Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. METHODS: Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. RESULTS: In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. CONCLUSION: The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.

Variations in the management of fibromyalgia by physician specialty: rheumatology versus primary care.

PURPOSE: To evaluate the effect of physician specialty regarding diagnosis and treatment of fibromyalgia (FM) and assess the clinical status of patients initiating new treatment for FM using data from Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments. PATIENTS AND METHODS: Outpatients from 58 sites in the United States were enrolled. Data were collected via in-office surveys and telephone interviews. Pairwise comparisons by specialty were made using chi-square, Fisher's exact tests, and Student's t-tests. RESULTS: Physician specialist cohorts included rheumatologists (n=54), primary care physicians (n=25), and a heterogeneous group of physicians practicing pain or physical medicine, psychiatry, neurology, obstetrics and gynecology, osteopathy, or an unspecified specialty (n=12). The rheumatologists expressed higher confidence diagnosing FM (4.5 on a five-point scale) than primary care physicians (4.1) (P=0.037). All cohorts strongly agreed that recognizing FM is their responsibility. They agreed that psychological aspects of FM are important, but disagreed that symptoms are psychosomatic. All physician cohorts agreed with a multidisciplinary approach including nonpharmacological and pharmacological treatments, although physicians were more confident prescribing medications than alternative therapies. Most patients reported moderate to severe pain, multiple comorbidities, and treatment with several medications and nonpharmacologic therapies. CONCLUSION: Physician practice characteristics, physician attitudes, and FM patient profiles were broadly similar across specialties. The small but significant differences reported by physicians and patients across physician cohorts suggest that despite published guidelines, treatment of FM still contains important variance across specialties.

NSAIDs in the older patient: balancing benefits and harms.

OBJECTIVE: The older person is more likely to have pain since degenerative diseases and the effects of cancer are more common after 65 years of age. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used due to perceived safety, relatively low cost and over-the-counter availability. This brief review describes the necessity for, but risks of, NSAIDs in the older patient. DESIGN: A literature search was undertaken using PubMed and search terms including pain, aging, treatment, nonsteroidal anti-inflammatory drugs, arthritis, older patient, and guidelines. CONCLUSIONS: Pain complaints are common in the older population. Low back pain and osteoarthritis affects over two thirds of this group. Patients and clinicians are increasingly wary about treatment since no medication appears to be safe. Older patients opting for no treatment may have worsening function including decreased sleep, mobility, socialization, and increased depression. Ninety percent of all prescription NSAIDs are taken by patients over 65. Guidelines for safe use are available but frequently not followed by the practitioner including the FDA recommended "lowest dose possible for your treatment … for the shortest time needed." NSAIDs can be an effective treatment option for many older persons but caution should be exercised in this often fragile population.

Integrating health information technology and electronic health records into the management of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain condition that represents a significant economic burden for patients and health care systems. Effective treatment of FM requires a multidisciplinary management strategy that incorporates pharmacologic and nonpharmacologic therapy. Steps such as reducing the time to diagnosis and improving treatment decisions can result in significant cost savings and improved patient outcomes. An FM management framework, based on patient education and goal setting, has emphasized the need for ongoing care of patients with FM. In this article, we discuss how this framework could be further improved through the use of health information technology, including electronic health records. Health information technology/electronic health records can be incorporated at every stage of patient care, from initial presentation to diagnosis, through to making treatment decisions and maintaining ongoing patient management. This can lead to a number of potential benefits for patients with FM (by improving their level of care), primary care providers (by creating greater efficiencies), and the health care system (by reducing costs). Ultimately, the treatment and care of patients with FM need be no more burdensome to primary care providers than any other chronic illness. Through the greater efficiencies and optimized treatment approaches facilitated by health information technology/electronic health records, it should be possible to drive best-practice care for patients with FM and improve patient outcomes.

Comprehensive chronic pain management: improving physical and psychological function (CME multimedia activity).

As shown in this CME online activity (www.cmeaccess.com/AJM/ChronicPain02), chronic, non-cancer pain can arise from a variety of etiologies and can be broadly classified based on its underlying mechanism as nociceptive, inflammatory, neuropathic, or central, with some patients having pain arising from a combination of mechanisms. Chronic pain assessment and treatment involves evaluating not only its biological aspects, but also psychological and sociocultural factors. Beyond neural mechanisms, a patient's perception of chronic pain can be influenced by comorbid mood disorders, such as depression and anxiety; cognitive and affective traits, such as catastrophizing and fear-avoidance; environmental stressors, family relationships, social support, and cultural beliefs. Based on this biopsychosocial model, a multidisciplinary approach to management incorporates pharmacotherapy (opioid, nonopioid, and centrally-acting analgesics, and pain adjuvant medications) with nonpharmacologic physical rehabilitation and psychological and behavioral therapies to address the multifactorial causes of chronic pain, which in turn leads to improvement of physical and psychological function.

Managing chronic pain with nonopioid analgesics: a multidisciplinary consult.

As detailed in this online CME activity (www.cmeaccess.com/AJM/ChronicPain04), determining pain mechanism is an important aspect guiding treatment selection for chronic musculoskeletal pain states. Although broad classifications provide a framework, any combination of mechanisms may be present in a chronic pain patient, and there is growing evidence that pain states generally considered nociceptive may also involve elements of augmented central nervous system pain processing. Nonopioid analgesics, including serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and alpha-2-delta ligand anticonvulsants, are the treatments of choice for fibromyalgia and other central neuropathic pain states. Additionally, studies have now shown that certain SNRIs can be effective in treating "classic" nociceptive pain states, such as osteoarthritis, and also are effective for low back pain. In addition to considering biological mechanisms, chronic pain management also involves recognizing and evaluating the contribution of psychological and sociocultural factors that can influence pain chronicity and patient prognosis. A multimodal/multidisciplinary approach incorporating pharmacologic and nonpharmacologic therapy into a program that includes more than 1 discipline is important to improve outcomes in patients with chronic pain.

Clinical overview of fibromyalgia.

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide, more frequently in women than in men. In addition to chronic widespread pain, patients with FM usually experience other characteristic symptoms, including fatigue, disturbed sleep, stiffness, reduced functioning, dyscognition, and depressed mood. Many patients also have comorbid conditions such as depression, irritable bowel syndrome, temporomandibular disorder, or migraine. Although the etiology of FM remains unclear, evidence suggests that biologic, genetic, and environmental factors are involved. The variability of symptoms and the frequency of comorbidities among patients with FM make this a difficult disorder to diagnose. Diagnosis may be further complicated by the stigmatization of this disorder among treatment providers, the health insurance industry, and the general population. Treating chronic pain disorders such as FM can be time consuming and costly, and other issues such as polypharmacy, treatment adherence, and access to treatment often need to be addressed. The aim of this article is to provide physicians with a general overview of FM, including a brief review of the pathophysiology that explains the biologic and genetic bases of this disorder. Also included is a synopsis of new diagnostic criteria and other useful diagnostic tools and a discussion of various treatment challenges and strategies.

The science of fibromyalgia.

Fibromyalgia (FM) is a common chronic widespread pain disorder. Our understanding of FM has increased substantially in recent years with extensive research suggesting a neurogenic origin for the most prominent symptom of FM, chronic widespread pain. Neurochemical imbalances in the central nervous system are associated with central amplification of pain perception characterized by allodynia (a heightened sensitivity to stimuli that are not normally painful) and hyperalgesia (an increased response to painful stimuli). Despite this increased awareness and understanding, FM remains undiagnosed in an estimated 75% of people with the disorder. Clinicians could more effectively diagnose and manage FM if they better understood its underlying mechanisms. Fibromyalgia is a disorder of pain processing. Evidence suggests that both the ascending and descending pain pathways operate abnormally, resulting in central amplification of pain signals, analogous to the "volume control setting" being turned up too high. Patients with FM also exhibit changes in the levels of neurotransmitters that cause augmented central nervous system pain processing; levels of several neurotransmitters that facilitate pain transmission are elevated in the cerebrospinal fluid and brain, and levels of several neurotransmitters known to inhibit pain transmission are decreased. Pharmacological agents that act centrally in ascending and/or descending pain processing pathways, such as medications with approved indications for FM, are effective in many patients with FM as well as other conditions involving central pain amplification. Research is ongoing to determine the role of analogous central nervous system factors in the other cardinal symptoms of FM, such as fatigue, nonrestorative sleep, and cognitive dysfunction.

Improving the recognition and diagnosis of fibromyalgia.

Fibromyalgia (FM) is a chronic widespread pain disorder often seen in primary care practices. Advances in the understanding of FM pathophysiology and clinical presentation have improved the recognition and diagnosis of FM in clinical practice. Fibromyalgia is a clinical diagnosis based on signs and symptoms and is appropriate for primary care practitioners to make. The hallmark symptoms used to identify FM are chronic widespread pain, fatigue, and sleep disturbances. Awareness of common mimics of FM and comorbid disorders will increase confidence in establishing a diagnosis of FM.

Acute back pain: benefits and risks of current treatments.

OBJECTIVE: To review the efficacy and safety of current treatments for acute low back pain. RESEARCH DESIGN AND METHODS: PubMed was searched for clinical trials in which the words, acute, back, and pain all appeared in the study summary. The search was from the earliest references included in this database (1949) until 1 May 2009. This resulted in retrieval of 129 papers. Review of study summaries indicated that 36 provided information about either a topical treatment or oral therapy for acute low back pain. In addition, studies included as part of the evidence base for the Evidence Review of American Pain Society/American Academy of Pain Medicine Evidence Review for Evaluation and Management of Low Back Pain were reviewed. RESULTS: Recommended topical and systemic pharmacologic treatments for acute low back pain include application of superficial heat, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), skeletal muscle relaxants/benzodiazepines, and opioids including tramadol. Only a small number of studies compared different approaches to treatment of acute back pain and most failed to demonstrate significant differences among treatments. Available results support the view that both NSAIDs and low-level continuous heat treatment are more effective than acetaminophen and that heat treatment is also significantly more effective than ibuprofen. A potential limitation of this study is that information from trials published in journals not included in PubMed or reported only at meetings and not yet published was not included. CONCLUSIONS: A wide range of treatments is currently recommended for the management of patients with acute back pain and all are supported by results from controlled clinical trials.

Cannabinoids:their role in pain and palliation.

Controversy is associated with the issue of cannabis and cannabinoids in clinical care in the United States. Recent research has demonstrated the underlying mechanisms of cannabinoid analgesia via endocannabinoids, an endogenous system of retrograde neuromodulatory messengers that work in tandem with endogenous opioids. Additional receptor and non-receptor mechanisms of cannabinoid drugs have pertinent activity, including anti-carcinogenesis and neuroprotection, that may be of key importance in aging and terminal patient populations. The results of clinical trials with synthetic and plant-based cannabinoids suggest that the role of formulation and delivery system is critical in optimizing the risk-benefit profile of cannabinoid products. Synergy between opioids and cannabinoids may produce opioid-sparing effects, as well as extend the duration of analgesia and reduce opioid tolerance and dependence. This article reviews the mechanism of action of cannabinoids, examines marketed agents and those in clinical trials, and addresses their role in treatment of chronic pain, cancer, neurodegenerative diseases, and HIV/ AIDS. The ability of cannabinoid medicines to treat pain, associated sleep disorders, appetite loss, muscle spasm and a wide variety of other symptoms suggests that such agents may in the future play an important role in palliative care.