Publications
  • Yue HJ, Guilleminault C.
    Med Clin North Am. 2010 May;94(3):435-46.

    There has been a growing recognition of chronic pain that may be experienced by patients. There has been a movement toward treating these patients aggressively with pharmacologic and nonpharmacologic modalities. Opioids have been a significant component of the treatment of acute pain, with their increasing use in cases of chronic pain, albeit with some controversy. In addition to analgesia, opioids have many accompanying adverse effects, particularly with regard to stability of breathing during sleep. This article reviews the existing literature on the effects of opioids on sleep, particularly sleep-disordered breathing.

    Opioid medication and sleep-disordered breathing.

    Yue HJ, Guilleminault C.
    Med Clin North Am. 2010 May;94(3):435-46.

    There has been a growing recognition of chronic pain that may be experienced by patients. There has been a movement toward treating these patients aggressively with pharmacologic and nonpharmacologic modalities. Opioids have been a significant component of the treatment of acute pain, with their increasing use in cases of chronic pain, albeit with some controversy. In addition to analgesia, opioids have many accompanying adverse effects, particularly with regard to stability of breathing during sleep. This article reviews the existing literature on the effects of opioids on sleep, particularly sleep-disordered breathing.

  • Zorro O, Labato-Polo J, Kano H, et al.
    Neurology 2009;73:1149-54
    .
    Background: Surgical options for multiple sclerosis (MS) related to trigeminal neuralgia (TN), a severe and disabling pain disorder, include percutaneous rhizotomy, stereotactic radiosurgery, or microsurgical nerve section. Our goal was to evaluate clinical outcomes after gamma knife radio-surgery (GKRS) in patients with MS with TN.
    Methods: We evaluated clinical outcomes in 37 patients with TN managed over a 12-year period. The maximum TN target dose varied between 70 and 90 Gy. Seventy-eight percent of patients had failed prior surgery. In 9, GKRS was the first procedure. Median follow-up was 56.7 months (range, 6–174). Pain relief was assessed in each patient by physicians who did not participate in the surgery.

    Results: Eventual complete pain relief (BNI grade I) after GKRS and reasonable pain control (BNI grade I–IIIb) after GKRS were noted in 23 patients (62.1%) and 36 patients (97.3%) at some point in their course. Reasonable pain control (BNI grade I–IIIb) after GKRS was maintained in 82.6%, 73.9%, and 54.0% of patients after 1, 3, and 5 years. Fourteen patients (37.8%) underwent a second or a subsequent procedure for residual or recurrent pain. Eight patients underwent a second GKRS, 5 underwent percutaneous glycerol rhizotomy, and 1 underwent balloon micro-compression. The complication rate after GKRS was 5.4% (new onset of nondisabling paresthesias). No patient developed dysesthesias.

    Conclusions:
    Gamma knife radiosurgery is the most minimally invasive surgical technique for multiple sclerosis–related trigeminal neuralgia and has low morbidity. For this reason, gamma knife radiosurgery proved to be a satisfactory management strategy for multiple sclerosis–related trigeminal neuralgia.

    Gamma knife radiosurgery for multiple sclerosis–related trigeminal neuralgia.

    Zorro O, Labato-Polo J, Kano H, et al.
    Neurology 2009;73:1149-54
    .
    Background: Surgical options for multiple sclerosis (MS) related to trigeminal neuralgia (TN), a severe and disabling pain disorder, include percutaneous rhizotomy, stereotactic radiosurgery, or microsurgical nerve section. Our goal was to evaluate clinical outcomes after gamma knife radio-surgery (GKRS) in patients with MS with TN.
    Methods: We evaluated clinical outcomes in 37 patients with TN managed over a 12-year period. The maximum TN target dose varied between 70 and 90 Gy. Seventy-eight percent of patients had failed prior surgery. In 9, GKRS was the first procedure. Median follow-up was 56.7 months (range, 6–174). Pain relief was assessed in each patient by physicians who did not participate in the surgery.

