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Biomedical subjects

R Norman Harden

Publications and source records attributed to R Norman Harden.

At least 19 recordsLinked to original sources

Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain.

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n = 13 and n = 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n = 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Atrophy↗

Diagnosis of complex regional pain syndrome: signs, symptoms, and new empirically derived diagnostic criteria.

This review will discuss the relevant history of the taxonomy and eventual development of diagnostic criteria of what is currently called complex regional pain syndrome. The authors will take their discussion through the early days (at which time the disorder was called reflex sympathetic dystrophy) through consensus-developing conferences to the current conceptualization of the criteria as published by the International Association for the Study of Pain's Task Force on Taxonomy in 1994. The authors will also mention the recent work of the closed workshop held in Budapest in 2004, where clinical and research criteria were proposed; these criteria were published in 2005. The review will also address issues of staging and subtyping the syndrome, as well as a discussion of the salient signs, symptoms, and tests appropriate for use in the diagnosis.

Complex Regional Pain Syndromes↗

Treatment of complex regional pain syndrome: functional restoration.

In this review, the authors discuss the development of consensus-based treatment guidelines in 1997. They also synthesize the recommendations of a closed workshop held in Budapest in late 2004 that reexamined these treatment guidelines and made further and more detailed recommendations. They explore and develop the rationale for making functional restoration the pivotal treatment algorithm in the management of complex regional pain syndrome, around which all other treatments, such as psychotherapy, drugs, and interventions, revolve. The authors discuss in detail the process of functional restoration and the modalities appropriate to accomplishing that--specifically, the role of the occupational therapist, physical therapist, recreational therapist, and vocational rehabilitation specialist. Medications, interventions, and psychotherapy will be covered in other sections of this series.

Complex Regional Pain Syndromes↗

Biofeedback in the treatment of phantom limb pain: a time-series analysis.

Phantom limb pain (PLP) is a noxious, painful sensation that is perceived to occur in an amputated limb. It has been reported to occur in up to 85% of amputees. This pilot study examined the effectiveness of biofeedback in the treatment of nine individuals with PLP who received up to seven thermal/autogenic biofeedback sessions over the course of 4-6 weeks. Pain was assessed daily using the visual analog scale (VAS), the sum of the sensory descriptors, and the sum of the affective descriptors of the McGill short form. Interrupted time-series analytical models were created for each of the participants, allowing biofeedback sessions to be modeled as discrete interventions. Analyses of the VAS revealed that a 20% pain reduction was seen in five of the nine patients in the weeks after session 4, and that at least a 30% pain reduction (range: 25-66%) was seen in six of the seven patients in the weeks following session 6. Sensory descriptors of pain decreased more than the affective pain descriptors. These preliminary results provide some support for the use of biofeedback in the treatment of PLP and indicate the need for further, definitive study.

Biofeedback, Psychology↗

Medication Quantification Scale Version III: update in medication classes and revised detriment weights by survey of American Pain Society Physicians.

UNLABELLED: The Medication Quantification Scale (MQS) is an instrument with potential clinical and research applications for quantifying medication regimen use in chronic pain populations. The MQS was developed in 1992 and updated in 1998 (MQS II) as a tool to co-quantify 3 relevant aspects of medications prescribed for chronic nonmalignant pain: drug class, dosage, and detriment (risk). This 2003 version (MQS III) is the third iteration of the scale, featuring new detriment weights determined by surveying all physician members of the American Pain Society in the United States via mail. A total of 248 physicians (18%) responded with their opinion as to the detriment of 22 mechanistically distinct medication classes. Overall, the physician ratings of detriment weight were relatively consistent (alpha = .84). The increased number of survey responses encompassed a wide range of disciplines, thus reducing discipline bias and introducing several important changes to MQS scoring. Some medication classes previously rated with low detriment weights (eg, nonsteroidal anti-inflammatory drugs) increased in detriment weight (from 2 to 3.4), whereas other classes previously given high weights (eg, "strong" opioids) received lower detriment ratings (from 5 to 3.4) in this survey. The MQS III must now be validated in clinical and research applications. PERSPECTIVE: The MQS is a tool to objectively quantify pain. It computes a single numeric value for a patient's pain medication profile. This number can be used by both clinicians and researchers to track pain levels through a treatment course or research study.

Analgesics↗

Chronic neuropathic pain. Mechanisms, diagnosis, and treatment.

BACKGROUND: The management of chronic pain represents a significant public health issue in the United States. It is both costly to our health care system and devastating to the patient's quality of life. The need to improve pain outcomes is reflected by the congressional declaration of the present decade as the "Decade of Pain Control and Research," and the acknowledgment in January 2001 of pain as the "fifth vital sign" by the Joint Commission of Healthcare Organizations. REVIEW SUMMARY: At present, therapeutic options are largely limited to drugs approved for other conditions, including anticonvulsants, antidepressants, antiarrhythmics, and opioids. However, treatment based on the underlying disease state (eg, postherpetic neuralgia, diabetic neuropathy) may be less than optimal, in that 2 patients with the same neuropathic pain syndrome may have different symptomatology and thus respond differently to the same treatment. Increases in our understanding of the function of the neurologic system over the last few years have led to new insights into the mechanisms underlying pain symptoms, especially chronic and neuropathic pain. CONCLUSIONS: The rapidly evolving symptom- and mechanism-based approach to the treatment of neuropathic pain holds promise for improving the quality of life of our patients with neuropathic pain.

Chronic Disease↗

Evidence-based clinical practice guidelines for interdisciplinary rehabilitation of chronic nonmalignant pain syndrome patients.

This is an update to evidence-based practice guidelines for chronic nonmalignant pain syndrome patients first published in 1995 and revised in 1999. The current guidelines recommend interdisciplinary-focused rehabilitation, which is goal-directed and time-limited. Emphasis is placed on educating patients in active self-management techniques that stress maximizing function. Integrated treatment involving medical, psychological/behavioral, physical/occupational therapy, and disability/vocational interventions are recommended on an outpatient basis whenever clinically possible. Patient selection criteria are delineated. Updated references providing evidence-based support for the recommendations are provided, including the use of opioids and sedative-hypnotic medications, injection and block procedures, acupuncture, implantable spinal infusion and stimulation devices, and other invasive spinal surgery procedures such as intradiscal electrothermal therapy. Guideline integration and early detection and intervention with chronic pain syndrome patients are encouraged.

Journal Article↗

Phantom limb pain treatment with mirtazapine: a case series.

OBJECTIVES: To pilot the efficacy of mirtazapine for relief of phantom limb pain (PLP); to correlate the putative drug mechanism with theoretical PLP mechanisms; and to develop a rationale for further study of mirtazapine in this population. DESIGN: Open-label case series. SUBJECTS/PATIENTS: Four individuals with PLP for at least 3 months after amputation. METHODS: All subjects received oral mirtazapine between 7.5 and 30 mg/day. An 11-point numeric rating scale (0 to 10) measured pain intensity and relief during monitored outpatient follow-up visits. RESULTS/DISCUSSION: Mirtazapine use improved the PLP experienced by these subjects by at least 50%. Subjects with PLP-related sleeping difficulties reported the greatest pain relief concomitant with improved sleep quality. One subject was able to eliminate the use of a selective serotonin reuptake inhibitor antidepressant while using mirtazapine for PLP and depression without change in mood or affect. Mirtazapine enhances noradrenergic and serotonergic activity and may modulate PLP by central mechanisms. Current concepts of the proposed pathophysiology of PLP and the hypothetical impact of mirtazapine are discussed. CONCLUSION: Mirtazapine may be an effective treatment for PLP that can also potentially enhance sleep and mood. This information provides preliminary reinforcement for more formal, controlled studies concerning mirtazapine use in PLP.

Journal Article↗

Current diagnosis and therapy of complex regional pain syndrome: refining diagnostic criteria and therapeutic options.

