Ruth Moont

'Pain inhibits pain' mechanisms: Is pain modulation simply due to distraction?

&NA; ‘Diffuse noxious inhibitory controls’ (DNIC), a form of supraspinal descending endogenous analgesia, requires a noxious conditioning stimulus for pain attenuation. This may be partly dependent on a distraction effect. The term “conditioned pain modulation” (CPM) has recently been introduced to describe the psychophysical paradigm to test DNIC. The present study aimed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation. Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers. For conditioning, the right hand was immersed in 46.5 °C water. Distraction was provided by three different difficulty levels of continuous cognitive visual tasks. Experimental blocks consisted of test pain: (1) alone; ‘baseline’, (2) with conditioning pain; ‘CPM’, (3) with distraction; ‘distraction’ and (4) with conditioning pain and distraction; ‘combined’. They were randomized and repeated three times and pain intensity and unpleasantness rated. Results showed an overall effect of experimental block on test pain intensity (P = 0.0125). Post‐hoc tests revealed a significant reduction in pain intensity ratings under Combined (21.2 ± 2.3; mean ± SEM) compared to CPM alone (16.0 ± 2.3) (P < 0.05). Furthermore, at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM. Based on the additive effect of CPM and distraction on pain inhibition, and the cases of no distraction despite CPM, we suggest that CPM acts independently from distraction.

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

&NA; For most healthy subjects, both subjective pain ratings and pain‐evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal‐bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source‐localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot‐water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250–300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain‐controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. The orbitofrontal cortex and the amygdala seem to play a pivotal early role in pain inhibition under conditioned pain modulation.

Neurophysiology of the Cortical Pain Network: Revisiting the Role of S1 in Subjective Pain Perception Via Standardized Low-Resolution Brain Electromagnetic Tomography (sLORETA)

UNLABELLED Multiple studies have supported the usefulness of standardized low-resolution brain electromagnetic tomography (sLORETA) in localizing generators of scalp-recorded potentials. The current study implemented sLORETA on pain event-related potentials, primarily aiming at validating this technique for pain research by identifying well-known pain-related regions. Subsequently, we pointed at investigating the still-debated and ambiguous topic of pain intensity coding at these regions, focusing on their relative impact on subjective pain perception. sLORETA revealed significant activations of the bilateral primary somatosensory (SI) and anterior cingulate cortices and of the contralateral operculoinsular and dorsolateral prefrontal (DLPFC) cortices (P < .05 for each). Activity of these regions, excluding DLPFC, correlated with subjective numerical pain scores (P < .05 for each). However, a multivariate regression analysis (R = .80; P = .024) distinguished the contralateral SI as the only region whose activation magnitude significantly predicted the subjective perception of noxious stimuli (P = .020), further substantiated by a reduced regression model (R = .75, P = .008). Based on (1) correspondence of the pain-activated regions identified by sLORETA with the acknowledged imaging-based pain-network and (2) the contralateral SI proving to be the most contributing region in pain intensity coding, we found sLORETA to be an appropriate tool for relevant pain research and further substantiated the role of SI in pain perception. PERSPECTIVE Because the literature of pain intensity coding offers inconsistent findings, the current article used a novel tool for revisiting this controversial issue. Results suggest that it is the activation magnitude of SI, which solely establishes the significant correlation with subjective pain ratings, in accordance with the classical clinical thinking, relating SI lesions to diminished perception of pain. Although this study cannot support a causal relation between SI activation magnitude and pain perception, such relation might be insinuated.

