Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli.

BACKGROUND: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. METHODS: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. RESULTS: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. CONCLUSION: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. PERSPECTIVE: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Individual differences in pain sensitivity vary as a function of precuneus reactivity.

Although humans differ widely in how sensitive they are to painful stimuli, the neural correlates underlying such variability remains poorly understood. A better understanding of this is important given that baseline pain sensitivity scores relate closely to the risk of developing refractory, chronic pain. To address this, we used a matched perception paradigm which allowed us to control for individual variations in subjective experience. By measuring subjective pain, nociceptive flexion reflexes, and, somatosensory evoked brain potentials (with source localization analysis), we were able to map the brain's sequential response to pain while also investigating its relationship to pain sensitivity (i.e. change in the stimulation strength necessary to experience pain) and spinal cord activity. We found that pain sensitivity in healthy adults was closely tied to pain-evoked responses in the contralateral precuneus. Importantly, the precuneus did not contribute to the actual representation of pain in the brain, suggesting that pain sensitivity and pain representation depend on separate neuronal sub-systems.

Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty.

BACKGROUND AND PURPOSE: Many psychological factors are known to influence pain perception. Among them, intolerance of uncertainty (IU) may play a key modulating role in situations where uncertainty prevails, especially uncertainty regarding the timing of painful events. The objective of this study was to explore the impact of individual differences in IU on pain perception during predictable and unpredictable stimulation timings. We hypothesized that people with high IU, as opposed to those with low IU, would perceive more pain when the timing of painful stimulations cannot be predicted, as compared to when they can. METHODS: Twenty (20) healthy adults, aged between 18 and 35 years old, were recruited. Painful sensations were provoked using transcutaneous electrical stimulations of the right sural nerve. By measuring IU (Intolerance of Uncertainty Scale) and subjective pain (verbal numerical rating scale), it was possible to test the relationship between IU and pain perception, by simulating predictable and unpredictable painful experiences. This was done through cued shock interval (CSI) blocks, with either variable timing or fixed timings (long or short time frame). Self-administered questionnaires were also used to measure pain hypervigilance, pain catastrophizing, state anxiety, and trait anxiety. RESULTS: Pearson correlations confirmed the presence of an association (r=0.63) between IU and the change in pain intensity provoked by unpredictable stimulation timings. Importantly, this association was significant only for stimulations provided at long CSIs, indicating that higher IU scores predicted higher pain intensity scores when stimulation timings became unpredictable, and when the cued delay was long. No association was found between pain scores and other psychological variables. CONCLUSIONS: Our results show that IU moderately correlates to the change in pain intensity provoked by unpredictable stimulation timings. High IU scores were associated with a worsening of the subjective pain experience, especially during long delays in an unpredictable situation. These observations suggest that IU could be considered as a psychological variable that is able to influence pain perception in certain situations. IMPLICATIONS: Assessing and addressing IU could be an added value in pain-related therapy, especially in chronic pain.

Relationship between blood- and cerebrospinal fluid-bound neurotransmitter concentrations and conditioned pain modulation in pain-free and chronic pain subjects.

UNLABELLED: Descending pain inhibition is an endogenous pain control system thought to depend partially on the activation of bulbospinal monoaminergic pathways. Deficits in descending pain inhibition have been reported in numerous human chronic pain conditions, but there is currently no consensus regarding the neurochemical correlates responsible for this deficit. The aims of this study were to 1) assess the efficacy of descending pain inhibition in pain-free and chronic pain subjects, 2) screen for changes in centrally (ie, cerebrospinal fluid) and peripherally (ie, plasma) acting monoamine concentrations, and 3) explore the relationship between descending pain inhibition and monoamine neurotransmitter concentrations. Our results clearly show a deficit in pain inhibition, along with lower plasma norepinephrine and metanephrine concentrations in chronic pain subjects, compared to pain-free subjects. No differences were found in cerebrospinal fluid neurotransmitter concentrations. Finally, our results revealed a positive relationship between blood-bound norepinephrine and metanephrine concentrations and the efficacy of descending pain inhibition. Thus, basal monoamine levels in blood were related to descending pain inhibition. This finding supports the emerging idea that individual differences in descending pain inhibition may be linked to individual differences in peripheral processes, such as monoamines release in blood, which are possibly related to cardiovascular control. PERSPECTIVES: This article presents psychophysical and neurochemical findings that indicate that the latent potential of descending pain inhibitory responses is associated with differential activity in peripheral processes governed by monoamine neurotransmitter release, bringing insights into the relationship between descending pain inhibition and cardiovascular control in humans.

Sex differences in the neural representation of pain unpleasantness.

UNLABELLED: Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. PERSPECTIVE: This article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain.

Effects of surgical resection on the evolution of quality of life in newly diagnosed patients with glioblastoma: a report on 19 patients surviving to follow-up.

OBJECTIVE: Although aggressive tumor resection favors survival in neuro-oncology, its effects on quality of life (QOL) are largely unspecified. The objective of the present study, therefore, was to study the relationship between tumor resection and QOL. METHODS: We conducted a longitudinal study among 35 patients presenting with a suspected, and later confirmed, glioblastoma multiforme tumor. Following surgery, all patients received radiation therapy with concomitant temozolomide. Tumor volumes were segmented manually, and extent of resection was calculated by comparing pre- and post-operative volumes. QOL was obtained at intake and 3 months later, using the Sherbrooke Neuro-Oncology Assessment Scale. Change in QOL was determined by computing the difference between intake and follow-up data. Confounds were controlled for by detrending change in QOL scores from the effects of age, initial tumor volume, tumor location, and baseline QOL. RESULTS: Results showed that larger tumors at intake provoke increased pain (mostly headaches; r = 0.41, p = 0.015) and decreased social support/acceptance of disease (r = 0.43, p = 0.009). Results also showed that compared to biopsies, craniotomies were associated with preserved well-being across nearly all domains of QOL. When extent of resection was analyzed more specifically, results confirmed that larger resections prevented the decay in functional well-being (r = 0.616, p = 0.005) and neurocognitive function (r = 0.51, p = 0.026) typically observed as time progresses. Larger resections were also independently associated with prolonged survival. CONCLUSIONS: Although the data were obtained from a relatively small sample of patients, results indicate that aggressive resections avert decay in QOL, and thus prolong optimized survival.

A deficit in peripheral serotonin levels in major depressive disorder but not in chronic widespread pain.

OBJECTIVES: It has been proposed that serotonin dysfunctions underlie the pathophysiology of various mood disorders (including major depressive disorder, MDD) and chronic pain conditions characterized by deficient pain inhibition, such as fibromyalgia (FM). There is reliable data showing that serotonin disturbances are involved in the pathophysiology of MDD. However, in the case of FM, results published so far are less consistent. Therefore, the current cross-sectional study sought to measure plasma serotonin levels in FM patients, MDD patients, and healthy controls (HC). METHODS: Twenty-nine FM patients, 17 MDD patients, and 57 HC were recruited who did not differ in terms of age, sex, and the presence or absence of a regular menstrual cycle. Plasma samples were analysed with mass spectrometry. RESULTS: Serotonin levels were decreased in MDD patients, relative to FM patients and HC. Post hoc analyses showed that serotonin levels were decreased in FM patients taking antidepressants, relative to HC, but not in drug-free FM patients. Moreover, serotonin levels were negatively correlated with mood symptoms across groups. DISCUSSION: Our results further confirm that MDD is associated with decreased serotonin levels, but that serotonin levels are not altered in FM per se, and suggest that 5-Hydroxytryptamine is related to mood symptoms in these patient groups. Our results also suggest that the taking of antidepressant is a major confound to consider when studying serotonin functioning in FM. The long-term use of antidepressants in FM may lead to serotonin depletion. Conversely, serotonin depletion may be before the taking of antidepressants in FM.

Quality of life in neurooncology--age matters.

OBJECT: Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients. METHODS: In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (< or = 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor. RESULTS: After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults. CONCLUSIONS: These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs.