R. Norman Harden

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.

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.

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.

Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome

&NA; Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the “Budapest Criteria”) regarding diagnostic accuracy. Structured evaluations of CRPS‐related signs and symptoms were conducted in 113 CRPS‐I and 47 non‐CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.

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

&NA; 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.

The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions

Chronic complex regional pain syndrome (CRPS) is a debilitating pain condition accompanied by autonomic abnormalities. We investigated gray matter morphometry and white matter anisotropy in CRPS patients and matched controls. Patients exhibited a disrupted relationship between white matter anisotropy and whole-brain gray matter volume; gray matter atrophy in a single cluster encompassing right insula, right ventromedial prefrontal cortex (VMPFC), and right nucleus accumbens; and a decrease in fractional anisotropy in the left cingulum-callosal bundle. Reorganization of white matter connectivity in these regions was characterized by branching pattern alterations, as well as increased (VMPFC to insula) and decreased (VMPFC to basal ganglion) connectivity. While regional atrophy differentially related to pain intensity and duration, the strength of connectivity between specific atrophied regions related to anxiety. These abnormalities encompass emotional, autonomic, and pain perception regions, implying that they likely play a critical role in the global clinical picture of CRPS.

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

&NA; 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.

An Updated Interdisciplinary Clinical Pathway for CRPS: Report of an Expert Panel

Abstract: 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 patients 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.

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.

Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study

&NA; We hypothesized that preoperative emotional distress and pain intensity would predict the occurrence of signs and symptoms of complex regional pain syndrome (CRPS) following total knee arthroplasty (TKA). Depression (Beck Depression Inventory, BDI), anxiety (State Trait Anxiety Inventory, STAI), pain (McGill Pain Questionnaire–Short Form, MPQ), and signs/symptoms meeting IASP criteria for CRPS were assessed preoperatively, and at 1‐, 3‐, and 6‐months postoperatively in 77 patients undergoing TKA. The prevalence of subjects fulfilling CRPS criteria was 21.0% at 1 month, 13.0% at 3 months, and 12.7% at 6 months postoperative. Higher preoperative scores on the STAI predicted positive CRPS status at 1‐month follow‐up (P<0.05), with a similar non‐significant trend for preoperative BDI scores (P<0.10). Diagnostic sensitivity for the STAI was good (0.73), with moderate specificity (0.56). Neither measure predicted CRPS at later follow‐up (P>0.10). Greater preoperative pain intensity predicted positive CRPS status at 3‐month (MPQ‐Sensory and MPQ‐Affective; P<0.01) and 6‐month (MPQ‐Sensory) follow‐up (P<0.01), but not at 1‐month (P>0.10). Diagnostic sensitivity was high (0.83–1.00), with moderate specificity (0.53–0.60). Post‐TKA patients with CRPS were more depressed at 1‐month follow‐up (P<0.05) and more anxious at 6‐month follow‐up (P<0.05) than patients with ongoing non‐CRPS pain (all other comparisons non‐significant, P>0.10). Overall, results indicate that CRPS‐like phenomena occur in a significant number of patients early post‐TKA; however, it is not associated with significantly greater complaints of postoperative pain. There appears to be a modest utility for preoperative distress and pain in predicting CRPS signs and symptoms following TKA, although false positive rates are relatively high.