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. 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. Pain-related expenses exceed those for the costs of cancer, diabetes, and heart disease combined. 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 increased risk for 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.
Most patients who suffer from chronic pain complain of more than one type of pain. 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.
There are multiple categories and types of pain, which include neuropathic, nociceptive, musculoskeletal, inflammatory, psychogenic, and mechanical.
There are over 100 million people in the United States who would meet the criteria for chronic pain syndrome. 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. Elderly patients have been shown to receive up to 25% fewer pain medications compared to the average population.
Research has shown the lifetime prevalence for chronic pain patients attempting suicide to be between 5% and 14%; suicidal ideation was approximately 20%. Of the chronic patient patients who commit suicide, 53.6% died of firearm-related injuries, while 16.2% by opioid overdose.
History 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. Instead of pain, en elderly patient may complain of soreness or discomfort.
The Brief Pain Inventory (BPI) can be used to assess patients' beliefs on pain and the impact of pain on their lives. 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. 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. Furthermore, comorbid psychiatric disorders, such as major depressive disorder, can significantly delay the diagnosis of pain disorders. 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 a patient with underlying pain and a comorbid psychiatric disorder compared to patients without such comorbidity. 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.
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 two most commonly used tools. The MMPI-2 has been used more frequently for patients with chronic pain.
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 require 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. Pain may also worsen concurrent depression; thus, the treatment of pain has demonstrated to improve the responses to the treatments for depression. 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.
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. 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. 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  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, for patients with severe persistent pain or neuropathic pain secondary to malignancy, they may be warranted for pain management. 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. Opioid therapy should only start with extreme caution for patients with chronic musculoskeletal pain. 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.
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. Patients taking opioids at greater than 100 morphine milligram equivalents per day are at significantly increased risk 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. Long-acting opioids should only be used over short-acting opioids in the setting of disabling pain, causing severe impairment to quality of life.
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. 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. Adjunctive topical therapy, such as lidocaine or capsaicin cream, can be utilized as well.
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. There is limited evidence in the use of other antiepileptic medications in the treatment of 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.
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%.
The serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine is a useful treatment for both the treatment of chronic pain, osteoarthritis, and in the treatment of fibromyalgia. Furthermore, the efficacy of duloxetine in the treatment of comorbid depression is comparable to other antidepressants. Venlafaxine is an effective treatment for neuropathic pain, as well. A TCA can also be utilized, such as nortriptyline. TCA medications may require six to eight weeks to achieve its desired effect.
Adjunctive topical agents such as topical lidocaine are a useful treatment for neuropathic pain and allodynia as in postherpetic neuralgia. 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. Separately, topical capsaicin cream is an option for chronic neuropathic or musculoskeletal pain unresponsive to other treatments. Botulinum toxin has also demonstrated effectiveness in the treatment of postherpetic neuralgia. 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 the treatment of other types of chronic pain.
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. Deep brain stimulation is for post-stroke and facial pain as well as severe, intractable pain where other treatments have failed. 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. Spinal cord stimulators have shown a 50% reduction of pain compared to continued medical therapy.
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 fo 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 possibly from a 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.
The differential diagnosis for generalized chronic pain would include patients who develop allodynia from chronic opioids as well as 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 as well as 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.
Our current treatments for chronic pain can result in an estimated 30% decrease in a patient's pain scores. A thirty percent reduction in a patient's pain can have significant improvements to patients' function and quality of life. However, 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. 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 leads to significantly decreased quality of life, reduced productivity as well as 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. It is the most common cause of acute liver failure in the United States. Furthermore, hepatotoxicity can occur at therapeutic doses for patients with chronic liver disease.
Frequently used adjunct medications such as gabapentin or pregabalin can cause sedation, swelling, mood changes, confusion as well as respiratory depression in older patients who require additional analgesics. These agents require caution in elderly patients with painful diabetic neuropathy. Also, gabapentin or pregabalin, in combination with opioid analgesics, has been shown to increase the rate of patient mortality.
Duloxetine can cause mood changes, headaches, nausea as well as 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 . 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%. Most commonly, lead migration occurs, causing inadequate pain relief that can happen, often requiring revision and anchoring. Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra. Spinal cord stimulator lead fracture can occur in up to 9% of placements . Seromas are also very common and may require surgical incision and drainage. The risk of infection following a spinal cord stimulator placement is between 2.5 and 12 percent. 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. 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%.
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 that includes 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% . 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 as well as monitor for progression of symptoms. A team approach is an ideal way to limit the effects of chronic pain and its complications.
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 helping verify patient compliance with the treatment plan and monitor 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 [Level 2] and in minimizing the negative effects of chronic pain in the individual and society.
|||Nahin RL, Estimates of pain prevalence and severity in adults: United States, 2012. The journal of pain : official journal of the American Pain Society. 2015 Aug; [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; [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; [PubMed PMID: 22256802]|
|||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; [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; [PubMed PMID: 24612225]|
|||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; [PubMed PMID: 9736099]|
|||Tang NK,Crane C, Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychological medicine. 2006 May; [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; [PubMed PMID: 30208405]|
|||The management of persistent pain in older persons. Journal of the American Geriatrics Society. 2002 Jun; [PubMed PMID: 12067390]|
|||Closs SJ,Briggs M, Patients' verbal descriptions of pain and discomfort following orthopaedic surgery. International journal of nursing studies. 2002 Jul; [PubMed PMID: 11996877]|
|||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; [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; [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; [PubMed PMID: 19356853]|
|||Price DD, Psychological and neural mechanisms of the affective dimension of pain. Science (New York, N.Y.). 2000 Jun 9; [PubMed PMID: 10846154]|
|||Clark L,Jones K,Pennington K, Pain assessment practices with nursing home residents. Western journal of nursing research. 2004 Nov; [PubMed PMID: 15466611]|
|||Long CJ, The relationship between surgical outcome and MMPI profiles in chronic pain patients. Journal of clinical psychology. 1981 Oct; [PubMed PMID: 6458625]|
|||BECK AT,WARD CH,MENDELSON M,MOCK J,ERBAUGH J, An inventory for measuring depression. Archives of general psychiatry. 1961 Jun; [PubMed PMID: 13688369]|
|||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; [PubMed PMID: 16554392]|
|||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; [PubMed PMID: 25139618]|
|||Turk DC,Wilson HD,Cahana A, Treatment of chronic non-cancer pain. Lancet (London, England). 2011 Jun 25; [PubMed PMID: 21704872]|
|||Chou R,Qaseem A,Snow V,Casey D,Cross JT Jr,Shekelle P,Owens DK, 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; [PubMed PMID: 17909209]|
|||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; [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; [PubMed PMID: 18279766]|
|||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; [PubMed PMID: 15561731]|
|||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; [PubMed PMID: 19126235]|
|||Rasmussen-Barr E,Held U,Grooten WJ,Roelofs PD,Koes BW,van Tulder MW,Wertli MM, Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review. Spine. 2017 Apr 15; [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 AS,Stacey BR,Treede RD,Turk DC,Wallace MS, Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007 Dec 5; [PubMed PMID: 17920770]|
|||McNicol ED,Midbari A,Eisenberg E, Opioids for neuropathic pain. The Cochrane database of systematic reviews. 2013 Aug 29; [PubMed PMID: 23986501]|
|||Von Korff M,Kolodny A,Deyo RA,Chou R, Long-term opioid therapy reconsidered. Annals of internal medicine. 2011 Sep 6; [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; [PubMed PMID: 26017279]|
|||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; [PubMed PMID: 29509867]|
|||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, Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The journal of pain : official journal of the American Pain Society. 2009 Feb; [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; [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; [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 : official journal of the American Pain Society. 2016 Jan; [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; [PubMed PMID: 26987082]|
