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Chronic Pain Syndromes: How to Break the Cycle, Part 1


Pain is a significant public health concern. In a prevalence study conducted in Australia, 17% of men and 20% of women reported chronic daily pain. A US study found that 13% of the total workforce had lost productive time during a 2-week period because of a pain condition. Headache, back pain, and arthritis pain headed the list of causes.

ABSTRACT: Understanding a patient's specific pain pathophysiology is the key to successful therapy. Nociceptive pain tends to respond to different treatments than neuropathic and psychogenic pain. Initial options for patients with chronic pain may include physical therapy; cognitive behavioral therapy; oral analgesics; and minimally invasive pain procedures, such as epidural corticosteroid injections. Certain medications (eg, tricyclic antidepressants and anticonvulsants) can be helpful in patients with neuropathic pain. Consider surgery for patients with refractory pain and for those whose pain has an identifiable cause that will respond favorably to surgery. 

Pain is a significant public health concern. In a prevalence study conducted in Australia, 17% of men and 20% of women reported chronic daily pain.1 A US study found that 13% of the total workforce had lost productive time during a 2-week period because of a pain condition.2 Headache, back pain, and arthritis pain headed the list of causes.

Despite the growth of pain medicine as a specialty and the increasing number of pain centers, primary care physicians evaluate and treat most patients with pain. These patients can present numerous challenges.

Diagnosis is the first hurdle, since few reliable diagnostic tests are available for many pain conditions. Treatment options are often limited and may not be covered by medical insurance. There are sometimes legal issues regarding disability and liability. In general, patients with pain syndromes tend to consume a great deal of office time and resources.

In this 2-part article, we will explore the diagnosis and treatment of 3 pain syndromes. Here, following an overview of diagnostic principles and the available treatment modalities, we focus on osteoarthritis pain. In a coming issue, we will discuss the diagnosis and treatment of trigeminal neuralgia and radicular low back pain.

Diagnosis is crucial on several levels. First, it is essential to exclude progressive or serious conditions as soon as possible so that intervention can be timely. In addition, clarification of the type of pain (nociceptive or non-nociceptive) can increase the likelihood of successful treatment even in some previously intractable cases. Nociceptive pain (somatic and visceral), resulting from active stimulation of pain nerve endings caused by tissue damage or inflammation, tends to respond to different treatments than non-nociceptive (neurogenic and psychogenic) pain. (Table 1 lists clues to differentiating neuropathic from nociceptive pain). Also, the development of a lowered pain threshold (sensitization), which can occur peripherally as well as centrally, can be treated successfully if it is identified early.

The idea that understanding a patient's specific pain pathophysiology is the key to successful therapy is a relatively new one, but it is changing the face of pain management.3 Throughout this article, we will attempt to illustrate this principle.

Medication. Billions of dollars are spent each year on over-the-counter analgesics. For many patients with chronic pain, the limited effectiveness of these agents leads to overuse, adverse effects, and increased frustration. Overuse of NSAIDs can have serious GI and renal consequences and may affect cardiac health as well.

Opioids are effective in many patients with chronic pain, but they require judicious prescribing and monitoring.4 Opioids are all capable of producing adverse effects, including nausea, constipation, edema, pruritus, seizures, sleep disturbances, endocrine dysfunction, and tolerance, which can limit their use. High-dose opioids can also be associated with the development of opioid hyperal-gesia, the paradoxical response in which opioid treatment may worsen pain. The tendency of some patients to overuse prescription opioids for their euphoric properties and the increasing street value of some of these medications have dramatically altered the prescribing practices of many clinicians.

Many effective prophylactic medications are available for patients with chronic pain, especially if it is of neuropathic origin. These fall primarily into 3 main categories:

• Antidepressants, including tricyclic antidepressants and mixed norepinephrine and serotonin reuptake inhibitors (duloxetine and venlafaxine). Selective serotonin reuptake inhibitors do not seem to have independent analgesic activity.
• Anticonvulsants.
• Various agents, including antispasmodic medications, such as tizanidine and baclofen; muscle relaxants, such as orphenadrine; and neuroleptic/antiemetic medications, such as chlorpromazine.

Minimally invasive procedures. In the hands of a skilled pain specialist with a background in interventional pain management, procedures have proved beneficial to many patients with chronic pain. Techniques include local nerve infiltration with lidocaine, bupivacaine, and other local anesthetics. The addition of corticosteroid agents has been proposed as a way to prolong and strengthen the effect of these anesthetics through their ability to modify inflammation and block nociceptive C-fiber conduction.5 Epidural corticosteroid treatment, spinal cord stimulation, and intrathecal analgesic infusions have gained popularity. Although there is biochemical and clinical support for epidural corticosteroid therapy, randomized controlled trials are needed to determine which patients will benefit the most from this technique. Trigger point injections may be no more effective for pain conditions than placebo transcutaneous electrical nerve stimulation, although there are avid proponents of the technique.

Behavioral medicine techniques. Relaxation training, biofeedback, and cognitive-behavioral training can be helpful in patients with chronic pain. Two key requirements are skilled practitioners and motivated patients.

Surgery. This is an attractive option for patients with a suspected mechanical cause of pain. Often, however, well-intentioned surgical procedures may prove unhelpful, even with excellent morphological outcome. Thus "failed-back" and "failed-neck" patients abound. For patients with truly intractable pain, neurolysis, gangliectomy, dorsal root entry zone (DREZ) lesioning, and other invasive procedures can be considered. Neural stimulation helps some patients, including those with persistent radicular pain after lumbosacral spine surgery.

Management of psychiatric comorbidities. It is essential to identify and address the psychiatric comorbidities found in many patients with chronic pain. Many are significantly frustrated by their illness, sometimes to the point of suicidal ideation. These issues must be addressed, ideally by a psychologist or a psychiatrist with experience in chronic pain management. Secondary gain must be explored when this possibility exists. Substance abuse potential should also be monitored. Table 2 lists possible psychiatric accompaniments in patients with chronic pain.

Osteoarthritis is the most prevalent form of arthritis. It is projected that more than 59 million persons in the United States (18% of the population) will have osteoarthritis by 2020.6 This noninflammatory rheumatologic condition is associated with nociceptive pain. One of the joints most commonly affected is the knee. Osteoarthritis of the knee poses the highest associated risk of mobility disability (assistance needed with ambulation) compared with other medical disorders in persons 65 years and older.

The pathogenesis of osteoarthritis is characterized by alterations in articular cartilage. Persons with osteoarthritis also have changes in subchondral bone, menisci, ligaments, synovium, and periarticular muscles.7 Risk factors for osteoarthritis include:

• Genetic factors.
• Congenital and traumatic deformities associated with malalignment.
• Aging.
• Female sex.
• Occupational activity.
• Obesity.

Diagnosis. The diagnosis of osteoarthritis is based on the history, physical findings, and results of radiographic imaging. Clinical features of the disease include joint pain with activity, morning stiffness lasting less than 30 minutes, instability, reduced range of motion, joint crepitus, and local swelling. Laboratory values such as complete blood cell (CBC) count, erythrocyte sedimentation rate, and C-reactive protein level are in the normal range, and synovial fluid analysis does not indicate an inflammatory or septic condition. Radiographic imaging can be helpful in confirming the diagnosis; however, radiographs may be normal in persons with osteoarthritis and the findings do not correlate with the severity of pain.8Treatment. The treatment of osteoarthritis is based on the severity of symptoms. Treatment begins with nonpharmacological management, including education, physical therapy, weight loss, and gait analysis, and progresses to pharmacological management and surgery as the disease and symptoms become more severe.

Nonpharmacological management. A recent meta-analysis demonstrated that exercise and self-management interventions lead to significant improvement in physical health and well-being.9 A physical therapy program should include isokinetic or isotonic strengthening and should be structured to help patients improve their ability to perform activities of daily living. Range of motion exercises and isometric exercises do not seem to be helpful. Refer the patient to a physical therapist who is able to analyze and determine the proper alignment of joints because certain exercises to increase strength may actually amplify the rate of structural damage. Pool therapy is often very helpful because it unloads joints while allowing the patient to participate in physical activity. A physical therapist can also provide unloading (eg, cane) and realignment devices (eg, braces and taping).8Oral medications. Most of the pharmacological treatments for osteoarthritis modify pain severity but do not stop or reverse the underlying disease process. Options include NSAIDs, acetaminophen, and opioids.

NSAIDs have an opioid-sparing effect (a reduction in the dose of opioid pain medications required without sacrificing pain control) of approximately 20% to 35%, but they also have a dose ceiling. Before NSAID therapy is initiated, basic laboratory studies, such as a CBC count and a metabolic profile, are often helpful to determine whether the patient has any preexisting conditions that would limit NSAID use. These agents are associated with renal, liver, cardiac, and GI morbidity.

An attempt can be made to reduce the adverse GI effects by choosing a relatively more selective COX-2/COX-1 NSAID (eg, etodolac, nabumetone, or meloxicam). A proton pump inhibitor may be prescribed for certain patients who take NSAIDs and who have associated risk factors for GI morbidity (eg, elderly persons, cigarette smokers, and patients with a history of peptic ulcer disease). A combination of diclofenac and misoprostol has been shown to reduce gastric ulcer formation. H2-blockers are not as effective in reducing GI ulcers from NSAIDs. The single most important risk factor for GI bleeding is the duration of therapy.

Furthermore, NSAIDs are highly protein-bound drugs and, therefore, can potentiate the effects of many other medications, including anticoagulants (ie, warfarin), diuretics, oral hypoglycemic agents, and anticonvulsants. NSAIDs can also inhibit the antiplatelet effects of aspirin.10

Although acetaminophen is associated with fewer adverse effects than NSAIDs, it has less ability to control pain. Acetaminophen and NSAIDs should not be used in combination because of the risk of papillary necrosis with secondary interstitial nephritis.