Complex regional pain syndrome is a clinically challenging entity both in terms of accurate diagnosis and effective treatment. Complex regional pain syndrome is a post-traumatic painful neurologic syndrome involving the somatosensory, sympathetic and often the somatomotor systems. This complex condition consists of local neurogenic inflammation out of proportion to injury; severe pain in the skin, subcutaneous tissues and joints; and a central hyperexcitability that is often compounded with a sympathetic component. The syndrome is multifaceted manifesting both central and peripheral neurologic pathophysiology, frequently including a prominent psychosocial component. The wide array of possible patient presentations and antecedent pathologies also complicate successful treatment. To further add to the clinical challenges of complex regional pain syndrome, the epidemiology and natural history of complex regional pain syndrome are only partially known; evidence concerning complex regional pain syndrome treatment has grown slowly, due in large part to the vagaries of diagnosis; and research data--when they are available--are difficult to interpret. Thus, in spite of our evolving understanding of this neurologic disorder, in many cases complex regional pain syndrome remains difficult to diagnose and treat successfully.

Causalgia↗

Pharmacotherapy of complex regional pain syndrome.

Complex regional pain syndrome has both nociceptive/inflammatory and neuropathic elements and is always (by definition) associated with abnormal activity of the sympathetic nervous system. There is good evidence that complex regional pain syndrome, as currently conceptualized, ultimately includes central sensitization and has motor abnormalities. The lack of a standard diagnostic test or a specific mechanistically based diagnostic scheme has hindered the conduct of well-designed trials, and to date, there is very little evidence supporting an effective treatment. Fortunately, some randomized, controlled trials of drug therapies have been conducted, and systematic reviews have been published of related neuropathic conditions, from which the results have been extrapolated to clinical use in complex regional pain syndrome. The following article presents an overview of available data regarding drug and interventional treatment options for complex regional pain syndrome and of those relevant pharmacotherapies we can derive from the neuropathy literature. As with most chronic pain syndromes, pharmacotherapy coupled with functional restoration and an interdisciplinary approach to treatment are essential to a successful outcome.

Algorithms↗

Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Aging↗

Chronic pain patients are impaired on an emotional decision-making task.

Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision-making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision-making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects (n = 26), 13.4 in CBP patients (n = 26), and -9.5 in CRPS patients (n = 12), indicating poor performance in the patient groups as compared to the normal controls (P < 0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients (r = -0.75, P < 0.003). Other cognitive abilities, such as attention, short-term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.

Adult↗

Increased systemic catecholamines in complex regional pain syndrome and relationship to psychological factors: a pilot study.

We have demonstrated that subjects with complex regional pain syndrome (CRPS) have asymmetric venous pool plasma concentrations of norepinephrine (NE) when affected and unaffected limbs are compared, with most demonstrating decreased NE levels in the affected limb. This pilot study explored whether systemic venous plasma catecholamine levels in CRPS subjects with sympathetically maintained pain (SMP) differ from those found in healthy volunteers. We also explored whether catecholamine levels were correlated with scores on psychometric measures of depression, anxiety, and personality. Venous blood samples from 33 CRPS/SMP patients (from unaffected limbs) and 30 healthy control subjects were assayed for plasma NE and epinephrine (E) concentrations. Plasma NE levels were significantly higher in the CRPS group (P < 0.001). Statistical comparisons of E levels across groups did not achieve significance (P < 0.06), although 52% of CRPS/SMP patients had E levels exceeding the 95% confidence interval based on control data. Significant positive correlations were found between E levels and scores on the Beck Depression Inventory and Scales 1, 3, and 6 on the Minnesota Multiphasic Personality Inventory-2 (all P < 0.05). This preliminary work suggests that increased NE and E levels in CRPS/SMP patients may result from the pain of CRPS, consequent affective distress, or both. Alternatively, our findings could reflect premorbid adrenergic hyperactivity caused by affective, endocrine, or other pathology, which might predispose these individuals to develop the syndrome. Definitive studies are needed to examine these hypotheses in detail.

Adult↗

Do changes in cognitive factors influence outcome following multidisciplinary treatment for chronic pain? A cross-lagged panel analysis.

