging from five up to 40%.[72][73] Most commonly, lead migration occurs, causing inadequate pain relief, often requiring revision and anchoring.[74][75] Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra.[76][77] Spinal cord stimulator lead fracture can occur in up to 9% of placements.[78][79] Seromas are also very common and may require surgical incision and drainage.[80][72] The risk of infection following a spinal cord stimulator placement is between 2.5 and 12 percent.[81][82] 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.[83][84][80] The most significant adverse to spinal cord stimulator placement would be a spinal epidural hematoma. This emergency would require immediate neurosurgical decompression of the hematoma. The incidence of a spinal epidural hematoma is 0.71%.[85]

Deterrence and Patient Education

• Chronic pain management is best with an interprofessional team, including a primary care physician and a pain management specialist.
• A multimodal treatment approach is optimal to effect better pain control and outcomes as well as to minimize the need for high-risk treatments such as opioids.
• Pain medication dosages are to be increased gradually and in a stepwise approach.
• Dosages are titrated as needed, slowly according to the patient's pain.
• Medications for opioid addiction should be offered to patients on chronic opioids if there is any concern for opioid dependence or misuse.
• Clinicians can provide interventional procedures to patients with chronic pain refractory to medications or patients wishing who need weaning down or off of chronic opioid treatment.
• Management of comorbid depression and anxiety is paramount in the reduction of chronic pain.
• The elderly population may describe pain differently than the average population.
• Following spinal cord stimulator implantation, the patient should be seen by their pain provider periodically to make adjustments to the settings of the stimulator to maximize its effectiveness.
• Patients with chronic pain should be monitored closely for severe depression and any suicidal ideation and plan.

Enhancing Healthcare Team Outcomes

Chronic pain is a significant condition that affects many millions of people and is an important public health concern with considerable morbidity and mortality. Thus chronic pain is best managed with a multimodal and interprofessional approach. Managing chronic pain requires an interprofessional team of healthcare professionals, including a primary care physician, nursing team, pharmacist, and pain medicine specialists. Without proper management, the patient's quality of life can have a deleterious impact.  The evaluation and treatment of such patients are paramount.

Chronic pain correlates with several severe complications, including severe depression and suicide attempts and ideation. The lifetime prevalence for chronic pain patients attempting suicide attempt was shown to be between 5% and 14%; suicidal ideation was approximately 20% [7]. These complications often require psychiatric intervention and advanced pharmacological or interventional therapies. Severe symptoms must receive treatment immediately, leading to an increase in healthcare costs. It is of the utmost importance to identify the risk factors and perform a thorough assessment of the patient with chronic and monitor for progression of symptoms. A team approach is an ideal way to limit the effects of chronic pain and its complications. 

• Evaluation of a patient with acute pain by the primary care provider to prevent the progression of chronic pain is the recommended first step.
• Conservative chronic pain management should begin when symptoms are mild or moderate, including physical therapy, cognitive-behavioral therapy, and pharmacological management.
• A pharmacist or other expert knowledgeable in the medications frequently utilized to treat chronic pain should evaluate the medication regimen to include medication reconciliation to preclude any drug-drug interactions and alert the healthcare team regarding any concerns.
• The patient should follow up with a primary care provider as well as other specialists as necessary regularly to assess and effectively treat the patient's pain.
• Clinicians must address comorbid psychiatric disorders. This action may require the involvement of a psychiatrist, depending on the severity of the patient's symptoms.
• If symptoms worsen on follow up or if there is a concerning escalation of pharmacological therapy such as with opioids, a referral to a pain medicine specialist merit consideration.
• If the patient has exhausted various pharmacological and nonpharmacological treatment options, interventional procedures can be considered.
• If the patient expresses concern for suicidal ideation or plan at any time, an emergent psychiatric team should evaluate the patient immediately.
• Patients who have developed opioid dependence secondary to pharmacological therapy should be offered treatment, possibly referral for addiction treatment or detoxification if indicated. The patient should be put on a medication weaning schedule or possibly medications to treat opioid dependence.
• Based on CDC recommendations, patients on high-dose opioid medications or patients with risk factors for opioid overdose (e.g., obesity, sleep apnea, concurrent benzodiazepine use, etc.) should receive naloxone at home for the emergent treatment of an unintentional overdose.

The interprofessional team should openly discuss and communicate clearly about the management of each patient so that the patient receives optimal care delivery. This area is where nursing can play a crucial role by verifying patient compliance with the treatment plan and monitoring for progress (or lack of) with the present treatment plan. Nursing can help monitor for adverse medication side effects and communicate any areas of concern to the treating physicians. Effective, open interprofessional communication is crucial in the optimal management of chronic pain and minimizing the negative effects of chronic pain in the individual and society. [Level 2]