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1.  Persistent Pain and Frailty: A Case For Homeostenosis 
Persistent pain is associated with poorer health outcomes and may lead to increased vulnerability and diminished physiologic reserve, ultimately precipitating frailty. To test for the existence of this process, we compared the association of self-reported moderate to severe pain with the presence of frailty.
Cross-sectional analysis of the Canadian Study of Health and Aging-Wave 2.
Community dwellers
Representative sample of persons age 65 and older in Canada.
Pain (exposure) was categorized as no or very mild pain versus moderate or greater pain. Frailty (outcome) was operationalized as the accumulation of 33 possible self-reported health attitudes, illnesses, and functional abilities, subsequently divided into tertiles (i.e. not frail, pre-frail, and frail). Multivariable logistic regression assessed for the association of pain with frailty.
Of participants who reported moderate or greater pain (35.5% or 1,765 out of 4,968), 16.2% were not frail, 34.1% were pre-frail, and 49.8%were frail. For persons with moderate or greater pain compared to those with mild or no pain, the odds of being pre-frail compared to not frail were higher by a factor of 2.52 (95% confidence interval (CI)=2.13-2.99; p<0.05). For persons with moderate or greater pain compared to those with mild or no pain, the odds of being frail compared to not frail was higher by a factor of 5.52 (CI=4.49-6.64; p<0.05).
Moderate or higher pain was independently associated with the presence of frailty. While we cannot ascertain causality in a cross-sectional analysis, interventions to improve pain management may help prevent or ameliorate frailty.
PMCID: PMC3258356  PMID: 22150394
Pain; frailty; older adults; homeostenosis
2.  Disability Transitions and Health Expectancies among Adults 45 Years and Older in Malawi: A Cohort-Based Model 
PLoS Medicine  2013;10(5):e1001435.
Collin Payne and colleagues investigated development of disabilities and years expected to live with disabilities in participants 45 years and older participating in the Malawi Longitudinal Survey of Families and Health.
Please see later in the article for the Editors' Summary
Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited.
Methods and Findings
Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%–64%) of their remaining 28 y of life (95% CI, 25.7–33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%–46%) of their remaining 25.4 y (95% CI, 23.3–28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being.
Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
The population of the world is getting older. In almost every country, the over-60 age group is growing faster than any other age group. In 2000, globally, there were about 605 million people aged 60 years or more; by 2050, 2 billion people will be in this age group. Much of this increase in the elderly population will be in low-income countries. In sub-Saharan Africa, for example, 10% of the population is currently aged 45 years or more, but by 2060, a quarter of the population will be so-called mature adults. In all countries, population aging is the result of women having fewer children (falling fertility) and people living longer (increasing life expectancy). Thus, population aging is a demographic transition, a change in birth and death rates. In low- and middle-income countries, population aging is occurring in parallel with an “epidemiological transition,” a shift from communicable (infectious) diseases to non-communicable diseases (for example, heart disease) as the primary causes of illness and death.
Why Was This Study Done?
Both the demographic and the epidemiological transition have public health implications for low-income countries. Good health is important for the independence and economic productivity of older people. Productive older people can help younger populations financially and physically, and help compensate for the limitations experienced by younger populations infected with HIV. Also, low-income countries lack social safety nets, so disabled older adults can be a burden on younger populations. Thus, the health of older individuals is important to the well-being of people of all ages. As populations age, low-income countries will need to invest in health care for mature and elderly adults and in disease prevention programs to prevent or delay the onset of non-communicable diseases, which can limit normal daily activities by causing disabilities. Before providing these services, national policy makers need to know the proportion of their population with disabilities, the functional limitations caused by poor physical health, and the health expectancies (the number of years a person can expect to be in good health) of older people in their country. In this cohort modeling study, the researchers estimate health expectancies and transition rates between different levels of disability among mature adults in Malawi, one of the world's poorest countries, using data collected by the Malawi Longitudinal Survey of Families and Health (MLSFH) on economic, social, and health conditions in a rural population. Because Malawi has shorter life expectancies and earlier onset of disability than wealthier countries, the authors considered individuals aged 45 and older as mature adults at risk for disability.
What Did the Researchers Do and Find?
The researchers categorized the participants in the 2006, 2008, and 2010 waves of the MLSFH into three levels of functional limitation (healthy, moderately limited, and severely limited) based on answers to questions in the SF-12 health survey questionnaire that ask about disabilities that limit daily activities that rural Malawians perform. The researchers estimated age–gender patterns of functional limitations and transition rates between different disability states using a discrete-time hazard model, and health expectancies by running a microsimulation to model the aging of synthetic cohorts with various starting ages but the same gender and functional limitation distributions as the study population. These analyses show that the chance of becoming physically disabled rises sharply with age, with 45-year-old women in rural Malawi expected to spend 58% of their estimated remaining 28 years with functional limitations, and 45-year-old men expected to live 41% of their remaining 25.4 years with functional limitations. Also, on average, a 45-year-old woman will spend 2.7 years with moderate functional limitation and 0.6 years with severe functional limitation before she reaches 55; for men the corresponding values are 1.6 and 0.4 years. Around 50% of moderately and 60%–80% of severely limited individuals stated that pain interfered quite a bit or extremely with their normal work during the past four weeks, suggesting that pain treatment may help reduce disability.
What Do These Findings Mean?
These findings suggest that mature adults in rural Malawi will have some degree of disability during much of their remaining lifetime. The risks of experiencing functional limitations are higher and the onset of persistent disabilities happens earlier in Malawi than in more developed contexts—the proportions of remaining life spent with severe limitations at age 45 in Malawi are comparable to those of 80-year-olds in the US. The accuracy of these findings is likely to be affected by assumptions made during modeling and by the quality of the data fed into the models. Nevertheless, these findings suggest that functional limitations, which have a negative effect on the labor activity of individuals, will become more prominent in Malawi (and probably other sub-Saharan countries) as the age composition of populations shifts over the coming years. Older populations in sub-Saharan Africa are not targeted well by health policies and programs at present. Consequently, these findings suggest that policy makers will need to ensure that additional financial resources are provided to improve health-care provision for aging individuals and to lessen the high rates of functional limitation and associated disabilities.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Andreas Stuck, et al.