|||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; [PubMed PMID: 29084357]|
|||Freynhagen R,Bennett MI, Diagnosis and management of neuropathic pain. BMJ (Clinical research ed.). 2009 Aug 12; [PubMed PMID: 19675082]|
|||Gilron I,Baron R,Jensen T, Neuropathic pain: principles of diagnosis and treatment. Mayo Clinic proceedings. 2015 Apr; [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; [PubMed PMID: 25575710]|
|||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; [PubMed PMID: 30673120]|
|||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; [PubMed PMID: 18716236]|
|||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; [PubMed PMID: 21249671]|
|||McQuay HJ,Tramèr M,Nye BA,Carroll D,Wiffen PJ,Moore RA, A systematic review of antidepressants in neuropathic pain. Pain. 1996 Dec; [PubMed PMID: 9121808]|
|||Sindrup SH,Otto M,Finnerup NB,Jensen TS, Antidepressants in the treatment of neuropathic pain. Basic [PubMed PMID: 15910402]|
|||Duloxetine (Cymbalta) for diabetic neuropathic pain. The Medical letter on drugs and therapeutics. 2005 Aug 15-29; [PubMed PMID: 16103866]|
|||Lunn MP,Hughes RA,Wiffen PJ, Duloxetine for treating painful neuropathy or chronic pain. The Cochrane database of systematic reviews. 2009 Oct 7; [PubMed PMID: 19821395]|
|||Aiyer R,Barkin RL,Bhatia A, Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review. Pain medicine (Malden, Mass.). 2017 Oct 1; [PubMed PMID: 27837032]|
|||Khaliq W,Alam S,Puri N, Topical lidocaine for the treatment of postherpetic neuralgia. The Cochrane database of systematic reviews. 2007 Apr 18; [PubMed PMID: 17443559]|
|||Derry S,Wiffen PJ,Moore RA,Quinlan J, Topical lidocaine for neuropathic pain in adults. The Cochrane database of systematic reviews. 2014 Jul 24; [PubMed PMID: 25058164]|
|||Massey T,Derry S,Moore RA,McQuay HJ, Topical NSAIDs for acute pain in adults. The Cochrane database of systematic reviews. 2010 Jun 16; [PubMed PMID: 20556778]|
|||Haroutiunian S,Drennan DA,Lipman AG, Topical NSAID therapy for musculoskeletal pain. Pain medicine (Malden, Mass.). 2010 Apr; [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; [PubMed PMID: 15033881]|
|||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; [PubMed PMID: 21134121]|
|||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; [PubMed PMID: 28806817]|
|||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; [PubMed PMID: 31830313]|
|||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; [PubMed PMID: 17718686]|
|||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; [PubMed PMID: 15617591]|
|||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; [PubMed PMID: 21992833]|
|||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; [PubMed PMID: 25180016]|
|||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; [PubMed PMID: 22521096]|
|||Kapural L,Nagem H,Tlucek H,Sessler DI, Spinal cord stimulation for chronic visceral abdominal pain. Pain medicine (Malden, Mass.). 2010 Mar; [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; [PubMed PMID: 31279543]|
|||Farrar JT,Young JP Jr,LaMoreaux L,Werth JL,Poole RM, Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov; [PubMed PMID: 11690728]|
|||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; [PubMed PMID: 18240925]|
|||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; [PubMed PMID: 16820551]|
|||Holubek WJ,Kalman S,Hoffman RS, Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology (Baltimore, Md.). 2006 Apr; [PubMed PMID: 16557558]|
|||Jalan R,Williams R,Bernuau J, Paracetamol: are therapeutic doses entirely safe? Lancet (London, England). 2006 Dec 23; [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; [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; [PubMed PMID: 30140853]|
|||Lee M,Silverman SM,Hansen H,Patel VB,Manchikanti L, A comprehensive review of opioid-induced hyperalgesia. Pain physician. 2011 Mar-Apr; [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; [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, 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; [PubMed PMID: 25112891]|
|||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; [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; [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; [PubMed PMID: 17387353]|
|||Wolter T,Kieselbach K, Cervical spinal cord stimulation: an analysis of 23 patients with long-term follow-up. Pain physician. 2012 May-Jun; [PubMed PMID: 22622904]|
|||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; [PubMed PMID: 16284568]|
|||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; [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; [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; [PubMed PMID: 21992200]|
|||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; [PubMed PMID: 15029914]|
|||Turnbull DK,Shepherd DB, Post-dural puncture headache: pathogenesis, prevention and treatment. British journal of anaesthesia. 2003 Nov; [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; [PubMed PMID: 8836266]|
|||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; [PubMed PMID: 26644210]|