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1.  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
2.  Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device 
BMC Neuroscience  2010;11:142.
Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature.
A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex.
A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non-invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation.
The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents [1] and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) [2]. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood [3-5]. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) [6,7], is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology [8-10], but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" [7].
Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain [11]. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.
In the past few years several studies used fMRI to investigate the human trigeminal system [12,13], with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation [14] or only teeth [15-17]. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner [17,18]: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli [19], as reliability/reproducibility is a necessary feature of sensory testing [20].
Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.
PMCID: PMC2988799  PMID: 21029454
3.  Psychiatric diagnoses in patients with burning mouth syndrome and atypical odontalgia referred from psychiatric to dental facilities 
Burning mouth syndrome (BMS) and atypical odontalgia (AO) are two conditions involving chronic oral pain in the absence of any organic cause. Psychiatrically they can both be considered as “somatoform disorder”. From the dental point of view, however, the two disorders are quite distinct. BMS is a burning or stinging sensation in the mouth in association with a normal mucosa whereas AO is most frequently associated with a continuous pain in the teeth or in a tooth socket after extraction in the absence of any identifiable cause. Because of the absence of organic causes, BMS and AO are often regarded as psychogenic conditions, although the relationship between oral pain and psychologic factors is still unclear. Some studies have analyzed the psychiatric diagnoses of patients with chronic oral pain who have been referred from dental facilities to psychiatric facilities. No study to date has investigated patients referred from psychiatric facilities to dental facilities.
To analyze the psychiatric diagnoses of chronic oral pain patients, diagnosed with BMS and AO, and referred from psychiatric facilities to dental facilities.
Study design
Psychiatric diagnoses and disease conditions of BMS or AO were investigated in 162 patients by reviewing patients’ medical records and referral forms. Psychiatric diagnoses were categorized according to the International Statistical Classification of Disease and Related Health Problems, Tenth Revision.
The proportion of F4 classification (neurotic, stress-related, and somatoform disorders) in AO patients was significantly higher than in BMS patients. BMS patients were more frequently given a F3 classification (mood/affective disorders). However, 50.8% of BMS patients and 33.3% of AO patients had no specific psychiatric diagnoses.
Although BMS and AO are both chronic pain disorders occurring in the absence of any organic cause, the psychiatric diagnoses of patients with BMS and AO differ substantially.
PMCID: PMC2987502  PMID: 21127687
glossodynia; stomatodynia; ICD-10; somatoform disorder
4.  Spinal Cord Stimulation for Neuropathic Pain 
Executive Summary
The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology.
Clinical Need
SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage.
The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada.
Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain.
Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS.
The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable pain of postherpetic neuralgia, which is a persistent burning pain and hyperesthesia along the distribution of a cutaneous nerve after an attack of herpes zoster, is also managed with SCS.
For each condition, SCS is considered as a pain management therapy only after conventional pain therapies, including pharmacological, nonpharmacological, and surgical treatments, if applicable, have been attempted and have failed.
The Technology
The SCS technology consists of 3 implantable components: a pulse generator, an extension cable, and a lead (a small wire). The pulse generator is the power source for the spinal cord stimulator. It generates low-voltage electrical pulses. The extension cable connects the pulse generator to the lead. The lead is a small, insulated wire that has a set of electrodes at one end. The lead is placed into the epidural space on the posterior aspect of the spinal cord, and the electrodes are positioned at the level of the nerve roots innervating the painful area. An electrical current from the electrodes induces a paresthesia, or a tingling sensation that masks the pain.
Before SCS is initiated, candidates must have psychological testing to rule out major psychological illness, drug habituation, and issues of secondary gain that can negatively influence the success of the therapy. Successful candidates will have a SCS test stimulation period (trial period) to assess their responsiveness to SCS. The test stimulation takes about 1 week to complete, and candidates who obtain at least 50% pain relief during this period are deemed suitable to receive a permanent implantation of a spinal cord stimulator
Review Strategy
The Medical Advisory Secretariat (MAS) reviewed all published health technology assessments of spinal cord stimulation. Following this, a literature search was conducted from 2000 to January, 2005 and a systematic review of the literature was completed. The primary outcome for the systematic review was pain relief. Secondary outcomes included functional status and quality of life. After applying the predetermined inclusion and exclusion criteria, 2 randomized controlled trials (MAS level 2 evidence), and 2 prospective non-randomized controlled trials with a before-and-after-treatment study design (MAS level 3a evidence) were retrieved and reviewed.
Summary of Findings
The authors of 6 health technology assessments concluded that evidence exists to support the effectiveness of SCS to decrease pain in various neuropathic pain syndromes. However, the quality of this evidence varied among reports from weak to moderate.
The systematic review completed by MAS found high quality level 2 evidence that SCS decreases pain and level 3a evidence that it improves functional status and quality of life in some people with neuropathic pain conditions. The rate of technical failures was approximately 11%, which included electrode lead migration and/or malposition. Procedural complications included infection and dural puncture; each occurred at a rate of 1.2%.
SCS may be considered for patients with chronic, neuropathic pain for whom standard pain treatments have failed and when there is no indication for surgical intervention to treat the underlying condition.
PMCID: PMC3382299  PMID: 23074473
5.  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
6.  Chronic Neck Pain: Making the Connection Between Capsular Ligament Laxity and Cervical Instability 
The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain.
The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome.
When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability.
Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability.
PMCID: PMC4200875  PMID: 25328557
Atlanto-axial joint; Barré- Liéou syndrome; C1-C2 facet joint; capsular ligament laxity; cervical instability; cervical radiculopathy; chronic neck pain; facet joints; post-concussion syndrome; prolotherapy; spondylosis; vertebrobasilar insufficiency; whiplash.
7.  Current algorithm for the surgical treatment of facial pain 
Head & Face Medicine  2007;3:30.
Facial pain may be divided into several distinct categories, each requiring a specific treatment approach. In some cases, however, such categorization is difficult and treatment is ineffective. We reviewed our extensive clinical experience and designed an algorithmic approach to the treatment of medically intractable facial pain that can be treated through surgical intervention.
Our treatment algorithm is based on taking into account underlying pathological processes, the anatomical distribution of pain, pain characteristics, the patient's age and medical condition, associated medical problems, the history of previous surgical interventions, and, in some cases, the results of psychological evaluation. The treatment modalities involved in this algorithm include diagnostic blocks, peripheral denervation procedures, craniotomy for microvascular decompression of cranial nerves, percutaneous rhizotomies using radiofrequency ablation, glycerol injection, balloon compression, peripheral nerve stimulation procedures, stereotactic radiosurgery, percutaneous trigeminal tractotomy, and motor cortex stimulation. We recommend that some patients not receive surgery at all, but rather be referred for other medical or psychological treatment.
Our algorithmic approach was used in more than 100 consecutive patients with medically intractable facial pain. Clinical evaluations and diagnostic workups were followed in each case by the systematic choice of the appropriate intervention. The algorithm has proved easy to follow, and the recommendations include the identification of the optimal surgery for each patient with other options reserved for failures or recurrences. Our overall success rate in eliminating facial pain presently reaches 96%, which is higher than that observed in most clinical series reported to date
This treatment algorithm for the intractable facial pain appears to be effective for patients with a wide variety of painful conditions and may be recommended for use in other institutions.
PMCID: PMC1976607  PMID: 17651504
8.  Risk factors for onset of chronic oro-facial pain – Results of the North Cheshire oro-facial pain prospective population study 
Pain  2010;149(2):354-359.
Due to the cross-sectional nature of previous studies, whether mechanical factors predict the onset of Chronic oro-facial pain remains unclear. Aims of the current study were to test the hypotheses that self-reported mechanical factors would predict onset of Chronic oro-facial pain and that any observed relationship would be independent of the confounding effects of psychosocial factors and reporting of other unexplained symptoms. About 1735 subjects who had completed a baseline questionnaire were assessed at 2 year follow-up for the presence of Chronic oro-facial pain, psychosocial factors (anxiety and depression, illness behaviour, life stressors and reporting of somatic symptoms), mechanical dysfunction (facial trauma, grinding, phantom bite and missing teeth) and reporting of other unexplained symptoms (chronic widespread pain, irritable bowel syndrome and chronic fatigue). About 1329 subjects returned completed questionnaires (adjusted response rate 87%). About 56 (5%) reported new episodes of Chronic oro-facial pain at follow-up. Univariate analyses showed that age, gender, reporting of other unexplained symptoms, psychosocial factors and two self-report mechanical factors predicted the onset of Chronic oro-facial pain. However multivariate analysis showed that mechanical factors did not independently predict onset. The strongest predictors were health anxiety (Relative Risk (RR) 2.8, 95% CI 1.3–6.2), chronic widespread pain (RR 4.0 95% C.I. 2.2–7.4) and age (RR 0.2, 95% CI 0.1–0.7). The findings from this prospective study support the hypothesis that psychosocial factors are markers for onset of Chronic oro-facial pain. The efficacy of early psychological management of Chronic oro-facial pain to address these factors should be a priority for future investigations.
PMCID: PMC2877804  PMID: 20304556
Chronic oro-facial pain; Risk factors; General population; Psychological; Mechanical
9.  Self-Reported Facial Pain in UK Biobank Study: Prevalence and Associated Factors  
To determine the prevalence of facial pain and to examine the hypothesis that symptoms are associated with socio-demographic, dental, adverse psychological factors and pain elsewhere in the body.
Material and Methods
Cross-sectional population data were obtained from UK Biobank ( study which was conducted in 2006 - 2010 and recruited over 500,000 people.
The overall prevalence of facial pain (FP) was 1.9% (women 2.4%, men 1.2%) of which 48% was chronic. The highest prevalence was found in the 51 - 55 age group (2.2%) and the lowest in the 66 - 73 age group (1.4%). There was a difference in prevalence by ethnicity (0.8% and 2.7% in persons reporting themselves as Chinese and Mixed respectively). Prevalence of FP significantly associated with all measures of social class with the most deprived and on lowest income showing the highest prevalence (2.5% and 2.4% respectively). FP was more common in individuals who rated themselves as extremely unhappy, had history of depression and reported sleep problems. Smoking associated with increase in reporting FP while alcohol consumption had inverse association. FP associated with history of painful gums, toothache and all types of regional pain.
This is the largest ever study to provide estimates of facial pain prevalence. It demonstrates unique features (lower prevalence than previously reported) and common features (more common in women) and confirms multifactorial aetiology of facial pain. Significant association with psychological distress and a strong relationship to pain elsewhere in the body suggests that aetiology is not specific to this regional pain.
PMCID: PMC4219861  PMID: 25386229
facial pain; orofacial pain; epidemiology; risk factors
10.  Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique 
Journal of Pain Research  2014;7:313-326.
Chronic musculoskeletal pain conditions are multifaceted, and approximately 20% of the adult population lives with severe chronic pain, with a higher prevalence in women and in lower income groups. Chronic pain is influenced by and interacts with physical, emotional, psychological, and social factors, and a biopsychosocial framework is increasingly applied in clinical practice. However, there is still a lack of assessment procedures based on the activated neurobiological pain mechanisms (ie, the biological part of the biopsychosocial model of pain), which may be a necessary step for further optimizing outcomes after treatments for patients with chronic pain. It has been suggested that chronic pain conditions are mainly driven by alterations in the central nervous system with little or no peripheral stimuli or nociception. In contrast, other authors argue that such central alterations are driven by peripheral alterations and nociceptive input. Microdialysis is an in vivo method for studying local tissue alterations and allows for sampling of substances in the interstitium of the muscle, where nociceptor free nerve endings are found close to the muscle fibers. The extracellular matrix plays a key role in physiologic functions of cells, including the primary afferent nociceptor. The present review mainly concerns the results of microdialysis studies and how they can contribute to the understanding of activated peripheral nociceptive and pain mechanisms in humans with chronic pain. The primary aim was to review molecular studies using microdialysis for the investigation of human chronic muscle pain, ie, chronic masticatory muscle pain, chronic trapezius myalgia, chronic whiplash-associated disorders, and chronic widespread pain/fibromyalgia syndrome. Several studies clearly showed elevated levels of serotonin, glutamate, lactate, and pyruvate in localized chronic myalgias and may be potential biomarkers. These results indicate that peripheral muscle alterations are parts of the activated pain mechanisms in common chronic pain conditions. Muscle alterations have been reported in fibromyalgia syndrome and chronic widespread pain, but more studies are needed before definite conclusions can be drawn. For other substances, results are inconclusive across studies and patient groups.
PMCID: PMC4062547  PMID: 24966693
algesic; biomarker; human; metabolism; nociception; pain
11.  The transition from acute to chronic pain: might intensive care unit patients be at risk? 
Pain remains a significant problem for patients hospitalized in intensive care units (ICUs). As research has shown, for some of these patients pain might even persist after discharge and become chronic. Exposure to intense pain and stress during medical and nursing procedures could be a risk factor that contributes to the transition from acute to chronic pain, which is a major disruption of the pain neurological system. New evidence suggests that physiological alterations contributing to chronic pain states take place both in the peripheral and central nervous systems. The purpose of this paper is to: 1) review cutting-edge theories regarding pain and mechanisms that underlie the transition from acute to chronic pain, such as increases in membrane excitability of peripheral and central nerve fibers, synaptic plasticity, and loss of the function of descending inhibitory pain fibers; 2) provide information on the association between the immune system and pain and its crucial contribution to development of chronic pain syndromes, and 3) discuss mechanisms at brain levels in the nervous system and their contribution to affective (i.e., emotional) states associated with chronic pain conditions. Finally, we will offer suggestions for ICU clinical interventions to attempt to prevent the transition from acute to chronic pain.
PMCID: PMC3488025  PMID: 22898192
Pain; Acute; Chronic; Acute-to-chronic; Intensive care unit; Critical care; Nerve sensitization
12.  Exploring the associations between sleep problems and chronic musculoskeletal pain in adolescents: A prospective cohort study 
Sleep problems and chronic pain are intimately connected, with pain causing poor sleep, which, in turn, leads to increased pain intensity. This may be particularly relevant among adolescents, in whom sleep patterns are more likely to be disrupted. In this study, the relationship between sleep problems at 15 years of age, and chronic regional pain as well as chronic widespread pain at 17 years of age was explored.
The prevalence of musculoskeletal chronic pain in adolescents is estimated to be approximately 4% to 40%. The development of musculoskeletal pain during teenage years could have a marked impact on physical, psychological and social well-being.
To examine whether sleep problems during adolescence are associated with musculoskeletal pain, particularly chronic regional pain and chronic widespread pain.
Using data from the Avon Longitudinal Study of Children, the relationship between sleep problems at 15 years of age and the presence of chronic regional and widespread pain at 17 years of age was explored. Pain data were not available at 15 years of age. A total of 2493 participants with complete data were identified. Relationships among sleep problems and musculoskeletal pain were examined using logistic regression. ORs were calculated after adjusting for sex, ethnicity, socioeconomic position and depression (15 years of age).
Sleep disturbance (usually wakes up more than two or three times), difficulties with hypersomnolence and poor subjective sleep perception were associated with the presence of both musculoskeletal regional and widespread pain. Finally, using ordered logistic regression, poor subjective sleep perception was also found to be associated with greater pain severity in participants with chronic musculoskeletal regional and widespread pain.
The results of the present study suggest an association between sleep problems during adolescence and the presence of musculoskeletal pain at a later stage. These findings are consistent with adult literature suggesting a link between sleep problems and musculoskeletal pain. Given these associations, sleep problems in adolescence may be an important risk factor for musculoskeletal pain.
PMCID: PMC4197758  PMID: 25299477
Adolescence; ALSPAC; Chronic pain; Sleep
13.  Subgroups of musculoskeletal pain patients and their psychobiological patterns – The LOGIN study protocol 
Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated.
The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients.
We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending inhibition (conditioned pain modulation, the diffuse noxious inhibitory control-like effect), as well as measurement of the plasma levels of nerve growth factor and endocannabinoids.
The identification of the underlying pathophysiologic mechanisms in different subgroups of chronic musculoskeletal pain patients will contribute to a mechanism-based subgroup classification. This will foster the development of mechanism-based treatments and holds promise to treat patients more sufficient.
PMCID: PMC3476389  PMID: 22862787
Chronic non-specific musculoskeletal pain; Endocannabinoids; Mental comorbidity; Pain drawing; Pain extent; Quantitative sensory testing; Mechanism-based; Subgroup classification; Nerve growth factor; Trauma
14.  Predictors of Onset of Facial Pain and Temporomandibular Disorders in Early Adolescence 
Pain  2006;129(3):269-278.
There are few prospective studies assessing risk factors for onset of temporomandibular (TMD) pain disorders in any age group. The aim of this prospective cohort study was to identify risk factors for onset of clinically significant TMD pain (i.e., pain meeting research diagnostic criteria for myofascial pain and/or arthralgia) during early adolescence. Subjects were 1,996 boys and girls, initially 11 years old, randomly selected from a large nonprofit health care system. Subjects completed a baseline telephone interview and were followed up with mailed questionnaires every 3 months for 3 years. At baseline and all follow ups, subjects were asked to report the presence of facial pain in the past 3 months. Subjects reporting a first onset of facial pain received a standardized clinical examination. In multivariate analyses, baseline predictors of clinically significant pain included female gender [Odds Ratio (OR) = 2.0, 95% Confidence Interval (CI) = 1.2–3.3] and negative somatic and psychological symptoms including somatization (OR = 1.8, CI = 1.1–2.8), number of other pain complaints (OR = 3.2, CI = 1.7–6.1) and life dissatisfaction (OR = 4.1, CI = 1.9–9.0). Many of the risk factors for onset of clinically significant TMD pain in adolescents are similar to risk factors for onset of TMD and other pain problems in adults, as well as risk factors for onset of other pain conditions in adolescents. These findings suggest that the development of TMD pain in adolescence may reflect an underlying vulnerability to musculoskeletal pain that is not unique to the orofacial region.
PMCID: PMC1979093  PMID: 17134830
temporomandibular disorders; adolescents; gender; chronic pain; somatization; incidence
15.  Pain-related mood influences pain perception differently in fibromyalgia and multiple sclerosis 
Journal of Pain Research  2014;7:81-87.
In patients, the perception of pain intensity may be influenced by the subjective representation of their disease. Although both multiple sclerosis (MS) and fibromyalgia (FM) possibly include chronic pain, they seem to elicit different disease representations because of the difference in their respective etiology, the former presenting evidence of underlying lesions as opposed to the latter. Thus, we investigated whether patients with FM differed from patients with MS with respect to their perception of “own” pain as well as others’ pain. In addition, the psychological concomitant factors associated with chronic pain were considered. Chronic pain patients with FM (n=13) or with MS (n=13) participated in this study. To assess specific pain-related features, they were contrasted with 12 other patients with MS but without chronic pain and 31 controls. A questionnaire describing imaginary painful situations showed that FM patients rated situations applied to themselves as less painful than did the controls. Additionally, pain intensity attributed to facial expressions was estimated as more intense in FM compared with the other groups of participants. There is good evidence that the mood and catastrophizing reactions expressed in FM differentially modulated the perception of pain according to whether it was their own pain or other’s pain.
PMCID: PMC3904836  PMID: 24489475
chronic pain; self and other’s perspective; imaginary pain; facial expression
16.  ZIPping to pain relief: the role (or not) of PKMζ in chronic pain 
Molecular Pain  2013;9:6.
Chronic pain remains a significant clinical problem despite substantial advances in our understanding of how persistent nociceptor stimulation drives plasticity in the CNS. A major theme that has emerged in this area of work is the strong similarity between plasticity involved in learning and memory in CNS regions such as cortex and hippocampus with mechanisms underlying chronic pain development and maintenance in the spinal dorsal horn and other CNS areas such as anterior cingulate cortex (ACC). We, and others have recently implicated an atypical PKC (aPKC), called PKMζ, in the maintenance of pain plasticity based on biochemical assays and the use of a peptide pseudosubstrate inhibitor called ZIP. These studies indicate remarkable parallels between the potential role of PKMζ as a key molecule for the maintenance of long-term memory and long-term potentiation (LTP) and the maintenance of a chronic pain state. On the other hand, very recent studies have disputed the specificity of ZIP and called into question the role of PKMζ as a memory maintenance molecule. Here we critically review the evidence that PKMζ might represent a new target for the reversal of certain chronic pain states. Furthermore, we consider whether ZIP might have other aPKC or even non-aPKC targets and the significance of such off-target effects for evaluating maintenance mechanisms of chronic pain. We conclude that, current controversies aside, utilization of ZIP as a tool to interrogate maintenance mechanisms of chronic pain and further investigations into the potential role of PKMζ, and other aPKCs, in pain plasticity are likely to lead to further insights with the potential to unravel the enigma that is the disease of chronic pain.
PMCID: PMC3621284  PMID: 23433248
17.  The relationship among psychological factors, neglect-like symptoms and postoperative pain after total knee arthroplasty 
Neglect-like symptoms have been defined as a loss of perception of a limb, with pain and excessive effort necessary to move the limb. This phenomenon has been studied in patients with complex regional pain syndrome, but has not been assessed in patients who have undergone orthopedic procedures such as total knee arthroplasty. The authors of this study assessed neglect-like symptoms in a group of 90 patients three and six weeks after total knee arthroplasty.
Persistent postoperative pain has a significant relationship with patient health and satisfaction.
To investigate the prevalence and association of neglect-like symptoms (NLS) and other psychological factors on postoperative pain in patients following total knee arthroplasty (TKA). NLS are defined as the loss of perception of the limb with pain and excessive effort required to move the limb. The authors hypothesized that NLS were an important contributor to postoperative pain.
The factors influencing pain were investigated using a longitudinal study with assessments at three and six weeks postsurgery. The relationships among demographic factors (age, body weight, body mass index), psychological factors (State-Trait Anxiety Inventory and Pain Catastrophizing Scale [PCS]) and NLS with postoperative pain were investigated in 90 patients after TKA. The associations among motor functions (muscle strength of knee extension, range of motion), sensory functions (joint position sense and two-point discrimination in the thigh) and NLS were also investigated.
At three and six weeks after surgery, 36% and 19% of patients, respectively, experienced NLS. In hierarchical multiple regression analysis, NLS and PCS scores were significantly associated with postoperative pain, while joint position sense and range of motion were significantly associated with NLS.
These results suggest that facilitation of sensory integration is important in rehabilitation after TKA because NLS appears to result from impaired sensory integration. The association of PCS scores with postoperative pain and NLS suggests the need to provide appropriate postoperative education to reduce persistent negative thoughts regarding future pain.
PMCID: PMC4197752  PMID: 25101335
Neglect-like symptoms; Pain catastrophizing; Postoperative pain; Postoperative rehabilitation; Total knee arthroplasty
18.  Psychological assessment of factors affecting pain 
Canadian Medical Association Journal  1974;111(11):1213-1215.
Use of traditional stimulus-response models of pain leads to differentiation between organic and psychogenic pain, which is often not helpful, if not dangerous, in treating chronic pain. Pain does not simply reflect bodily damage but also complex psychological malfunctioning. Viewing chronic pain as an obsessional state may often help in treating the entire patient and prevent the physician from being obsessed with the patient's obsession. Psychological assessment of pain should focus on the role of psychological processes in the multifactorial causation of the illness causing the pain, notably their role in illness-proneness in general. Also, iatrogenic psychological distress, associatively precipitated psychological conflict and illness-perpetuating psychological processes should be looked for. A serious obstacle to progress with pain problems is not lack of hard data but conceptual confusion. Before medicine can meaningfully assess psychological factors in pain problems it must first learn to perceive psychological disturbances in medical and surgical patients.
PMCID: PMC1955943  PMID: 4434290
19.  Prevalence of sleep disturbance in patients with low back pain 
European Spine Journal  2010;20(5):737-743.
Low back pain (LBP) is a common health condition that is often associated with disability, psychological distress and work loss. Worldwide, billions of dollars are expended each year trying to manage LBP, often with limited success. Recently, some researchers have reported that LBP patients also report sleep disturbance as a result of their LBP. However, as most of this evidence was obtained from highly selected groups of patients or from studies with small samples, high quality data on prevalence of sleep disturbance for patients with LBP are lacking. It is also unclear whether sleep disturbance is more likely to be reported by patients with recent-onset LBP than by patients with persistent LBP. Finally, it is not known whether high pain intensity, the most relevant condition-specific variable, is associated with higher rates of reported sleep disturbance. The present study aimed to determine the prevalence of reported sleep disturbance in patients with LBP. In addition, we aimed to determine whether sleep disturbance was associated with the duration of back pain symptoms and whether pain intensity was associated with reported sleep disturbance. Data from 1,941 patients obtained from 13 studies conducted by the authors or their colleagues between 2001 and 2009 were used to determine the prevalence of sleep disturbance. Logistic regression analyses explored associations between sleep disturbance, the duration of low back symptoms and pain intensity. The estimated prevalence of sleep disturbance was 58.7% (95% CI 56.4–60.7%). Sleep disturbance was found to be dependent on pain intensity, where each increase by one point on a ten-point visual analogue scale (VAS) was associated with a 10% increase in the likelihood of reporting sleep disturbance. Our findings indicate that sleep disturbance is common in patients with LBP. In addition, we found that the intensity of back pain was only weakly associated with sleep disturbance, suggesting that other factors contribute to sleep problems for LBP patients.
PMCID: PMC3082679  PMID: 21190045
LBP; Sleep; Disturbance; Pain; Prevalence; Chronic pain
20.  Examining nurse empathy for infant procedural pain: Testing a new video measure 
Nurses possess evidence-based knowledge about the importance of pain management in infants and they self-report moderate to high levels of empathy, but the translation to pain care is low. New strategies are required to research this perplexing problem. In this study, a video program was developed and tested for this purpose. Female participants (nurses and allied health controls) were asked to score the infant procedural pain level displayed in the video using a visual analogue scale and a composite score of known infant pain cues. Participants also scored their own sensitivity to painful events. An individual’s motivation to reduce others’ pain is a complex process and the authors surmise that it may be dependent on multiple factors. Additional research is required to probe the issue deeper, and to generate interventions designed to train and motivate nurses to use their knowledge to assess and effectively manage procedural pain experienced by infants.
Research reporting effective pain care strategies exists, yet it is not translated to care. Little is known about how repeated pain exposure has affected nurses’ ability to be empathetic and use their knowledge to provide evidence-based care. Concerns have been raised regarding the validity of self-report empathy instruments; therefore, a novel video program was developed for testing. It was hypothesized that those who viewed infants in painful and nonpainful states would have a measureable empathy (pain rating) response correlating to the level of pain expressed by the infants.
To validate the newly developed Empathy for Infant Pain video program (EIPvp) by determining whether nurse and non-nurse control groups’ pain scores of 24 video clips showing infants undergoing real medical procedures were equal.
A descriptive cross-sectional video judgement study.
Fifty female participants (25 nurses and 25 allied health controls) were asked to score the infant procedural pain level displayed in the EIPvp using a visual analogue scale and a composite score of known infant pain cues. Participants also scored their own sensitivity to painful events.
Participants rated the videos contained in the EIPvp similarly in three categories (no, low or high pain); however, there were consistent differences between groups within the categories. Nurses scored facial cues for all categories higher than the control group. Nurses scored their own pain in hypothetical situations and that of the infants consistently higher than the control group.