If NSAIDs and acetaminophen are unsuccessful at controlling pain or if there is a relative contraindication to their use, opioids can be prescribed. Opioids do not have a dose ceiling, but they are associated with adverse effects and the possibility of abuse and other aberrant drug-taking behaviors (ie, behaviors that stray from the regulations of the opioid contract).

Future research is being dedicated to the development of chondroprotective drugs (eg, tumor necrosis factor-αblocking agents).11

Recently, much attention has been given to glucosamine and chondroitin sulfate. Early research suggested that they were effective in reducing pain and decreasing functional impairment from symptomatic osteoarthritis. The recent Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) implied that these supplements did not reduce pain in a majority of patients with knee osteoarthritis, although a subgroup analysis suggested that they may be effective in patients with moderate to severe osteoarthritis.12 The recommend ed dosage is 1500 mg/d.13Topical agents. To avoid the systemic effects of NSAIDs, opioids, and acetaminophen, topical agents have been developed for osteoarthritis. The lidocaine patch 5%, capsaicin cream 0.025% and 0.075%, and topical NSAIDs are effective in the treatment of primary osteoarthritis of the knee. Currently, topical NSAIDs have been approved in the United States for only acute use.14 Topical capsaicin should be applied 3 or 4 times a day; it often takes 2 to 6 weeks before patients notice significant relief.

Other modalities. More invasive therapeutic interventions for osteoarthritis include viscosupplementation and intra-articular corticosteroids. Viscosupplementation involves the intra-articular injection of hyaluronan and hylan derivatives in order to restore viscoelasticity of the joint and thereby decrease pain and improve mobility. Definitive conclusions about the effectiveness of intra-articular viscosupplementation cannot be made. A recent meta-analysis suggests viscosupplementation is an effective treatment for osteoarthritis, but the improvements in pain, function, and patient global assessment are relatively minor.15 Viscosupplementation seems to have a more prolonged analgesic effect than intra-articular corticosteroids.

Intra-articular steroids are effective in the short term (1 to 3 weeks) but do not seem to possess long-lasting analgesic or functional effects.16 Some authors have suggested resting the joint after a corticosteroid injection for a minimum of 24 hours to prolong efficacy.17

Cognitive-behavioral therapy. This therapy, which involves training in relaxation techniques, cognitive restructuring, problem-solving skills, and habit reversal, can improve outcomes in patients who have chronic pain associated with osteoarthritis. It is well documented that pain catastrophizing (cognitive and emotional processes that magnify pain-related stimulation) often leads to an increase in the severity of reported pain in persons who have arthritis.18 Cognitive-behavioral therapy (CBT) can help identify and treat pain-related catastrophizing. CBT is also effective for trigeminal neuralgia and lumbar radicular pain, which will be discussed in Part 2 of this article in a coming issue.19

Surgery. Consider osteotomy and joint replacement for patients whose pain resists conservative therapy. Among properly selected patients, 95% will have good to excellent results.7

Acknowledgment: The authors thank Dana Dellapiazza, DO, for her editorial and technical assistance.




Blyth FM, March LM, Brnabic AJ, et al. Chronic pain in Australia: a prevalence study. Pain. 2001;89: 127-134.


Stewart WF, Ricci JA, Chee E, et al. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003;290:2443-2454.


Woolf CJ; American College of Physicians; American Physiological Society. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140: 441-451.


Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. 1986;25:171-186.


McLain RF, Kapural L, Mekhail NA. Epidural steroids for back and leg pain: mechanism of action and efficacy. Cleve Clin J Med. 2004;71:961-970.


Sharma L, Kapoor D, Issa S. Epidemiology of osteoarthritis: an update. Curr Opin Rheumatol. 2006;18:147-156.


Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006; 332:639-642.


Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841-848.


Devos-Comby L, Cronan T, Roesch SC. Do exercise and self-management interventions benefit patients with osteoarthritis of the knee? A metaanalytic review. J Rheumatol. 2006;33:744-756.


Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809-1817.


Verbruggen G. Chondroprotective drugs in degenerative joint diseases. Rheumatology (Oxford). 2006;45:129-138.


Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006; 354:795-808.


Fox BA, Schmitz ED, Wallace R. FPIN's clinical inquiries. Glucosamine and chondroitin for osteoarthritis. Am Fam Physician. 2006;73:1245-1246.


Roth SH, Shainhouse JZ. Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial. Arch Intern Med. 2004;164:2017-2023.


Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2):CD005321.


Bellamy N, Campbell J, Robinson V, et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2): CD005328.


Cole BJ, Schumacher HR Jr. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg. 2005;13:37-46.


Edwards RR, Bingham CO 3rd, Bathon J, Haythornthwaite JA. Catastrophizing and pain in arthritis, fibromyalgia, and other rheumatic diseases. Arthritis Rheum. 2006;55:325-332.


McCracken LM, Turk DC. Behavioral and cognitive-behavioral treatment for chronic pain: outcome, predictors of outcome, and treatment process. Spine. 2002;27:2564-2573.

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