Temporal changes in cortical activation during distraction from pain: A comparative LORETA study with conditioned pain modulation

Methods to cognitively distract subjects from pain and experimental paradigms to induce conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls or DNIC) have each highlighted activity changes in closely overlapping cortical areas. This is the first study, to our knowledge, to compare cortical activation changes during these 2 manipulations in the same experimental set-up. Our study sample included thirty healthy young right handed males capable of expressing CPM. We investigated brief consecutive time windows using 32-channel EEG-based sLORETA, to determine dynamic changes in localized cortical potentials evoked by phasic noxious heat stimuli to the left volar forearm. This was performed under visual cognitive distraction tasks and conditioning hot-water pain to the right hand (CPM), both individually and simultaneously. Previously we have shown that for CPM, there is increased activity in frontal cortical regions followed by reduced activation of the somatosensory areas, suggesting a pain inhibitory role for these frontal regions. We now observed that distraction caused a different extent of cortical activation; greater early activation of frontal areas (DLPFC, OFC and caudal ACC at 250-350 ms post-stimulus), yet lesser reduction in the somatosensory cortices, ACC, PCC and SMA after 350 ms post-stimulus, compared to CPM. Both CPM and distraction reduced subjective pain scores to a similar extent. Combining CPM and distraction further reduced pain ratings compared to CPM and distraction alone, supporting the dissimilarity of the mechanisms of pain modulation under these 2 manipulations. The results are discussed in terms of the differential functional roles of the prefrontal cortex.

Preoperative preemptive drug administration for acute postoperative pain: A systematic review and meta-analysis

Preoperative administration of pharmacological substances, such as non‐steroidal anti‐inflammatory drugs or opioids, has been gaining acclaim as a preemptive measure to minimize postoperative pain. This systematic review and meta‐analysis aimed at evaluating the effectiveness of this approach in adults undergoing surgical procedures. MEDLINE, EMBASE and the Cochrane Central Register were searched from inception through January 2015. Data from randomized placebo‐controlled trials were screened, extracted and assessed for risk of bias according to The Cochrane Collaborations Tool by two independent authors. The primary outcome measure was reduction in postoperative analgesic consumption during 24 h post surgery; effects were described as mean differences between the drug and placebo arms with corresponding 95% confidence intervals (CIs) and were pooled using random‐effects models. Potential publication bias was tested using funnel plots and Eggers regression test for funnel plot asymmetry. Screened were 511 records, of which 39 were included in the final synthesis with data from 3172 patients. A significant reduction in postoperative analgesic consumption was observed using preoperative administration of non‐steroidal anti‐inflammatory drugs (NSAIDs; 95% CI, −0.61 to −0.14; 31 comparisons), chiefly by the COX‐2 inhibitors class (95% CI, −0.95 to −0.33; 13 comparisons). Significant reduction was also observed for gabapentin (95% CI, −1.60 to −0.38; 6 comparisons). No significant effects were observed using opioids, propionic acids or oxicam derivatives.

Characteristics of Response to Experimental Pain in Sexually Abused Women

ObjectivesWomen with a history of sexual abuse (SA) commonly report greater pain symptoms. It is still unclear whether enhanced pain susceptibility is the result of altered pain processing and response. Therefore, this pilot study aimed to explore pain sensitivity to experimentally induced pain and associated psychology in women with a history of severe SA. MethodsTwenty-one survivors of severe, long-lasting SA and 21 control women underwent experimentally induced heat pain and completed psychological questionnaires. Pain measures included heat pain thresholds, pain intensity ratings, and pain tolerance in response to contact heat, painful stimulation delivered to the volar forearm. Questionnaires included somatization (Brief Symptom Inventory), personality traits including harm avoidance, novelty seeking, and reward dependence (Cloninger tridimensional personality questionnaire), and levels of dissociation (Dissociative Experiences Scale). ResultsSA women had elevated heat pain thresholds (45.7±2.2°C vs. 43.9±3.1°C; P=0.042) and higher pain intensity ratings (on a 0 to 100 scale: 80.0±26.6 vs. 51.2±27.7; P=0.001). In addition, they had lower tolerability to painful tonic stimulation, greater somatization, and larger harm avoidance scores. Regression analyses showed that higher pain intensity ratings in SA women associated with greater tendency for harm avoidance but not with levels of dissociation. DiscussionWomen with a history of severe SA seem to have a paradoxical pattern of experimental pain response, characterized by both higher pain thresholds and increased pain intensity ratings. This pattern is associated with the personality trait of harm avoidance. Models that might account for these findings are discussed.