    Results: Eventual complete pain relief (BNI grade I) after GKRS and reasonable pain control (BNI grade I–IIIb) after GKRS were noted in 23 patients

  • Allen KD, Eugene OZ, Coffman CJ, et al.
    Osteoarthritis Cartilage. 2009 Oct 1.

    Objective: This study examined factors underlying racial differences in pain and function among patients with hip and / or knee osteoarthritis (OA). Methods: Participants were n=491 African Americans and Caucasians enrolled in a clinical trial of telephone-based OA self-management. Arthritis Impact Measurement Scales-2 (AIMS2) pain and function subscales were obtained at baseline. Potential explanatory variables included arthritis self-efficacy, AIMS2 affect subscale, problem- and emotion-focused pain coping, demographic characteristics, body mass index, self-reported health, joint(s) with OA, symptom duration, pain medication use, current exercise, and AIMS2 pain subscale (in models of function). Variables associated with both race and pain or function, and which reduced the association of race with pain or function by ≥10%, were included in final multivariable models. Results: In simple linear regression models, African Americans had worse scores than Caucasians on AIMS2 pain (B=0.65, p=0.001) and function (B=0.59, p<0.001) subscales. In multivariable models race was no longer associated with pain (B=0.03, p=0.874) or function (B=0.07, p=0.509), indicating these associations were accounted for by other covariates. Variables associated with worse AIMS2 pain and function were: worse AIMS2 affect scores, greater emotion-focused coping, lower arthritis self-efficacy, and fair or poor self-reported health. AIMS2 pain scores were also significantly associated with AIMS2 function. Conclusion: Factors explaining racial differences in pain and function were largely psychological, including arthritis self-efficacy, affect, and use of emotion-focused coping. Selfmanagement and psychological interventions can influence these factors, and greater dissemination among African Americans may be a key step toward reducing racial disparities in pain and function.

    Racial Differences in Osteoarthritis Pain and Function: Potential Explanatory Factors

    Allen KD, Eugene OZ, Coffman CJ, et al.
    Osteoarthritis Cartilage. 2009 Oct 1.

    Objective: This study examined factors underlying racial differences in pain and function among patients with hip and / or knee osteoarthritis (OA). Methods: Participants were n=491 African Americans and Caucasians enrolled in a clinical trial of telephone-based OA self-management. Arthritis Impact Measurement Scales-2 (AIMS2) pain and function subscales were obtained at baseline. Potential explanatory variables included arthritis self-efficacy, AIMS2 affect subscale, problem- and emotion-focused pain coping, demographic characteristics, body mass index, self-reported health, joint(s) with OA, symptom duration, pain medication use, current exercise, and AIMS2 pain subscale (in models of function). Variables associated with both race and pain or function, and which reduced the association of race with pain or function by ≥10%, were included in final multivariable models.

  • Russell IJ, Crofford LJ, Leon T, et al.
    Sleep Med. 2009 Jun;10(6):604-10. Epub 2009 May 1.
    OBJECTIVES: Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM.
    METHODS: Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients' global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain.
    RESULTS: A total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48-50 years, on average had FM for 9-10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P<0.001), MOS Sleep Disturbance (P<0.01), MOS Quantity of Sleep (P<0.003), and MOS Sleep Problems Index scores (P<0.02) relative to placebo. Treatment effects for the 450mg and 600mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43-80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief. CONCLUSIONS: These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients' insomnia, while the remainder occurred through the drug's analgesic activity.

    The Effects of Pregabalin on Sleep Disturbance Symptoms Among Individuals with Fibromyalgia Syndrome

    Russell IJ, Crofford LJ, Leon T, et al.
    Sleep Med. 2009 Jun;10(6):604-10. Epub 2009 May 1.
    OBJECTIVES: Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM.
    METHODS: Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients' global impressions of change.

    Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of

  • Zimmerman ME, Pan JW, Hetherington HP, et al.
    Neurology. 2009;73(19):1567-70.