The EIPvp yielded predictable responses from both the nurse and non-nurse control groups when scoring the pain expressed in the video clips. Nurses’ detection of pain more often than controls may have been an indication that they have greater knowledge of pain cues, or their empathy levels may have been different as a result of their exposure to, or their perceived relationship with, patients. The EIPvp was validated and has promising potential for training and research purposes.
PMCID: PMC3202373  PMID: 22059191
Empathy; Neonatal pain; Nursing; Pain assessment; Procedure pain; Situational pain
21.  The clinical psychologist and the management of inpatient pain: a small case series 
Recent research has confirmed that between 25% and 33% of all hospitalized patients experience unacceptable levels of pain. Studies further indicate that this reduces patient satisfaction levels, lengthens hospital stays, and increases cost. Hospitals are aiming to discharge patients earlier, and this can interfere with adequate pain management. Therefore, the pain service at Chelsea and Westminster Hospital has adapted to this changing model of care. An increasing body of evidence demonstrates that psychological factors are key components of patients’ pain experiences in both acute and chronic pain. Therefore, it is reasonable to suggest a clinical psychologist should be involved in inpatient pain management. This small study discusses three cases that highlight how patient care could be improved by including a clinical psychologist as part of the inpatient pain team. Two cases particularly highlight the active role of the psychologist in the diagnosis and management of common conditions such as fear and anxiety, along with other psychiatric comorbidities. The management therefore employed an eclectic approach adapted from chronic pain and comprising of behavioral, cognitive behavioral, and dialectical behavioral therapeutic techniques blended with brief counseling. The third case exemplifies the importance of nurse-patient interactions and the quality of nurse-patient relationships on patient outcomes. Here, the psychologist helped to optimize communication and to resolve a difficult and potentially risk-laden situation. This small case series discusses the benefits derived from the involvement of a clinical psychologist in the management of inpatient pain, and therefore illustrates the need for novel initiatives for inpatient pain services. However, future research is warranted to validate this approach.
PMCID: PMC4259554  PMID: 25506221
acute pain; aggression; anxiety; borderline personality disorder; psychology
22.  Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial 
BMC Psychiatry  2007;7:58.
Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available.
Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (Hamilton Depression Rating Scale score ≥ 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship.
This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed.
Trial registration
Current Controlled Trails ISRCTN31263312
PMCID: PMC2174932  PMID: 17963493
23.  Management of non-cardiac chest pain: from research to clinical practice 
Heart  1999;81(4):387-392.
BACKGROUND—Non-cardiac chest pain assessed by cardiologists in their outpatient clinics or by coronary angiography usually has a poor symptomatic functional and psychological outcome. Randomised trials have shown the effectiveness of specialist psychological treatment with those who have persistent symptoms, but such treatment is not always acceptable to patients and may not be feasible in routine clinical settings.
OBJECTIVES—To describe a sample of patients referred to cardiac outpatient clinics from primary care in a single health district who were consecutively reassured by cardiologists that there was not a cardiac cause for their presenting symptom of chest pain. 
DESIGN—Systematic recording of referral and medical information of patients consecutively reassured by cardiologists. Reassessment in research clinic six weeks later (with a view to inclusion in a randomised trial of psychological treatment, which has been separately reported) and followed up at six months. 
SETTING—A cardiac clinic in a teaching hospital providing a district service to patients referred from primary care. 
PATIENTS—133 patients from the Oxfordshire district presenting with chest pain and consecutively reassured that there was no cardiac cause during the recruitment period; 69 had normal coronary angiograms and 64 were reassured without angiography. 
INTERVENTION—A subgroup (n = 56) with persistent disabling chest pain at six weeks were invited to take part in a randomised controlled trial of cognitive behavioural treatment. 
MAIN OUTCOME MEASURES—Standardised interview and self report measures of chest pain, other physical symptoms, mood and anxiety, everyday activities, and beliefs about the cause of symptoms at six week assessment; repeat of self report measures at six months. 
RESULTS—Patients had a good outcome at six weeks, but most had persistent, clinically significant symptoms and distress. Some found the six week assessment and discussion useful. The psychological treatment was helpful to most of those recruited to the treatment trial, but a minority (15%) of those treated appeared to need more intensive and individual collaborative management. Patients reassured following angiography were compared with those reassured without invasive investigation. They had longer histories of chest pain, more often reported breathlessness on exertion, and were more likely to have previously been diagnosed as having angina, treated with antianginal medication, and admitted to hospital as emergencies.
CONCLUSION—These findings suggest a need for "stepped" aftercare, with management tailored according to clinical need. This may range from simple reassurance and explanation in the cardiac clinic to more intensive individual psychological treatment of associated underlying and often enduring psychological problems. Simple ways in which the cardiologist might improve care to patients with non-cardiac chest pain are suggested, and the need for access to specialist psychological treatment discussed.

 Keywords: non-cardiac chest pain; psychological problems; cognitive behavioural treatment
PMCID: PMC1729004  PMID: 10092565
24.  Surgical Treatment for Chronic Pelvic Pain 
The source of chronic pelvic pain may be reproductive organ, urological, musculoskeletal - neurological, gastrointestinal, or myofascial. A psychological component almost always is a factor, whether as an antecedent event or presenting as depression as result of the pain.
Surgical interventions for chronic pelvic pain include: 1) resection or vaporization of vulvar/vestibular tissue for human papillion virus (HPV) induced or chronic vulvodynia/vestibulitis; 2) cervical dilation for cervix stenosis; 3) hysteroscopic resection for intracavitary or submucous myomas or intracavitary polyps; 4) myomectomy or myolysis for symptomatic intramural, subserosal or pedunculated myomas; 5) adhesiolysis for peritubular and periovarian adhesions, and enterolysis for bowel adhesions, adhesiolysis for all thick adhesions in areas of pain as well as thin ahesions affecting critical structures such as ovaries and tubes; 6) salpingectomy or neosalpingostomy for symptomatic hydrosalpinx; 7) ovarian treatment for symptomatic ovarian pain; 8) uterosacral nerve vaporization for dysmenorrhea; 9) presacral neurectomy for disabling central pain primarily of uterine but also of bladder origin; 10) resection of endometriosis from all surfaces including removal from bladder and bowel as well as from the rectovaginal septal space. Complete resection of all disease in a debulking operation is essential; 11) appendectomy for symptoms of chronic appendicitis, and chronic right lower quadrant pain; 12) uterine suspension for symptoms of collision dyspareunia, pelvic congestion, severe dysmenorrhea, cul-desac endometriosis; 13) repair of all hernia defects whether sciatic, inguinal, femoral, Spigelian, ventral or incisional; 14) hysterectomy if relief has not been achieved by organ-preserving surgery such as resection of all endometriosis and presacral neurectomy, or the central pain continues to be disabling. Before such a radical step is taken, MRI of the uterus to confirm presence of adenomyosis may be helpful; 15) trigger point injection therapy for myofascial pain and dysfunction in pelvic and abdominal muscles.
With application of all currently available laparoscopic modalities, 80% of women with chronic pelvic pain will report a decrease of pain to tolerable levels, a significant average reduction which is maintained in 3-year follow-up.
Individual factors contributing to pain cannot be determined, although the frequency of endometriosis dictates that its complete treatment be attempted. The beneficial effect of uterosacral nerve ablation may be as much due to treatment of occult endometriosis in the uterosacral ligaments as to transection of the nerve fibers themselves. The benefit of the presacral neurectomy appears to be definite but strictly limited to midline pain. Appendectomy, herniorraphy, and even hysterectomy are all appropriate therapies for patients with chronic pelvic pain.
Even with all laparoscopic procedures employed, fully 20% of patients experience unsatisfactory results. In addition, these patients are often depressed. Whether the pain contributes to the depression or the depression to the pain is irrelevant to them. Selected referrals to an integrated pain center with psychologic assistance together with judicious prescription of antidepressant drugs will likely benefit both women who respond to surgical intervention and those who do not.
A maximum surgical effort must be expended to resect all endometriosis, restore normal pelvic anatomy, resect nerve fibers, and treat surgically accessible disease. In addition, it is important to provide patients with chronic pelvic pain sufficient psychologic support to overcome the effects of the condition, and to assist them with underlying psychologic disorders.
PMCID: PMC3015288  PMID: 9876726
Laparoscopy; Chronic pelvic pain
25.  Genes Contributing to Pain Sensitivity in the Normal Population: An Exome Sequencing Study 
PLoS Genetics  2012;8(12):e1003095.
Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10−4). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.
Author Summary
Chronic widespread pain is a complex clinical problem. Identification of underlying genetic factors would shed light on the biology of pain and offer targets for novel therapies. We aimed to identify rare genetic variants in the normal population associated with pain sensation by performing exome sequencing on individuals who were more or less sensitive to heat pain. While we did not identify any single variants having large effect, we did observe major group differences between the sensitive and insensitive individuals. Network analysis suggested a role for the angiotensin pathway, which previous work in animal models has suggested is important in pain mediation. Our results cast light on the genetic factors underlying normal pain sensation in humans and the utility of exome analyses. It suggests that further exploration of the angiotensin pathway may reveal novel targets for the treatment of pain.
PMCID: PMC3527205  PMID: 23284290

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