The World Health Organization provides information on many aspects of aging (in several languages); the WHO Study on Global Ageing and Adult Health (SAGE) is compiling longitudinal information on the health and well-being of adult populations and the aging process
The United Nations Population Fund and HelpAge International publication Ageing in the Twenty-First Century is available
HelpAge International is an international nongovernmental organization that helps older people claim their rights, challenge discrimination, and overcome poverty, so that they can lead dignified, secure, and healthy lives
More information on the Malawi Longitudinal Study of Families and Health is available
PMCID: PMC3646719  PMID: 23667343
3.  Persistent pain in a community-based sample of children and adolescents: Sex differences in psychological constructs 
The prevalence of persistent and recurrent pain among children and adolescents has important economic, social and psychological repercussions. The impact of chronic pain in children extends beyond the affected individuals – more than one-third of parents of children with pain report clinically significant levels of stress and depression. Although many pain-related psychological factors have been examined in chronic pediatric pain populations, much of that research involved clinical samples. Community-based research, however, is necessary to uncover the way pain is experienced by youth, regardless of whether treatment is sought or is available. This study aimed to ascertain the lifetime prevalence of pediatric pain in a Canadian community-based sample, and to explore age and sex differences in children who report persistent pain and those who do not with respect to several constructs believed to play important roles in the development and maintenance of persistent pain.
Very few studies have investigated the psychological factors associated with the pain experiences of children and adolescents in community samples.
To examine the lifetime prevalence of, and psychological variables associated with, persistent pain in a community sample of children and adolescents, and to explore differences according to sex, age and pain history.
Participants completed the Childhood Anxiety Sensitivity Index (CASI), the Child Pain Anxiety Symptoms Scale (CPASS), the Multidimensional Anxiety Scale for Children-10 (MASC-10), the Pain Catastrophizing Scale for Children (PCS-C) and a pain history questionnaire that assessed chronicity and pain frequency. After research ethics board approval, informed consent/assent was obtained from 1022 individuals recruited to participate in a study conducted at the Ontario Science Centre (Toronto, Ontario).
Of the 1006 participants (54% female, mean [± SD] age 11.6±2.7 years) who provided complete data, 27% reported having experienced pain that lasted for three months or longer. A 2×2×2 (pain history, age and sex) multivariate ANOVA was conducted, with the total scores on the CASI, the CPASS, the MASC-10 and the PCS-C as dependent variables. Girls with a history of persistent pain expressed higher levels of anxiety sensitivity (P<0.001) and pain catastrophizing (P<0.001) than both girls without a pain history and boys regardless of pain history. This same pattern of results was found for anxiety and pain anxiety in the older, but not the younger, age group.
Boys and girls appear to differ in terms of how age and pain history relate to the expression of pain-related psychological variables. Given the prevalence of persistent pain found in the study, more research is needed regarding the developmental implications of persistent pain in childhood and adolescence.
PMCID: PMC3206778  PMID: 22059200
Children; Persistent pain; Psychosocial factors; Sex differences
4.  A systematic review of early prognostic factors for persistent pain following acute orthopedic trauma 
Persistent or chronic pain is prevalent in many developed countries, with estimates ranging from 10% to higher than 50%, and is a major economic burden to individuals and societies. However, the variation in pain outcomes after acute orthopedic trauma and treatment confronts treating physicians with uncertainty in providing prognostic advice regarding long-term recovery. Although several previous reviews have addressed the determinants of chronic pain outcomes secondary to acute trauma, they have primarily focused on specific injury samples and, furthermore, lack consistency with respect to the important prognostic factors, which limits the generalizability of findings. This review, however, aimed specifically to identify the early prognostic factors associated with variation in persistent pain outcomes following acute orthopedic trauma presenting with a spectrum of pathologies.
Acute orthopedic trauma contributes substantially to the global burden of disease.
The present systematic review aimed to summarize the current knowledge concerning prognostic factors for the presence of persistent pain, pain severity and pain-related disability following acute orthopedic trauma involving a spectrum of pathologies to working-age adults.
The Ovid MEDLINE and EMBASE databases were searched for level II prognostic studies published between January 1996 and October 2010. Studies that were longitudinal and reported results with multivariate analyses appropriate for prognostic studies were included. Studies that addressed two specific injury types that have been the subject of previous reviews, namely, injuries to the spinal column and amputations, were excluded.
The searches yielded 992 studies; 10 studies met the inclusion criteria and were rated for methodological quality. Seventeen factors were considered in more than one cohort. There was strong evidence supporting the association of female sex, older age, high pain intensity, preinjury anxiety or depression, and fewer years of education with persistent pain outcomes. There was moderate evidence supporting the association between postinjury depression or anxiety with persistent pain, and that injury severity was not a risk factor for ongoing pain.
Many individuals experience persistent pain following acute trauma. Due to the lack of studies, the use of different constructs to measure the same factor and the methodological limitations associated with many of the studies, the present review was only able to reliably identify a limited set of factors that predicted persistent pain. Recommendations for the conduct of future methodologically rigorous studies of persistent pain are provided.
PMCID: PMC3299034  PMID: 22518366
Acute trauma; Biopsychosocial prognosis; Orthopedic; Pain measurement; Pain outcomes; Systematic review
5.  How Well Do Clinical Pain Assessment Tools Reflect Pain in Infants? 
PLoS Medicine  2008;5(6):e129.