    BACKGROUND: Few neuroimaging investigations of pain in elderly adults have focused on the hippocampus, a brain structure involved in nociceptive processing that is also subject to involution associated with dementing disorders. The goal of this pilot study was to examine MRI- and magnetic resonance spectroscopy (MRS)-derived hippocampal correlates of pain in older adults. METHODS: A subset of 20 nondemented older adults was drawn from the Einstein Aging Study, a community-based sample from the Bronx, NY. Pain was measured on 3 time scales: 1) acute pain right now (pain severity); 2) pain over the past 4 weeks (Short Form-36 Bodily Pain); 3) chronic pain over the past 3 months (Total Pain Index). Hippocampal data included volume data normalized to midsagittal area and N-acetylaspartate to creatine ratios (NAA/Cr). RESULTS: Smaller hippocampal volume was associated with higher ratings on the Short Form-36 Bodily Pain (r(s) = 0.52, p = 0.02) and a nonsignificant trend was noted for higher ratings of acute pain severity (r(s) = -0.44, p = 0.06). Lower levels of hippocampal NAA/Cr were associated with higher acute pain severity (r(s) = -0.45, p = 0.05). Individuals with chronic pain had a nonsignificant trend for smaller hippocampal volumes (t = 2.00, p = 0.06) and lower levels of hippocampal NAA/Cr (t = 1.71, p = 0.10). CONCLUSIONS: Older adults who report more severe acute or chronic pain have smaller hippocampal volumes and lower levels of hippocampal N-acetylaspartate/creatine, a marker of neuronal integrity. Future studies should consider the role of the hippocampus and other brain structures in the development and experience of pain in healthy elderly and individuals with Alzheimer disease.

    Hippocampal correlates of pain in healthy elderly adults: a pilot study.

    Zimmerman ME, Pan JW, Hetherington HP, et al.
    Neurology. 2009;73(19):1567-70.

    BACKGROUND: Few neuroimaging investigations of pain in elderly adults have focused on the hippocampus, a brain structure involved in nociceptive processing that is also subject to involution associated with dementing disorders. The goal of this pilot study was to examine MRI- and magnetic resonance spectroscopy (MRS)-derived hippocampal correlates of pain in older adults. METHODS: A subset of 20 nondemented older adults was drawn from the Einstein Aging Study, a community-based sample from the Bronx, NY. Pain was measured on 3 time scales: 1) acute pain right now (pain severity); 2) pain over the past 4 weeks (Short Form-36 Bodily Pain); 3) chronic pain over the past 3 months (Total Pain Index). Hippocampal data included volume data normalized to midsagittal area and N-acetylaspartate to creatine ratios (NAA/Cr).

    RESULTS: Smaller hippocampal volume was

  • Stojanovic MP, Sethee J, Mohiuddin M, et al.
    Clin J Pain. 2010;26(2):110-5.

    OBJECTIVES: To determine the correlation between magnetic resonance imaging (MRI) pathology and the response to diagnostic facet medial branch block (MBB) and L5 dorsal ramus medial branch block and radiofrequency (RF) denervation of lumbar facet joints. METHODS: The medical records of 127 consecutive patients who underwent MBB for suspected zygapophysial joint pain were reviewed. The lumbar spine MRI of these patients was systematically graded by 2 musculoskeletal radiologists for loss of disc height, spinal stenosis, facet joint degeneration, and other forms of spinal pathology. RESULTS: Patients with central or foraminal spinal stenosis had statistically significant correlation with positive outcome of RF (P=0.02), but not with MBB (P=0.08). The presence of facet joint degeneration or hypertrophy was positively correlated with response to MBB (71% vs. 51%; P=0.04), but not RF. Loss of disc height did not correlate with outcome of MBB (P=0.08) and RF (P=0.29). For other spinal pathology, no significant differences were noted for either the response to diagnostic blocks or the RF denervation. Younger patients were more likely to fail MBB (P<0.01) but not RF denervation (P=0.38). DISCUSSION: Whereas some relationships were noted between MRI findings and the response to lumbar facet joint interventions, many of these correlations tended to be weak. However, this study does suggest the possibility that patients with spinal stenosis, often considered an exclusion criterion for facet interventions, may respond to RF denervation of facet joints. Prospective studies are needed to confirm these observations.

