Publications

BACKGROUND: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. METHODS: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. RESULTS: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. CONCLUSIONS: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

BACKGROUND: Clinical trials of acupuncture in chronic pain have largely failed to demonstrate efficacy of traditional over sham acupuncture. However, it should be noted that sham acupuncture is not inert. OBJECTIVE: To determine if experimental-pressure pain assessment and chemical neuroimaging can identify differential responsiveness to sham as opposed to traditional acupuncture. PATIENTS AND INTERVENTION: Fifty patients with fibromyalgia were randomized to either 9 traditional (TA) or sham (SA) acupuncture treatments over a period of 4 weeks. Both participants and assessors were blinded. MAIN OUTCOME MEASURES: The main outcome measures were pressure-pain sensitivity at the thumbnail, insular glutamate+glutamine (Glx), and clinical pain. RESULTS: PATIENTS WITH LOW PAIN SENSITIVITY (LPS), BUT NOT WITH HIGH PAIN SENSITIVITY (HPS), HAD A SIGNIFICANTLY REDUCED CLINICAL PAIN RESPONSE TO SA (CHANGE IN MEAN [STANDARD DEVIATION (SD)]: HPS -8.65 [7.91]; LPS -2.14 [6.68]; p=0.03). This relationship was not the case for TA (HPS -6.90 [4.51]; LPS -6.41 [9.25]; p=0.88). SA-treated patients who were more sensitive also had greater baseline levels of insular Glx than patients who were less sensitive (Glx mean [SD]: HPS 11.3 [1.18]; LPS 10.2 [0.54]; p=0.04). CONCLUSIONS: Pressure-pain testing may identify patients who are less likely to respond to SA. This effect may relate to the levels of brain excitatory neurotransmitters.

PURPOSE OF REVIEW: Gastrointestinal motility disorders (GMDs) are common in the ICU. When encountering these problems, one typically thinks of prokinetics. This review summarizes current evidence of treatments. RECENT FINDINGS: Prokinetics are not the first-line therapy for GMDs. In fact, the clinical implications of using prokinetic agents are rather controversial. Current evidence on alternative treatment modalities such as fluid and electrolyte management, laxatives, opioid antagonists, purgative enemas, acupuncture, physical therapies and probiotics is growing. SUMMARY: Current state of the art to treat GMDs is primarily focused at the elimination of underlying trigger factors. Fluid and electrolyte management as well as laxatives and peripherally acting μ-opioid receptor antagonists are the recommended first-line therapies that can be complemented with prokinetics. Acupuncture as well as physical modalities, such as massage or warming of the abdomen, is promising with few side-effects and should be considered as well.

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.

BACKGROUND: The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. CONCLUSIONS: Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies.

The sensation of itch - defined as unpleasant sensation inducing the urge to scratch - is processed by a network of different brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational patterns. Patients with atopic eczema show different activation patterns and kinetics compared to healthy volunteers. This review summarizes current studies investigating itch in the brain.

BACKGROUND: Malnutrition remains a severe problem in the recovery of critically ill patients and leads to increased in-hospital morbidity and in-hospital stay. Even though early enteral nutrition has been shown to improve overall patient outcomes in the intensive care unit (ICU), tubefeed administration is often complicated by delayed gastric emptying and gastroesophageal reflux. Acupuncture has been successfully used in the treatment and prevention of perioperative nausea and vomiting. In this study we evaluated whether acupuncture can improve gastric emptying in comparison with standard promotility drugs in critically ill patients receiving enteral feeding. METHODS: Thirty mechanically ventilated neurosurgical ICU patients with delayed gastric emptying, defined as a gastric residual volume (GRV) >500 mL for ≥ 2 days, were prospectively and randomly assigned to either the acupoint stimulation group (ASG; bilateral transcutaneous electrical acupoint stimulation at Neiguan, PC-6) or the conventional promotility drug treatment group (DTG) over a period of 6 days (metoclopramide, cisapride, erythromycin). Patients in the ASG group did not receive any conventional promotility drugs. Successful treatment (feeding tolerance) was defined as GRV <200 mL per 24 hours. RESULTS: Demographic and hemodynamic data were similar in both groups. After 5 days of treatment, 80% of patients in the ASG group successfully developed feeding tolerance versus 60% in the DTG group. On treatment day 1, GRV decreased from 970 ± 87 mL to 346 ± 71 mL with acupoint stimulation (P = 0.003), whereas patients in the DTG group showed a significant increase in GRV from 903 ± 60 mL to 1040 ± 211 mL (P = 0.015). In addition, GRV decreased and feeding balance (defined as enteral feeding volume minus GRV) increased in more patients in the ASG group (14 of 15) than in the DTG group (7 of 15; P = 0.014). On treatment day 1, the mean feeding balance was significantly higher in the ASG group (121 ± 128 mL) than in the DTG group (-727 ± 259 mL) (P = 0.005). Overall, the feeding balance improved significantly on all days of treatment in comparison with the DTG group. Patients in the DTG group did not show an increase in feeding balance until day 6. CONCLUSIONS: We introduce a new protocol for acupuncture administration in the critical care setting. We demonstrated that this protocol was more effective than standard promotility medication in the treatment of delayed gastric emptying in critically ill patients. Acupoint stimulation at Neiguan (PC-6) may be a convenient and inexpensive option (with few side effects) for the prevention and treatment of malnutrition in critically ill patients.