Pain in infancy is poorly understood, and medical staff often have difficulty assessing whether an infant is in pain. Current pain assessment tools rely on behavioural and physiological measures, such as change in facial expression, which may not accurately reflect pain experience. Our ability to measure cortical pain responses in young infants gives us the first opportunity to evaluate pain assessment tools with respect to the sensory input and establish whether the resultant pain scores reflect cortical pain processing.
Methods and Findings
Cortical haemodynamic activity was measured in infants, aged 25–43 wk postmenstrual, using near-infrared spectroscopy following a clinically required heel lance and compared to the magnitude of the premature infant pain profile (PIPP) score in the same infant to the same stimulus (n = 12, 33 test occasions). Overall, there was good correlation between the PIPP score and the level of cortical activity (regression coefficient = 0.72, 95% confidence interval [CI] limits 0.32–1.11, p = 0.001; correlation coefficient = 0.57). Of the different PIPP components, facial expression correlated best with cortical activity (regression coefficient = 1.26, 95% CI limits 0.84–1.67, p < 0.0001; correlation coefficient = 0.74) (n = 12, 33 test occasions). Cortical pain responses were still recorded in some infants who did not display a change in facial expression.
While painful stimulation generally evokes parallel cortical and behavioural responses in infants, pain may be processed at the cortical level without producing detectable behavioural changes. As a result, an infant with a low pain score based on behavioural assessment tools alone may not be pain free.
Rebeccah Slater and colleagues show that although painful stimulation generally evokes parallel cortical and behavioral responses in infants, pain may produce cortical responses without detectable behavioral changes.
Editors' Summary
Pain is a sensory and emotional experience. It is normally triggered by messages transmitted from specialized receptors (nociceptors) in the body to integrative centers in the spinal cord and brainstem and on to the brain, where it undergoes higher sensory and cognitive analysis, allowing the body to respond appropriately to the stimuli. While the experience of pain may be considered to be unpleasant, it is a useful tool in communicating to us and to others that there is something wrong with our bodies. Ultimately, these responses help restrict further damage to the body and start the process of healing.
In a clinical setting, the ability to communicate about pain allows an individual to seek strategies to ease the pain, such as taking analgesics. Being unable to effectively communicate one's experience of pain leaves the individual vulnerable to prolonged suffering. One such vulnerable group is infants.
Ignored and untreated pain in infants has been shown to have immediate and long-term effects as a result of structural and physiological changes within the nervous system. For example, the body responds to untreated pain by increased release of stress hormones, which may be associated with increased morbidity and mortality in the short term. Long-term effects of pain may include altered pain perception, chronic pain syndromes, and somatic complaints such as sleep disturbances, feeding problems, and inability to self-regulate in response to internal and external stressors. It has been proposed that attention deficit disorders, learning disorders, and behavioral problems in later childhood may be linked to repetitive pain in the preterm infant.
Why Was This Study Done?
Until as recently as the 1990s, newborns in some clinical centres underwent surgery with minimal anesthesia. Also, newborns received little or no pain management postoperatively or for painful procedures such as lumbar punctures or circumcisions. Since then, there has been growing awareness amongst clinicians that pain may be experienced from the earliest stages of postnatal life and that inadequate analgesia may lead to the type of long-term consequences mentioned above. However, gauging how much pain infants and young children are experiencing remains a substantial challenge. The researchers in this study wanted to assess the association between cortical pain responses in young infants and currently used tools for the assessment of pain in these infants. These current tools are based on behavioral and physiological measures, such as change in facial expression, and it is possible that these tools do not give an adequate measure of pain especially in infants born preterm.
What Did the Researchers Do and Find?
Twelve clinically stable infants were studied on 33 occasions when they required a heel lance to obtain a blood sample for a clinical reason. The researchers examined the relationship between brain activity and a clinical pain score, calculated using the premature infant pain profile (PIPP) in response to a painful event. Activity in the somatosensory cortex was measured noninvasively by near-infrared spectroscopy, which measures brain regional changes in oxygenated and deoxygenated hemoglobin concentration. The PIPP is a well-established pain score that ascribes a value to infant behavior such as change in facial expression.
They found that changes in brain activity in response to a painful stimulus were related to the PIPP scores. These changes were more strongly linked to the behavioral components of the PIPP, e.g., facial expression, than physiological components, e.g., heart rate. They also found that a positive brain response could occur in the absence of any facial expression.
What Do These Findings Mean?
Behaviors to communicate pain require motor responses to sensory and emotional stimuli. The maturity of this complex system in infants is not clearly understood. The results of this study raise further awareness of the ability of infants to experience pain and highlight the possibility that pain assessment based on behavioral tools alone may underestimate the pain response in infants.
Additional Information.
Please access these Web sites via the online version of this summary at
Important papers on pain in human neonates are discussed in the open access Paediatric Pain Letter with links to original articles
The Institute of Child Health in London has a Web site describing a three-year international project on improving the assessment of pain in hospitalized children, with many useful links
The International Association for the Study of Pain (IASP) provides accurate and up-to-date information and links about pain mechanisms and treatment
PMCID: PMC2504041  PMID: 18578562
6.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
PMCID: PMC2661253  PMID: 19360087
7.  Fibromyalgia interacts with age to change the brain☆☆☆ 
NeuroImage : Clinical  2013;3:249-260.
Although brain plasticity in the form of gray matter increases and decreases has been observed in chronic pain, factors determining the patterns of directionality are largely unknown. Here we tested the hypothesis that fibromyalgia interacts with age to produce distinct patterns of gray matter differences, specifically increases in younger and decreases in older patients, when compared to age-matched healthy controls. The relative contribution of pain duration was also investigated. Regional gray matter was measured in younger (n = 14, mean age 43, range 29–49) and older (n = 14; mean age 55, range 51–60) female fibromyalgia patients and matched controls using voxel-based morphometry and cortical thickness analysis of T1-weighted magnetic resonance images. To examine their functional significance, gray matter differences were compared with experimental pain sensitivity. Diffusion-tensor imaging was used to assess whether white matter changed in parallel with gray matter, and resting-state fMRI was acquired to examine whether pain-related gray matter changes are associated with altered functional connectivity. Older patients showed exclusively decreased gray matter, accompanied by compromised white matter integrity. In contrast, younger patients showed exclusively gray matter increases, namely in the basal ganglia and insula, which were independent of pain duration. Associated white matter changes in younger patients were compatible with gray matter hypertrophy. In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients. Whereas more pronounced gray matter decreases in the posterior cingulate cortex were related to increased experimental pain sensitivity in older patients, insular gray matter increases in younger patients correlated with lower pain sensitivity, possibly indicating the recruitment of endogenous pain modulatory mechanisms. This is supported by the finding that the insula in younger patients showed functional decoupling from an important pain-processing region, the dorsal anterior cingulate cortex. These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications.
PMCID: PMC3814958  PMID: 24273710
VBM, voxel-based morphometry; CTA, cortical thickness analysis; FA, fractional anisotropy; aINS, anterior insula; NAc, nucleus accumbens; ACC, anterior cingulate cortex; PCC, posterior cingulate cortex; MPFC, medial prefrontal cortex; DLPFC, dorsolateral prefrontal cortex; PMC, premotor cortex; Chronic pain; Age; MRI; Insula; Cingulate; VBM
8.  Major Depressive Disorder is Associated with Altered Functional Brain Response During Anticipation and Processing of Heat Pain 
Archives of general psychiatry  2008;65(11):1275-1284.
Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD).
To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD.
Functional magnetic resonance neuroimaging (fMRI) data were collected during an event-related factorial experimental pain paradigm. Painful and non-painful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus.
University brain imaging center.
15 (12 F) young adults with current MDD and 15 (10F) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a board-certified psychiatrist.
Main Outcome measure
Between-group differences in blood oxygen level-dependent fMRI signal change to anticipation and processing of painful versus non-painful temperature stimuli.
MDD compared to healthy controls showed: (1) increased activation in right anterior insular region, dorsal anterior cingulate and right amygdala during anticipation of painful relative to non-painful stimuli, (2) increased activation in right amygdala and decreased activation in periaqueductal gray, rostral anterior cingulate and prefrontal cortices during painful stimulation relative to non-painful stimulation, and (3) in MDD subjects greater activation in the right amygdala during anticipation of pain was associated with greater levels of perceived helplessness.
These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects ability to modulate negative affective states in MDD, which is a core characteristic of this disorder.
PMCID: PMC2702160  PMID: 18981339
9.  Neonatal pain: What's age got to do with it? 
Surgical Neurology International  2014;5(Suppl 13):S479-S489.
The neurobiology of neonatal pain processing, especially in preterm infants, differs significantly from older infants, children, adolescence, and adults. Research suggests that strong painful procedures or repeated mild procedures may permanently modify individual pain processing. Acute injuries at critical developmental periods are risk factors for persistent altered neurodevelopment. The purpose of this narrative review is to present the seminal and current literature describing the unique physiological aspects of neonatal pain processing.
Articles describing the structures and physiological processes that influence neonatal pain were identified from electronic databases Medline, PubMed, and CINAHL.
The representation of neonatal pain physiology is described in three processes: Local peripheral nervous system processes, referred to as transduction; spinal cord processing, referred to as transmission and modulation; and supraspinal processing and integration or perception of pain. The consequences of undermanaged pain in preterm infants and neonates are discussed.
Although the process and pain responses in neonates bear some similarity to processes and pain responses in older infants, children, adolescence, and adults; there are some pain processes and responses that are unique to neonates rendering them at risk for inadequate pain treatment. Moreover, exposure to repeated painful stimuli contributes to adverse long-term physiologic and behavioral sequelae. With the emergence of studies showing that painful experiences are capable of rewiring the adult brain, it is imperative that we treat neonatal pain effectively.
PMCID: PMC4253046  PMID: 25506507
Neonate; neurodevelopment; pain; preterm infant; pain processing
10.  Nonsurgical Treatment of Lumbar Disk Herniation: Are Outcomes Different in Older Adults? 
To determine whether older adults (age≥60 years) experience less improvement in disability and pain with nonsurgical treatment of lumbar disk herniation (LDH), as compared to younger adults (age<60 years).
Prospective longitudinal comparative cohort study.
Outpatient specialty spine clinic
133 consecutive patients with radicular pain and MR-confirmed acute LDH (89 younger adults and 44 older adults).
Nonsurgical treatment tailored to the individual patient.
Patient-reported disability on the Oswestry Disability Index (ODI), leg pain intensity, and back pain intensity were recorded at baseline, 1, 3, and 6 months. The primary outcome was the ODI change score at 6 months. Secondary longitudinal analyses examined rates of change over the follow-up period.
Older adults demonstrated improvements in ODI(range 0-100) and pain intensity(range 0-10) with nonsurgical treatment that were not significantly different from those seen in younger adults at 6 month follow-up, either with or without adjustment for potential confounders. Adjusted mean improvements in older adults as compared to younger adults were 31 vs. 33 (p=0.63) for ODI, 4.5 vs. 4.5 (p=0.99) for leg pain, and 2.4 vs. 2.7 for back pain (p=0.69). A greater amount of the total improvement in leg pain and back pain in older adults was noted in the first month of follow-up, as compared to younger adults.
These preliminary findings suggest that the outcomes of LDH with nonsurgical treatment were not worse in older adults (age≥60 years) as compared to younger adults (age<60 years). Future research is warranted to examine nonsurgical treatment for LDH in older adults.
PMCID: PMC3102576  PMID: 21391933
herniation; Iitervertebral disk displacement; geriatrics; outcomes
11.  Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study 
PLoS ONE  2014;9(2):e90185.
Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency.
Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively.
Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001).
Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition.
PMCID: PMC3935997  PMID: 24587268
12.  Impact of Chronic Musculoskeletal Pathology on Older Adults: A Study of Differences between Knee OA and Low Back Pain 
Pain medicine (Malden, Mass.)  2009;10(4):693-701.
The study aimed to compare the psychological and physical characteristics of older adults with knee osteoarthritis (OA) vs those of adults with chronic low back pain (CLBP) and to identify psychological and physical predictors of function as measured by gait speed.
Secondary data analysis.
Method and Patients
Eighty-eight older adults with advanced knee OA and 200 with CLBP who had participated in separate randomized controlled trials were selected for this study.
Inclusion criteria for both trials included age ≥65 and pain of at least moderate intensity that occurred daily or almost every day for at least the previous 3 months. Psychological constructs (catastrophizing, fear avoidance, self-efficacy, depression, affective distress) and physical measures (comorbid medical conditions, pain duration, pain severity, pain related interference, self-rated health) were obtained.
Subjects with CLBP had slower gait (0.88 m/s vs 0.96 m/s, P = 0.002) and more comorbid conditions than subjects with knee pain (mean 3.36 vs 1.97, P < 0.001). All the psychological measures were significantly worse in the CLBP group except the Multidimensional Pain Inventory–Affective Distress score. Self-efficacy, pain severity, and medical comorbidity burden were associated with slower gait regardless of the location of the pain.
Older adults with chronic pain may have distinct psychological and physical profiles that differentially impact gait speed. These findings suggest that not all pain conditions are the same in their psychological and physical characteristics and may need to be taken into consideration when developing treatment plans.
PMCID: PMC2836854  PMID: 19254337
Low Back Pain; Knee Pain; Physical Function; Psychosocial Factors
13.  Symptom Burden of Adults with Type 2 Diabetes Across the Disease Course: Diabetes & Aging Study 
Journal of General Internal Medicine  2012;27(12):1674-1681.
Reducing symptom burden is paramount at the end-of-life, but typically considered secondary to risk factor control in chronic disease, such as diabetes. Little is known about the symptom burden experienced by adults with type 2 diabetes and the need for symptom palliation.
To examine pain and non-pain symptoms of adults with type 2 diabetes over the disease course – at varying time points before death and by age.
Survey follow-up study.
13,171 adults with type 2 diabetes, aged 30–75 years, from Kaiser Permanente, Northern California, who answered a baseline symptom survey in 2005–2006.
Pain and non-pain symptoms were identified by self-report and medical record data. Survival status from baseline was categorized into ≤6, >6–24, or alive >24 months.
Mean age was 60 years; 48 % were women, and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 % insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent in all survival status categories, but was more prevalent among those with shorter survival, p < .001. Adults ≥60 years who were alive >24 months reported more physical symptoms such as acute pain and dyspnea, whereas participants <60 years reported more psychosocial symptoms, such as depressed mood and insomnia. Adjustment for duration of diabetes and comorbidity reduced the association between age and pain, but did not otherwise change our results.
In a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. Older adults reported more physical symptoms, whereas younger adults reported more psychosocial symptoms. Diabetes care management should include not only good cardiometabolic control, but also symptom palliation across the disease course.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2132-3) contains supplementary material, which is available to authorized users.
PMCID: PMC3509316  PMID: 22854982
palliative care; diabetes mellitus type 2; quality of life
14.  Multisystem Dysregulation in Painful Temporomandibular Disorders 
Multiple physiological and psychological regulatory domains may contribute to the pathophysiology of pain in temporomandibular disorder (TMD) and other bodily pain conditions. The purpose of this study was to evaluate the relationship between multisystem dysregulation and the presence of TMD pain, as well as the presence of different numbers of comorbid pain conditions in TMD. Secondary data analysis was conducted in 131 non-TMD (without comorbid pain) controls, 14 TMD subjects without comorbid pain, 78 TMD subjects with 1 comorbid pain, and 67 TMD subjects with multiple comorbid pain conditions who participated in a TMD genetic study. Twenty markers from sensory, autonomic, inflammatory, and psychological domains were evaluated. The results revealed that 1) overall dysregulation in multiple system domains (OR [odds ratio] = 1.6, 95% confidence interval [CI] = 1.4–1.8), particularly in the sensory (OR = 1.9, 95% CI = 1.3–2.9) and the psychological (OR = 2.1, 95% CI = 2.1–2.7) domains, were associated with increased likelihood of being a painful TMD case; and 2) dysregulations in individual system domains were selectively associated with the increased odds of being a TMD case with different levels of comorbid persistent pain conditions. These outcomes indicate that heterogeneous multisystem dysregulations may exist in painful TMD subgroups, and multidimensional physiological and psychological assessments can provide important information regarding pathophysiology, diagnosis, and management of pain in TMD patients.
The concurrent assessment of multiple physiological and psychological systems is critical to our understanding of the pathophysiological processes that contribute to painful TMD and associated comorbid conditions, which will ultimately guide and inform appropriate treatment strategies that address the multisystem dysregulation associated with complex and common persistent pain conditions.
PMCID: PMC3770463  PMID: 23721875
Temporomandibular disorders; multisystem dysregulation; comorbid pain conditions; headache
15.  Functional outcome in older adults with joint pain and comorbidity: design of a prospective cohort study 
Joint pain is a highly prevalent condition in the older population. Only a minority of the older adults consult the general practitioner for joint pain, and during consultation joint pain is often poorly recognized and treated, especially when other co-existing chronic conditions are involved. Therefore, older adults with joint pain and comorbidity may have a higher risk of poor functional outcome and decreased quality of life (QoL), and possibly need more attention in primary care. The main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The study will also identify predictors of decreased QoL. The results will be used to develop prediction models for the early identification of subgroups at high risk of poor functional outcome and decreased QoL. This may contribute to better targeting of treatment and to more effective health care in this population.
The study has been designed as a prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. For the recruitment of 450 patients, 25 general practices will be approached. Patients are eligible for participation if they are 65 years or older, have at least two chronic conditions and report joint pain on most days. Data will be collected using various methods (i.e. questionnaires, physical tests, patient interviews and focus groups). We will measure different aspects of functioning (e.g. mobility, functional independence and participation) and QoL. Other measurements concern possible predictors of functioning and QoL (e.g. pain, co-existing chronic conditions, markers for frailty, physical performance, psychological factors, environmental factors and individual factors). Furthermore, health care utilization, health care needs and the meaning and impact of joint pain will be investigated from an older person's perspective.
In this paper, we describe the protocol of a prospective cohort study in Dutch older adults with joint pain and comorbidity and discuss the potential strengths and limitations of the study.
PMCID: PMC3214164  PMID: 22024146
16.  Prediction of Postoperative Pain using Path Analysis in Older Patients 
Journal of anesthesia  2011;26(1):1-8.
Effective postoperative pain management is important for older surgical patients since pain affects perioperative outcomes. A prospective cohort study was conducted to describe the direct and indirect effects of patient risk factors and pain treatment in explaining levels of postoperative pain in older surgical patients.
We studied patients who were 65 years of age or older and were scheduled for major non-cardiac surgery with a postoperative hospital stay of at least 2 days. The numeric rating scale (0 = no pain, 10 = worst possible pain) was used to measure pain levels before surgery and once daily for 2 days after surgery. Path analysis was performed to examine the association between predictive variables and postoperative pain levels.
Three hundred fifty patients were studied. The results reveal that preoperative pain level, use of preoperative opioids, female gender, higher ASA physical status, and postoperative pain control methods were the strongest predictors of postoperative pain as measured the first day after surgery. Younger age, greater preoperative symptoms of depression and lower cognitive function also contributed to higher postoperative pain levels. Pain levels on the second day after surgery were strongly predicted by preoperative pain level, use of preoperative opioids, surgical risk, and pain and opioid dose on postoperative day 1. However, younger age, female gender, higher ASA physical status, greater preoperative symptoms of depression, lower cognitive function and postoperative pain control methods indirectly contributed to pain levels on the second day after surgery.
Although preoperative pain and use of preoperative opioids have the strongest effects on postoperative pain, clinicians should be aware that other factors such as age, gender, surgical risk, preoperative cognitive impairment and depression also contribute to reported postoperative pain. Based on significant statistical correlations, these study results can contribute to more effective postoperative care for those patients having the risk factors studied here. Preoperative treatment/intervention based in part on factors such as preoperative pain, use of preoperative opioids and depression may improve postoperative pain management.
PMCID: PMC3720127  PMID: 22012171
aged; 80 and over; aging; pain; postoperative
17.  Gray matter alterations in chronic pain: A network-oriented meta-analytic approach 
NeuroImage : Clinical  2014;4:676-686.
Several studies have attempted to characterize morphological brain changes due to chronic pain. Although it has repeatedly been suggested that longstanding pain induces gray matter modifications, there is still some controversy surrounding the direction of the change (increase or decrease in gray matter) and the role of psychological and psychiatric comorbidities. In this study, we propose a novel, network-oriented, meta-analytic approach to characterize morphological changes in chronic pain. We used network decomposition to investigate whether different kinds of chronic pain are associated with a common or specific set of altered networks. Representational similarity techniques, network decomposition and model-based clustering were employed: i) to verify the presence of a core set of brain areas commonly modified by chronic pain; ii) to investigate the involvement of these areas in a large-scale network perspective; iii) to study the relationship between altered networks and; iv) to find out whether chronic pain targets clusters of areas. Our results showed that chronic pain causes both core and pathology-specific gray matter alterations in large-scale networks. Common alterations were observed in the prefrontal regions, in the anterior insula, cingulate cortex, basal ganglia, thalamus, periaqueductal gray, post- and pre-central gyri and inferior parietal lobule. We observed that the salience and attentional networks were targeted in a very similar way by different chronic pain pathologies. Conversely, alterations in the sensorimotor and attention circuits were differentially targeted by chronic pain pathologies. Moreover, model-based clustering revealed that chronic pain, in line with some neurodegenerative diseases, selectively targets some large-scale brain networks. Altogether these findings indicate that chronic pain can be better conceived and studied in a network perspective.
•Chronic pain causes both core and pathology-specific.•GM alterations in brain networks.•Model-based clustering revealed that chronic pain selectively targets brain networks.•Chronic pain can be better conceived and studied in a network perspective.
PMCID: PMC4053643  PMID: 24936419
Chronic pain; Brain networks; Gray matter alterations; Voxel-Based Metaanalysis
18.  Serious Psychological Distress in U.S. Adults with Arthritis 
Journal of General Internal Medicine  2006;21(11):1160-1166.
Arthritis and mental health disorders are leading causes of disability commonly seen by health care providers. Several studies demonstrate a higher prevalence of anxiety and depression in persons with arthritis versus those without arthritis.
Determine the national prevalence of serious psychological distress (SPD) and frequent anxiety or depression (FAD) in adults with arthritis, and in adults with arthritis, identify risk factors associated with SPD.
Cross-sectional data from the 2002 National Health Interview Survey, an in-person household interview survey, were used to estimate the prevalence of SPD and FAD in adults with (n =6,829) and without (n =20,676) arthritis. In adults with arthritis, the association between SPD and sociodemographic, clinical, and functional factors was evaluated using multivariable logistic regression.
The prevalence of SPD and FAD in adults with arthritis is significantly higher than in adults without arthritis (5.6% vs 1.8% and 26.2% vs 10.7%, P <.001, respectively). In adults with arthritis, SPD was significantly associated with younger age, lower socioeconomic status, divorce/separation, recurrent pain, physical inactivity, having functional or social limitations, and having comorbid medical conditions. Adults aged 18 to 44 years were 6.5 times more likely to report SPD than those 65 years or older, and adults with recurrent pain were 3 times more likely to report SPD than those without recurrent pain.
