scholarly journals The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey

2020 ◽  
Author(s):  
Elena Makovac ◽  
Alessandra Venezia ◽  
David Hohenschurz-Schmidt ◽  
Ottavia Dipasquale ◽  
Jade B Jackson ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Functional Connectivity ◽  
Pain Control ◽  
Brain Regions ◽  
Pain Modulation ◽  
Autonomic Reactivity ◽  
Pain Mechanisms ◽  
Cold Pain ◽  
Periaqueductal Grey ◽  
Descending Pain Modulation

AbstractThere is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored.Here, we sought to determine brain regions mediating ANS and descending pain control associations. 30 participants underwent Conditioned Pain Modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure-only’ and ‘pressure+cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain, were acquired. Heart Rate Variability (HRV) was simultaneously recorded.Low frequency HRV (LF-HRV) and the CPM score were negatively correlated; individuals with higher LF-HRV during pain reported reductions in pain during CPM. PAG-frontal medial cortex (FMC) and PAG-rostral ventro-medial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-FMC functional connectivity mediated the strength of HRV-CPM association. CPM response magnitude was also negatively associated with PAG and positively associated with FMC grey matter volumes.Our multi-modal approach, using behavioral, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments.

The periaqueductal gray and descending pain modulation: why should we study them and what role do they play in chronic pain?

2015 ◽  
Vol 114 (4) ◽  
pp. 2080-2083 ◽  
Author(s):  
Kasey S. Hemington ◽  
Marie-Andrée Coulombe
Keyword(s):  
Chronic Pain ◽  
Back Pain ◽  
Functional Connectivity ◽  
Recent Literature ◽  
Chronic Back Pain ◽  
Periaqueductal Gray ◽  
Pain Modulation ◽  
Pain Research ◽  
Descending Pain Modulation ◽  
Pain Patients

In this Neuro Forum we discuss the significance of a recent study by Yu et al. ( Neuroimage Clin 6: 100–108, 2014). The authors examined functional connectivity of a key node of the descending pain modulation pathway, the periaqueductal gray (PAG), in chronic back pain patients. Altered PAG connectivity to pain-related regions was found; we place results within the context of recent literature and emphasize the importance of understanding the descending component of pain in pain research.

scholarly journals Acupuncture Treatment Compensated the Altered Functional Connectivity in the Pain Modulation System on Primary Dysmenorrhea: A Pilot Study

2020 ◽  
Author(s):  
Cheng-Hao Tu ◽  
Yu-Chen Lee ◽  
Ying-Yu Chen ◽  
Chun-Ming Chen ◽  
Wen-Chi Lu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Acupuncture Treatment ◽  
Brain Regions ◽  
Sham Acupuncture ◽  
Pain Modulation ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Menstrual Pain ◽  
Acupuncture Intervention ◽  
Descending Pain Modulation

Abstract BackgroundPrimary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. We previously reported altered functional connectivity between periaqueductal gray matter and other pain-related brain regions in women with PDM, indicating a maladaptation in the descending pain modulation system. Clinically, acupuncture has been suggested as an effective treatment of PDM. Previous animal studies revealed that acupuncture on specific acupoint can produced analgesic effect via descending pain modulation system. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation after acupuncture treatment in women with PDM. MethodsThirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral acupoint Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention session to measure the spontaneous activity in brain. The functional connectivity maps between periaqueductal gray matter and other pain-related brain regions were generated to reveal the status of descending pain modulation systems.ResultsAfter 8 weeks, both groups reported decreased menstrual pain. However, the patterns of functional connectivity changes in descending pain modulation system were different after the verum or sham intervention. The effect of the verum acupuncture intervention may be underpinned by compensatory and/or resilience changes in descending pain modulation systems, whereas that of the sham acupuncture intervention may be underpinned by cognitive reappraisal of painConclusionsThe dissimilar pattern of the FC alterations after the verum and sham acupuncture indicating that different brain mechanisms may be responsible for the menstrual pain relief in verum or sham acupuncture intervention. These results may contribute to the discussion of whether acupuncture treatment induces therapeutic physiological alterations or its benefit is attributable to the placebo effect.

scholarly journals Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jin Cao ◽  
Yue Zhang ◽  
Hui Li ◽  
Zhaoxian Yan ◽  
Xian Liu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Resting State ◽  
Vagus Nerve Stimulation ◽  
Cingulate Cortex ◽  
Periaqueductal Gray ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Descending Pain Modulation

Abstract Background A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine. Methods Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest. Results Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS. Conclusions Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.

scholarly journals The association between pain‐induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey

2021 ◽  
Author(s):  
Elena Makovac ◽  
Alessandra Venezia ◽  
David Hohenschurz‐Schmidt ◽  
Ottavia Dipasquale ◽  
Jade B Jackson ◽  
...  
Keyword(s):  
Pain Control ◽  
Autonomic Reactivity ◽  
Periaqueductal Grey

REPRINTED WITH PERMISSION OF IASP – PAIN 160 (2019) 2679–2690: Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity

Ból ◽  
2020 ◽  
Vol 21 (3) ◽  
pp. 1-15
Author(s):  
Carina Fernandes ◽  
Marina Pidal-Miranda ◽  
Noelia Samartin-Veiga ◽  
María T. Carrillo-de-la-Peña
Keyword(s):  
Systematic Review ◽  
Chronic Pain ◽  
Concurrent Validity ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Experimental Pain ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Mechanisms ◽  
Chronic Pain Conditions

Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research.

scholarly journals An Investigation of Descending Pain Modulation in Women With Provoked Vestibulodynia (PVD): Alterations of Spinal Cord and Brainstem Connectivity

2021 ◽  
Vol 2 ◽  
Author(s):  
Lindsey R. Yessick ◽  
Caroline F. Pukall ◽  
Gabriela Ioachim ◽  
Susan M. Chamberlain ◽  
Patrick W. Stroman
Keyword(s):  
Spinal Cord ◽  
Functional Connectivity ◽  
Structural Equation ◽  
Brain Regions ◽  
Pain Modulation ◽  
Equation Modeling ◽  
Control Group ◽  
Pain Processing ◽  
Provoked Vestibulodynia ◽  
Fmri Session

The most common subtype of vulvodynia (idiopathic chronic vulvar pain) is provoked vestibulodynia (PVD). Previous imaging studies have shown that women with vulvodynia exhibit increased neural activity in pain-related brain regions (e.g., the secondary somatosensory cortex, insula, dorsal midcingulate, posterior cingulate, and thalamus). However, despite the recognized role of the spinal cord/brainstem in pain modulation, no previous neuroimaging studies of vulvodynia have examined the spinal cord/brainstem. Sixteen women with PVD and sixteen matched Control women underwent a spinal cord/brainstem functional magnetic resonance imaging (fMRI) session consisting of five runs with no painful thermal stimuli (No Pain), interleaved randomly with five runs with calibrated, moderately painful heat stimulation (Pain). Functional connectivity was also assessed in periods before, during, and after, pain stimulation to investigate dynamic variations in pain processing throughout the stimulation paradigm. Functional connectivity in the brainstem and spinal cord for each group was examined using structural equation modeling (SEM) for both Pain and No Pain conditions. Significant connectivity differences during stimulation were identified between PVD and Control groups within pain modulatory regions. Comparisons of Pain and No Pain conditions identified a larger number of connections in the Control group than in the PVD group, both before and during stimulation. The results suggest that women with PVD exhibit altered pain processing and indicate an insufficient response of the pain modulation system. This study is the first to examine the spinal cord/brainstem functional connectivity in women with PVD, and it demonstrates altered connectivity related to pain modulation in the spinal cord/brainstem.

Review of neuroimaging studies related to pain modulation

2011 ◽  
Vol 2 (3) ◽  
pp. 108-120 ◽  
Author(s):  
Lone Knudsen ◽  
Gitte Laue Petersen ◽  
Kathrine Næsted Nørskov ◽  
Lene Vase ◽  
Nanna Finnerup ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Pain Control ◽  
Pain Modulation ◽  
Noxious Stimulus ◽  
Control Mechanisms ◽  
Brain Areas ◽  
Pain Mechanisms ◽  
Essential Information ◽  
Neuroimaging Techniques

AbstractBackground and purpose: A noxious stimulus does not necessarily cause pain. Nociceptive signals arising from a noxious stimulus are subject to modulation via endogenous inhibitory and facilitatory mechanisms as they travel from the periphery to the dorsal horn or brainstem and on to higher brain sites. Research on the neural structures underlying endogenous pain modulation has largely been restricted to animal research due to the invasiveness of such studies (e.g., spinal cord transection, brain lesioning, brain site stimulation). Neuroimaging techniques (e.g., magnetoencephalography (MEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)) provide non-invasive means to study neural structures in humans. The aim is to provide a narrative review of neuroimaging studies related to human pain control mechanisms.Methods: The approach taken is to summarise specific pain modulation mechanisms within the somatosensory (diffuse noxious inhibitory controls, acupuncture, movement), affective (depression, anxiety, catastrophizing, stress) and cognitive (anticipation/placebo, attention/distraction, hypnosis)domains with emphasis on the contribution of neuroimaging studies.Results and conclusions: Findings from imaging studies are complex reflecting activation or deactivation in numerous brain areas. Despite this, neuroimaging techniques have clarified supraspinal sites involved in a number of pain control mechanisms. The periaqueductal grey (PAG) is one area that has consistently been shown to be activated across the majority of pain mechanisms. Activity in the rostral ventromedial medulla known to relay descending modulation from the PAG, has also been observed both during acupuncture analgesia and anxiety-induced hyperalgesia. Other brain areas that appear to be involved in a number of mechanisms are the anterior cingulate cortex, prefrontal cortex, orbitofrontal cortex and nucleus accumbens, but their exact role is less clear.Implications: Neuroimaging studies have provided essential information about the pain modulatory pathways under normal conditions, but much is still to be determined. Understanding the mechanisms of pain control is important for understanding the mechanisms that contribute to failed pain control in chronic pain. Applying fMRI outside the brain, such as in the trigeminal nucleus caudalis of the spinotrigeminal pathway and in the dorsal horn of the spinal cord, and coupling brain activity with activity at these sites may help improve our understanding of the function of brain sites and shed light on functional connectivity in the pain pathway.© 2011 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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