Changes in maladaptive cognitions may constitute therapeutic processes of multidisciplinary pain programs. A cross-lagged panel design was used to determine whether (a) early-treatment cognitive change predicted late-treatment outcome index change, but not vice versa; and (b) these effects remained significant with depression change controlled. Ninety chronic pain patients, in a 4-week multidisciplinary program, completed measures of catastrophizing, pain helplessness, depression, pain, interference, and activity level at pre-, mid-, and posttreatment. With depression changes controlled, early-treatment catastrophizing and pain helplessness changes predicted late-treatment outcome index changes, but not vice versa; early-treatment depression changes predicted late-treatment activity changes, but not vice versa. Findings advance understanding of pain treatment process and suggest that negative cognition changes may indeed affect improvements in treatment outcome.

Adaptation, Psychological↗

Predicting total knee replacement pain: a prospective, observational study.

To describe the natural history of pain after total knee arthroplasty and to identify factors predicting excessive postoperative pain, we used a prospective, observational study assessing clinical and radiographic variables preoperatively and at 1, 3, 6, and 12 months after knee replacement. Data sources included the visual analog pain scale and other measures of patient health, psychologic state, and component reliability. Regression analyses were conducted to identify specific factors predictive of postoperative pain, controlling for inequality of variables, and confirmed using regression diagnostics. For 116 patients (149 knees; mean age, 66 years; 55.2% women), significant pain was reported by 72.3%, 44.4%, 22.6%, 18.4%, and 13.1%, respectively. No intergroup differences existed for anesthesia, weight, age, or gender. Patients with greater preoperative pain had more postoperative pain, used more home therapy, and postoperative manipulations. Preoperative depression and anxiety were associated with heightened pain at 1 year. Pain after knee replacement resolves quickly, declining to approximately (1/2) by 3 months. However, one in eight patients report moderate to severe pain 1 year after surgery despite an absence of clinical or radiographic abnormalities. Development of office-based preoperative screening tools and interventions for these patients may reduce postoperative costs and improve patient-perceived outcomes.

Adult↗

Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome?

This study tested for evidence supporting the clinical lore of three sequential stages of complex regional pain syndrome (CRPS) and examined the characteristics of possible CRPS subtypes. A series of 113 patients meeting IASP criteria for CRPS underwent standardized history and physical examinations to assess CRPS signs and symptoms in four domains identified in previous research: pain/sensory abnormalities, vasomotor dysfunction, edema/sudomotor dysfunction, and motor/trophic changes. K-Means cluster analysis was used to derive three relatively homogeneous CRPS patient subgroups based on similarity of sign/symptom patterns in these domains. The resulting CRPS subgroups did not differ significantly regarding pain duration as might be expected in a sequential staging model. However, the derived subgroups were statistically-distinct, and suggested three possible CRPS subtypes: (1) a relatively limited syndrome with vasomotor signs predominating, (2) a relatively limited syndrome with neuropathic pain/sensory abnormalities predominating, and (3) a florid CRPS syndrome similar to "classic RSD" descriptions. Subtype 3 showed the highest levels of motor/trophic signs and possible disuse-related changes (osteopenia) on bone scan, despite having directionally the briefest pain duration of the three groups. EMG/NCV testing suggests that Subtype 2 may reflect CRPS-Type 2 (causalgia). Overall, these results are consistent with limited previous work that argues against three sequential stages of CRPS. However, several distinct CRPS subtypes are suggested, and these could ultimately have utility in targeting treatment more effectively.

Adult↗

An updated interdisciplinary clinical pathway for CRPS: report of an expert panel.

The goal of treatment in patients with complex regional pain syndrome (CRPS) is to improve function, relieve pain, and achieve remission. Current guidelines recommend interdisciplinary management, emphasizing 3 core treatment elements: pain management, rehabilitation, and psychological therapy. Although the best therapeutic regimen or the ideal progression through these modalities has not yet been established, increasing evidence suggests that some cases are refractory to conservative measures and require flexible application of the various treatments as well as earlier consideration of interventions such as spinal cord stimulation (SCS). While existing treatment guidelines have attempted to address the comprehensive management of CRPS, all fail to provide guidance for contingent management in response to a sudden change in the patient's medical status. This paper reviews the current pathophysiology as it is known, reviews the purported treatments, and provides a modified clinical pathway (guideline) that attempts to expand the scope of previous guidelines.

Journal Article↗