Serious psychological distress and FAD affect persons with arthritis and should be addressed in their treatment. Younger adults with arthritis, and those with recurrent pain or either functional or social limitations, may be at higher risk for SPD.
PMCID: PMC1831669  PMID: 16879706
arthritis; mental health; depression; anxiety; psychological distress
19.  Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury 
PLoS ONE  2014;9(9):e109099.
In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain following SCI and to identify potential therapeutic targets for the treatment of chronic pathological pain.
PMCID: PMC4182513  PMID: 25268642
20.  Chronic shoulder pain in the community: a syndrome of disability or distress? 
Annals of the Rheumatic Diseases  2002;61(2):128-131.
Objectives: To investigate two questions in a community based population of people with chronic shoulder pain. Firstly, does chronic pain lead to impaired psychological health over time? Secondly, how does restriction of daily activity influence pain perception and psychological health?
Methods: Two postal surveys, two years apart, were carried out to identify a group of subjects with chronic shoulder pain. The first survey was sent to a random sample of adults (n=40026) registered with a primary care practice, and included a pain manikin, demographic information, and the Hospital Anxiety and Depression scale (HAD). The second survey was sent to those subjects who reported unilateral shoulder region pain in the first survey and it included a shoulder-specific disability scale, pain severity score, and the HAD.
Results: 2606 (65.1%) people responded to the initial survey. Of these, 304 (11.7%) reported unilateral shoulder region pain at baseline. In the subsequent survey, there were 234 responders (83.3% adjusted response): 142 of these reported shoulder pain and formed our study group of "subjects with chronic shoulder pain". Within this group there was no significant change in psychological distress scores between baseline and follow up. Both the disability score and psychological distress scores correlated significantly with pain severity (disability v pain r=0.536, p<0.001; psychological distress v pain r=0.269, p=0.002). When the correlation between disability and pain severity was corrected for possible confounders, it remained significant (r=0.490, p<0.001). This was not the case for the correlation between psychological distress and pain (p>0.05). Disability was significantly correlated with psychological distress on univariate (r=0.445, p<0.001) and multivariate analysis (r=0.341, p=0.002).
Conclusion: In those with chronic shoulder pain the relation between pain and psychological health seems to be linked to disability. Psychological distress was not explained by persistent pain itself.
PMCID: PMC1754001  PMID: 11796398
21.  Psychological therapies for the management of chronic and recurrent pain in children and adolescents 
Chronic pain affects many children, who report severe pain, distressed mood, and disability. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update adds recently published randomised controlled trials (RCTs) to the review published in 2009.
To assess the effectiveness of psychological therapies, principally cognitive behavioural therapy and behavioural therapy, for reducing pain, disability, and improving mood in children and adolescents with recurrent, episodic, or persistent pain. We also assessed the risk of bias and methodological quality of the included studies.
Search methods
Searches were undertaken of MEDLINE, EMBASE, and PsycLIT. We searched for RCTs in references of all identified studies, meta-analyses and reviews. Date of most recent search: March 2012.
Selection criteria
RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment were eligible for inclusion (waiting list or standard medical care) for children or adolescents with episodic, recurrent or persistent pain.
Data collection and analysis
All included studies were analysed and the quality of the studies recorded. All treatments were combined into one class: psychological treatments; headache and non-headache outcomes were separately analysed on three outcomes: pain, disability, and mood. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (at least three months after the post-treatment assessment point, but not more than 12 months).
Main results
Eight studies were added in this update of the review, giving a total of 37 studies. The total number of participants completing treatments was 1938. Twenty-one studies addressed treatments for headache (including migraine); seven for abdominal pain; four included mixed pain conditions including headache pain, two for fibromyalgia, two for pain associated with sickle cell disease, and one for juvenile idiopathic arthritis. Analyses revealed five significant effects. Pain was found to improve for headache and non-headache groups at post-treatment, and for the headache group at follow-up. Mood significantly improved for the headache group at follow-up, although, this should be interpreted with caution as there were only two small studies entered into the analysis. Finally, disability significantly improved in the non-headache group at post-treatment. There were no other significant effects.
Authors’ conclusions
Psychological treatments are effective in reducing pain intensity for children and adolescents (<18 years) with headache and benefits from therapy appear to be maintained. Psychological treatments also improve pain and disability for children with non-headache pain. There is limited evidence available to estimate the effects of psychological therapies on mood for children and adolescents with headache and non-headache pain. There is also limited evidence to estimate the effects on disability in children with headache. These conclusions replicate and add to those of the previous review which found psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up.
PMCID: PMC3715398  PMID: 23235601
*Pain Management; Abdominal Pain [therapy]; Chronic Disease; Cognitive Therapy; Fibromyalgia [therapy]; Headache [therapy]; Hemoglobin SC Disease [complications]; Mood Disorders [therapy]; Pain [psychology]; Psychotherapy [*methods]; Randomized Controlled Trials as Topic; Recurrence; Adolescent; Child; Humans
22.  Pain characteristics of adults 65 years of age and older referred to a tertiary care pain clinic 
Reports indicate that characteristics of older adults with chronic pain may be different than those of younger persons.
To study the pain characteristics of older patients presenting to a tertiary pain clinic for the first time.
Age, sex and relative contributions of biomedical versus psychosocial variables contributing to chronic pain were investigated in patients 65 years of age and older, in comparison with younger patients, from a sample of 1242 consecutive new patients attending a tertiary care pain clinic. The presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision somatoform pain disorders were defined, using an explicated method of ascertaining the biomedical and psychological variables underlying the pain complaints.