    MRI analysis of the lumbar spine: can it predict response to diagnostic and therapeutic facet procedures?

    Stojanovic MP, Sethee J, Mohiuddin M, et al.
    Clin J Pain. 2010;26(2):110-5.

    OBJECTIVES: To determine the correlation between magnetic resonance imaging (MRI) pathology and the response to diagnostic facet medial branch block (MBB) and L5 dorsal ramus medial branch block and radiofrequency (RF) denervation of lumbar facet joints. METHODS: The medical records of 127 consecutive patients who underwent MBB for suspected zygapophysial joint pain were reviewed. The lumbar spine MRI of these patients was systematically graded by 2 musculoskeletal radiologists for loss of disc height, spinal stenosis, facet joint degeneration, and other forms of spinal pathology. RESULTS: Patients with central or foraminal spinal stenosis had statistically significant correlation with positive outcome of RF (P=0.02), but not with MBB (P=0.08). The presence of facet joint degeneration or hypertrophy was positively correlated with response to MBB (71% vs.

    51%;

  • Chou R, Fanciullo GJ, Fine PG, et al.
    J Pain. 2009;10:113-130.
    Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices.

    Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

    Chou R, Fanciullo GJ, Fine PG, et al.
    J Pain. 2009;10:113-130.
    Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids.

    The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic

  • Strassels SA.
    J Manag Care Pharm. 2009;15(7):556-62
    BACKGROUND: Prescription opioid abuse and its associated costs are a problem in the United States, with significant epidemiologic and economic consequences. The breadth and depth of these consequences are not fully understood at present.
    OBJECTIVE: To summarize published, English-language biomedical evidence pertaining to the epidemiology and costs of prescription opioid analgesic misuse and abuse and to describe efforts to reduce the burden of
    these problems.
    METHODS: Published English-language articles on the epidemiology and economics of abuse, misuse, or diversion of prescribed opioid analgesics in the United States were identified by searching PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health Literature database (CINAHL), EconLit, and PsycInfo, using (economics OR epidemiology) AND (misuse OR abuse) AND opioid as search terms or Medical Subject Heading (MeSH) terms. Article bibliographies were also searched manually for applicable papers. The search was limited to articles published from 1995 through July 2009.
    RESULTS: The literature search identified 2,347 titles, of which all but 41 were excluded as not pertaining specifically to the epidemiology or economics of prescription opioid abuse or misuse in the United States. In 2006, approximately 5.2 million individuals in the United States reported using prescription analgesics nonmedically in the prior month, up from 4.7 million in 2005. The total cost of prescription opioid abuse in 2001 was estimated at $8.6 billion, including workplace, health care, and criminal justice expenditures. One study of commercially insured beneficiaries in the United States found that mean per-capita annual direct health care costs from 1998 to 2002 were nearly $16,000 for abusers of prescription and nonprescription opioids compared with approximately $1,800 for nonabusers who had at least 1 prescription insurance claim.
    CONCLUSIONS: The economic burden of prescription opioid misuse and abuse is large. While the existing evidence indicates that persons who abuse or misuse prescription opioids incur higher costs and health care
    resource use, differences in methods used to explore this question make estimating the actual societal burden imposed by this problem difficult. Efforts to establish and maintain a balance between access to these drugs
    for legitimate pain management while decreasing the risk of abuse and misuse are critically important and include such tools as patient and provider education, patient screening, and use of technology.

