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Processing spatially distributed nociceptive information is critical for survival. The conditioned pain modulation (CPM) response has become a common psychophysical test to examine pain modulation capabilities related to spatial filtering of nociceptive information. Neuroimaging studies have been conducted to elucidate the neural mechanisms underlying the CPM response in health and chronic pain states, yet their findings have not been critically reviewed and synthesized before. This narrative review presents a simplified overview of MRI methodology in relation to CPM assessments and summarizes the findings of neuroimaging studies on the CPM response. The summary includes functional MRI studies assessing CPM responses during scanning as well as functional and structural MRI studies correlating indices with CPM responses assessed outside of the scanner. The findings are discussed in relation to the suggested mechanisms for the CPM response. A better understanding of neural mechanisms underlying spatial processing of nociceptive information could advance both pain research and clinical use of the CPM response as a marker or a treatment target. [ABSTRACT FROM AUTHOR]

Abstract: Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT). Youth between the ages of 11 and 17 years participated. Functional connectivity (FC) was examined through the blood oxygenation level-dependent effect using the left and right amygdala (AMY) as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. Arterial spin labeling was used to assess regional brain activation by examining cerebral blood flow. Increased FC between the left AMY with regions associated with nociceptive processing (eg, thalamus) and right AMY FC changes with areas associated with cognitive functioning (dorsolateral prefrontal cortex) and the default mode network (DMN; parietal lobe) were observed in youth with FAPD after the WL-SPT. These changes were related to changes in pain unpleasantness. Amygdala FC changes post-WL-SPT were also related to changes in pain intensity. Amygdala FC with the DMN in youth with FAPD also differed from healthy controls. Global cerebral blood flow changes were also noted between FAPD and healthy controls, but no significant differences in grey matter were detected either between groups or during the WL-SPT in youth with FAPD. Findings confirm youth with FAPD undergo changes in brain systems that could support the development of biomarkers to enhance understanding of the mechanisms of pain and treatment response. [ABSTRACT FROM AUTHOR]

Abstract: Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness. [ABSTRACT FROM AUTHOR]

Inhibitory pain modulation has been reported to be deficient in adults across different types of chronic pain, including migraine. To determine whether a similar phenomenon occurs in youth, we performed a quantitative sensory testing investigation in adolescents with migraine (N = 19). These patients were compared to healthy adolescents with (Fam-His; N = 20) or without (Healthy; N = 29) a family history of migraine (eg, first-degree relative with migraine). Subjects were first familiarized with the stimuli and visual analogue rating scales using graded noxious stimuli (0°C, 43-49°C range). These data were used to explore potential pain sensitivity differences between the groups. Pain inhibition was assessed by conditioned pain modulation (CPM), which used both suprathreshold heat pain (heat CPM) and pressure pain thresholds (pressure CPM) as the test stimuli before and during cold-water immersion (8°C). In response to the graded heat stimuli, Fam-His participants reported higher pain intensity ratings compared with patients with migraine, who in turn reported higher pain intensity ratings than the healthy controls (F = 3.6, [df = 2, 459], P = 0.027). For heat and pressure CPM, there was no significant group difference in the magnitude of CPM responses. Thus, adolescents with migraine and healthy adolescents have similar inhibitory pain modulation capability, despite having marked differences in pain sensitivity. Although Fam-His participants are asymptomatic, they demonstrate alterations in pain processing, which may serve as markers for prediction of migraine development. [ABSTRACT FROM AUTHOR]

Quantitative sensory testing (QST) is widely used to assess somatosensory function by application of controlled stimuli across a variety of modalities. The aim of the present meta-analysis is to synthesize QST results across a wide array of studies of patients with migraine to identify the QST parameters that are reliably different between patients with migraine and healthy controls. In addition, we aimed to determine whether such differences vary according to stimulus location. A comprehensive literature search (up to January 2017) was conducted, which included studies comparing QST parameters between patients with migraine and healthy controls. For each QST modality, we calculated up to 3 meta-analyses for combined (combined data from multiple testing locations), local (head and neck), and nonlocal (outside the head or neck) locations. A total of 65 studies were included in the meta-analyses. Lower heat and pressure pain thresholds were observed in patients with migraine compared with healthy controls in the combined locations. Importantly, lower pressure pain threshold in patients with migraine was found in local areas but not in nonlocal areas. In addition, patients with migraine had higher pain ratings to cold suprathreshold stimuli for combined and nonlocal areas, and higher pain ratings to electrical suprathreshold stimuli for nonlocal areas. This meta-analysis indicates that the alterations in nociceptive processing of patients with migraine may be modality, measure, and location specific. These results provide researchers and clinicians the evidence to choose QST parameters optimally suited for differentiating patients with migraine and healthy controls. [ABSTRACT FROM AUTHOR]

The role of endogenous analgesic mechanisms has largely been viewed in the context of gain modulation during nociceptive processing. However, these analgesic mechanisms may play critical roles in the extraction and subsequent utilization of information related to spatial and temporal features of nociceptive input. To date, it remains unknown if spatial and temporal filtering of nociceptive information is supported by similar analgesic mechanisms. To address this question, human volunteers were recruited to assess brain activation with functional magnetic resonance imaging during conditioned pain modulation (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial filtering of nociceptive information while OA provides a paradigm for assessing temporal filtering of nociceptive information. CPM and OA both produced statistically significant reductions in pain intensity. However, the magnitude of pain reduction elicited by CPM was not correlated with that elicited by OA across different individuals. Different patterns of brain activation were consistent with the psychophysical findings. CPM elicited widespread reductions in regions engaged in nociceptive processing such as the thalamus, insula, and secondary somatosensory cortex. OA produced reduced activity in the primary somatosensory cortex but was associated with greater activation in the anterior insula, dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal lobule relative to CPM. In the brain stem, CPM consistently produced reductions in activity, while OA produced increases in activity. Conjunction analysis confirmed that CPM-related activity did not overlap with that of OA. Thus, dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information. [ABSTRACT FROM AUTHOR]