The older patients (14.7% of the total sample) had relatively more physical problems (concordant with their complaints) but fewer psychological factors contributing to disability than the younger pain patients. Musculoskeletal and neuropathic disorders affected 40.7% and 35.2% of the older patients, respectively, while several patients had more than one painful disorder. Musculoskeletal problems were more prevalent in the women, and neuropathic problems were more prevalent in the men.
The older pain patients are a distinct group. Factors affecting the delayed presentation of older pain patients to the pain clinic and limitations of the present study are discussed.
PMCID: PMC2799262  PMID: 18958310
Chronic pain; Older adults; Pain disorder
23.  Forebrain Pain Mechanisms 
Brain research reviews  2008;60(1):226-242.
Emotional-affective and cognitive dimensions of pain are less well understood than nociceptive and nocifensive components, but the forebrain is believed to play an important role. Recent evidence suggests subcortical and cortical brain areas outside the traditional pain processing network contribute critically to emotional-affective responses and cognitive deficits related to pain. These brain areas include different nuclei of the amygdala and certain prefrontal cortical areas. Their roles in various aspects of pain will be discussed. Biomarkers of cortical dysfunction are being identified that may evolve into therapeutic targets to modulate pain experience and improve pain-related cognitive impairment. Supporting data from preclinical studies in neuropathic pain models will be presented. Neuroimaging analysis provides evidence for plastic changes in the pain processing brain network. Results of clinical studies in neuropathic pain patients suggest that neuroimaging may help determine mechanisms of altered brain functions in pain as well as monitor the effects of pharmacologic interventions to optimize treatment in individual patients. Recent progress in the analysis of higher brain functions emphasizes the concept of pain as a multidimensional experience and the need for integrative approaches to determine the full spectrum of harmful or protective neurobiological changes in pain.
PMCID: PMC2700838  PMID: 19162070
Pain; emotion; cognition; decision-making; amygdala; prefrontal cortex
24.  A descriptive study of older adults with persistent pain: Use and perceived effectiveness of pain management strategies [ISRCTN11899548] 
BMC Geriatrics  2005;5:12.
Persistent pain is a common, often debilitating, problem in older adults; however, few studies have focused on the experiences of older adults in managing their pain. The objective of this study was to describe the use and perceived effectiveness of pain management strategies in a sample of older adults and to explore the associations of these variables with demographic and psychosocial characteristics.
Adults ≥ 65 years old and living in retirement facilities who reported persistent pain (N = 235, mean age = 82 years, 84% female, 94% white) completed measures of demographics, pain, depression, self-efficacy for managing pain, and a Pain Management Strategies Survey. Participants identified current and previous-year use of 42 pain management strategies and rated helpfulness of each on a 5-point scale.
Acetaminophen, regular exercise, prayer, and heat and cold were the most frequently used pain management strategies (61%, 58%, 53%, and 48%, respectively). Strategies used by >25% of the sample that were rated moderately or more helpful (i.e., >2 on a 0 to 4 scale) were prayer [mean (SD) = 2.9 (0.9)], opioids [2.6 (0.8)], regular exercise [2.5 (1.0)], heat/cold [2.5 (1.0)], nonsteroidal anti-inflammatory drugs [2.4 (1.0)], and acetaminophen [2.3 (1.0)]. Young-old (65–74 years) study participants reported use of more strategies than did old-old (85+ years) participants (p = .03). Perceived helpfulness of strategy use was significantly associated with pain intensity (r = -.14, p < .0001), self-efficacy (r = .28, p < .0001), and depression (r = -.20, p = .003).
On average, older adults view the strategies they use for persistent pain as only moderately helpful. The associations between perceived helpfulness and self-efficacy and depression suggest avenues of pain management that are focused less on specific treatments and more on how persons with persistent pain think about their pain.
PMCID: PMC1298294  PMID: 16277666
25.  Self-injurious behaviour in intellectual disability syndromes: evidence for aberrant pain signalling as a contributing factor 
In most individuals, injury results in activation of peripheral nociceptors (pain-sensing neurons of the peripheral nervous system) and amplification of central nervous system (CNS) pain pathways that serve as a disincentive to continue harmful behaviour; however, this may not be the case in some developmental disorders that cause intellectual disability (ID). Moreover, individuals affected by ID disorders may initiate self-injurious behaviour to address irritating or painful sensations. In normal individuals, a negative feedback loop decreases sensation of pain, which involves descending inhibitory neurons in the CNS that attenuate spinal nociceptive processing. If spinal nociceptive signalling is impaired in these developmental disorders, an exaggerated painful stimulus may be required in order to engage descending anti-nociceptive signals.
Using electronic databases, we conducted a review of publications regarding the incidence of chronic pain or altered pain sensation in ID patients or corresponding preclinical models.
There is a body of evidence indicating that individuals with fragile X mental retardation and/or Rett syndrome have altered pain sensation. These findings in humans are supported by mechanistic studies using genetically modified mice harbouring mutations consistent with the human disease. Thus, once self-injurious behaviour is initiated, the signal to stop may be missing. Several developmental disorders that cause ID are associated with increased incidence of gastroesophageal reflux disease (GERD), which can cause severe visceral pain. Individuals affected by these disorders who also have GERD may self-injure as a mechanism to engage descending inhibitory circuits to quell visceral pain. In keeping with this hypothesis, pharmacological treatment of GERD has been shown to be effective for reducing self-injurious behaviour in some patients. Hence, multiple lines of evidence suggest aberrant nociceptive processing in developmental disorders that cause ID.
There is evidence that pain pathways and pain amplification mechanisms are altered in several preclinical models of developmental disorders that cause ID. We present hypotheses regarding how impaired pain pathways or chronic pain might contribute to self-injurious behaviour. Studies evaluating the relationship between pain and self-injurious behaviour will provide better understanding of the mechanisms underlying self-injurious behaviour in the ID population and may lead to more effective treatments.
PMCID: PMC3272540  PMID: 21917053
central sensitization; diffuse noxious inhibitory control; fragile X; pain; Rett syndrome; self-injury

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