    Economic Burden of Prescription Opioid Misuse and Abuse

    Strassels SA.
    J Manag Care Pharm. 2009;15(7):556-62
    BACKGROUND: Prescription opioid abuse and its associated costs are a problem in the United States, with significant epidemiologic and economic consequences. The breadth and depth of these consequences are not fully understood at present.
    OBJECTIVE: To summarize published, English-language biomedical evidence pertaining to the epidemiology and costs of prescription opioid analgesic misuse and abuse and to describe efforts to reduce the burden of
    these problems.


    METHODS: Published English-language articles on the epidemiology and economics of abuse, misuse, or diversion of prescribed opioid analgesics in the United States were identified by searching PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health Literature database (CINAHL), EconLit, and PsycInfo, using (economics OR epidemiology) AND (misuse OR abuse) AND opioid as search terms or Medical Subject Heading

  • Journal of the American Geriatrics Society. 2009 Jul 1.
    Persistent pain is often complex and multifactorial in older patients, who often underreport pain. Multiple comorbidities can complicate pain assessment and treatment. Older persons are also more likely to experience medication-related side effects and complications related to diagnostic and invasive procedures. The American Geriatrics Society (AGS) has recently published a the Clinical Practice Guideline on management of chronic pain in older persons, which aims to update the evidence base of the 2002 Guideline and provide recommendations regarding newer pharmacological approaches to managing persistent pain in the older population. This guideline was developed by a panel comprising experts in pain management, pharmacology, rheumatology, neurology, nursing, palliative care, and geriatric clinical practice. The panel reviewed evidence-based literature published since the 2002 AGS guidelines and then drafted new recommendations. More than 24,000 citations were identified. Of these, approximately 2,400 abstracts were screened for evidence-based content and detailed summaries were created for more than 240 full-text English-language articles. Data from these formal meta-analyses, randomized controlled trials, and other clinical trials were reviewed to determine the strength and quality of evidence based on a modified version of the Grading of Recommendations Assessment, Development, and Evaluation Working Group that developed by the American College of Physicians for their Guideline Grading System. Through a consensus process, panel members assigned strength and quality of evidence to each recommendation.

    Pharmacological Management of Persistent Pain in Older Persons

    Journal of the American Geriatrics Society. 2009 Jul 1.
    Persistent pain is often complex and multifactorial in older patients, who often underreport pain. Multiple comorbidities can complicate pain assessment and treatment. Older persons are also more likely to experience medication-related side effects and complications related to diagnostic and invasive procedures. The American Geriatrics Society (AGS) has recently published a the Clinical Practice Guideline on management of chronic pain in older persons, which aims to update the evidence base of the 2002 Guideline and provide recommendations regarding newer pharmacological approaches to managing persistent pain in the older population. This guideline was developed by a panel comprising experts in pain management, pharmacology, rheumatology, neurology, nursing, palliative care, and geriatric clinical practice.

    The panel reviewed evidence-based literature published since the 2002 AGS

  • Strouse TB.
    J Palliat Med. 2009 Aug 20. 

    Opioid analgesics are crucial for pain management in most patients receiving palliative care. Contemporary models advocate for the provision of palliative care services as early as possible in a course of illness, suggesting that many patients will receive palliative care services, and opioids, concurrent with complex disease-modifying therapies. This article reviews the metabolic pathways of commonly prescribed opioid analgesics and provides a survey of what is known about how disease-modifying therapies alter the pharmacokinetics and pharmacodynamics of opioids. Existing treatment guidelines are reviewed. Practical suggestions are offered.

    Pharmacokinetic Drug Interactions in Palliative Care: Focus On Opioids.

    Strouse TB.
    J Palliat Med. 2009 Aug 20. 

    Opioid analgesics are crucial for pain management in most patients receiving palliative care. Contemporary models advocate for the provision of palliative care services as early as possible in a course of illness, suggesting that many patients will receive palliative care services, and opioids, concurrent with complex disease-modifying therapies. This article reviews the metabolic pathways of commonly prescribed opioid analgesics and provides a survey of what is known about how disease-modifying therapies alter the pharmacokinetics and pharmacodynamics of opioids. Existing treatment guidelines are reviewed. Practical suggestions are offered.