Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. This functional magnetic resonance imaging (fMRI) study examined whether placebo analgesia is accompanied by reductions in neural activity in pain-related areas of the brain during the time of stimulation. Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat. Large reductions in pain and in brain activation within pain-related regions (thalamus, somatosensory cortices, insula, and anterior cingulate cortex) occurred during the placebo condition. Results indicate that decreases in activity were related to placebo suggestion and a second factor (habituation/attention/conditioning). Although many factors influence placebo analgesia, it is accompanied by reduction in pain processing within the brain in clinically relevant conditions.

Temporal summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (≥ 0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its temporal summation. We utilized functional magnetic resonance imaging (fMRI) in healthy volunteers to measure brain responses associated with TSSP. Region of interest analysis was used to assess TSSP related brain activation. Eleven pain-free normal subjects underwent fMRI scanning during repetitive heat pulses to the right foot at 0.33 Hz and 0.17 Hz. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP ratings of moderate pain in all subjects. As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), premotor activity (SMA, cerebellum), and pain modulation (rostral ACC).

SUMMARYThe main objective of the present study was to examine daily associations (intraindividual variability or IIV) between sleep and affect in older adults. Greater understanding of these associations is important, because both sleep and affect represent modifiable behaviors that can have a major influence on older adults' health and well-being. We collected sleep diaries, actigraphy, and affect data concurrently for 14 days in 103 community-dwelling older adults. Multilevel modeling was used to assess the sleep-affect relationship at both the group (betweenpersons) and individual (within-person or IIV) levels. We hypothesized that nights characterized by better sleep would be associated with days characterized by higher positive affect and lower negative affect, and that the inverse would be true for poor sleep. Daily associations were found between affect and subjective sleep, only and were in the hypothesized direction. Specifically, nights with greater reported awake time or lower sleep quality ratings were associated with days characterized by less positive affect and more negative affect. Gender was not a significant main effect in the present study, despite previous research suggesting gender differences in the sleepaffect relationship. The fact that self-ratings of sleep emerged as the best predictors of affect may suggest that perceived sleep is a particularly important predictor. Finally, our results suggest exploration of affect as a potential intervention target in late-life insomnia is warranted.

When studying the neural responses to acupuncture with a block-designed paradigm, its temporal dynamics predicted by the general linear model (GLM) conforms to typical "on-off" variations during a limited period of the experiment manipulation. Despite a lack of direct evidence associating its psychophysiological response, numerous clinical reports suggest that acupuncture can provide pain relief beyond a needling session. Therefore, a typical GLM analysis may be insensitive or inappropriate for identifying altered neural responses resulting from acupuncture. We developed a new approach to investigate the dynamics underlying sustained effects of acupuncture. Specifically, we designed two separate models to evaluate the baseline activities (prior to stimulation) and neural activities in sequential epochs, using three block-designed functional runs: acupuncture at acupoint ST36, nonmeridian point (NMP) stimulation, and a visual task. We found that the activity patterns during rest were associated with the stimulus types and that the resting activities might be even higher than that of stimulation phases. Such effects of the elevated activity during rest may reduce or eliminate the activity during stimulus conditions or even reverse the sign of brain activation using conventional GLM analysis. Moreover, such sustained responses, followed by acupuncture at ST36 and NMP, exhibited distinct patterns in wide brain structures, particularly in the limbic system and brainstem. These findings may pose great implications for the design and interpretation of a range of acupuncture neuroimaging studies.

Temporal summation of "second pain" (TSSP) is the result of C-fiber-evoked responses of dorsalhorn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (≥0.33 Hz) and relevant for central sensitization as well as chronic pain. Whereas our previous functional magnetic resonance imaging (fMRI) study characterized neural correlates of TSSP in eleven healthy volunteers, the present study was designed to compare brain responses associated with TSSP across these healthy participants and thirteen fibromyalgia (FM) patients. Volume-of-interest analysis was used to assess TSSP-related brain activation. All participants underwent fMRI-scanning during repetitive heat pulses at 0.33 Hz and 0.17 Hz to the right foot. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP-ratings of moderate pain in all subjects. Experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. When stimulus strength was adjusted to induce equivalent levels of TSSP, no differences in activation of pain-related brain regions occurred across NC and FM groups. Subsequently, the fMRI-data of both groups were combined to increase the power of our statistical comparisons. fMRI-statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including ipsilateral and contralateral thalamus, medial thalamus, S1, bilateral S2, midand posterior insula, rostral and mid-anterior cingulate-cortex. However, the stimulus temperatures necessary to evoke equivalent levels of TSSP and corresponding brain activity were less in FM patients. These results suggest that enhanced neural mechanisms of TSSP in FM are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels.