The Role of Periaqueductal Gray and Cingulate Cortex During Suppression of Pain in Complex Regional Pain Syndrome

Freund, Wolfgang; Wunderlich, Arthur; Stuber, G.; Mayer, Florian; Steffen, Peter R. P.; Mentzel, M.; Schmitz, Bernd; Weber, Frank

doi:10.1097/ajp.0b013e31821d9063

Cited by 31 publications

(22 citation statements)

References 74 publications

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“…Higher PAG activation in healthy subjects than in patients with complex regional pain syndrome has been observed during tonic painful stimulation and instructions to “distract yourself from the feeling of pain by thinking of a nice holiday or by imagining that the finger is far away from you.” (Freund et al, 2011) Of note, individuals with CRPS were able to suppress the feeling of pain with similar efficiency as healthy individuals during constant maximal pain stimulation.…”

Section: Resultsmentioning

confidence: 96%

“…We identified 54 studies that reported specific PAG activation to pain. The main choice of stimulation was heat pain (25 studies (Becerra et al, 2001; Becerra et al, 1999; Bingel et al, 2007; Bingel et al, 2011; Cahill and Stroman, 2011a; Casey et al, 1994; Derbyshire et al, 2002; Derbyshire et al, 1994; Derbyshire and Osborn, 2009; Eippert et al, 2008b; Eippert et al, 2009; Fairhurst et al, 2007; Helmchen et al, 2008; Kong et al, 2008b; Kong et al, 2009; Kong et al, 2010a; Salomons et al, 2004a; Salomons et al, 2007; Schoell et al, 2010; Strigo et al, 2008; Tracey et al, 2002b; Valet et al, 2004; Villemure and Bushnell, 2009; von Leupoldt et al, 2009a; von Leupoldt et al, 2009b; Yelle et al, 2009a)) followed by electrical (6 studies (Dunckley et al, 2005a; Freund et al, 2011; Gray et al, 2009; Niddam et al, 2007; Piche et al, 2009; Seminowicz and Davis, 2007)), brushing on allodynia regions (5 studies (Iadarola et al, 1998; Lebel et al, 2008; Mainero et al, 2007; Moisset et al, 2011; Petrovic et al, 1999)) rectal distention (4 studies (Mayer et al, 2005; Naliboff et al, 2003; Rosenberger et al, 2009b; Wilder-Smith et al, 2004)), von Frey stimulation (4 studies (Ghazni et al, 2010; Gwilym et al, 2009; Lee et al, 2008; Zambreanu et al, 2005)), various cold pain (Mochizuki et al, 2003; Mohr et al, 2008; Petrovic et al, 2000), chemical pain (Hsieh et al, 1996; Iadarola et al, 1998), laser stimulation (Helmchen et al, 2008; Mobascher et al, 2010), gastric pain (Ladabaum et al, 2001), pressure pain (Giesecke et al, 2006) painful sound (Lamm et al, 2007) and spontaneous pain in fibromyalgia (Napadow et al, 2010) and migraine (Cao et al, 2002). …”

Section: Resultsmentioning

confidence: 99%

“…Of note, this difference persisted even after resolution of the CRPS. In adults with CRPS, the early phase of pain stimulation led to higher PAG activation in controls compared to patients, regardless of stimulating the affected or unaffected region (Freund et al, 2011). …”

Section: Resultsmentioning

confidence: 99%

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Neuroimaging of the periaqueductal gray: State of the field

et al. 2012

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This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

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Neuroimaging of the periaqueductal gray: State of the field

et al. 2012

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“…Using advanced fMRI (7 T), Hahn et al [25] was able to demonstrate additional activation of periaqueductal gray (PAG) which was often not observed using 3T fMRI techniques. PAG is known as a pivot region of the descending pain control system [29]–[31]. These studies suggest that painful peripheral electrical stimulation triggers central responses to aversiveness of painful stimuli and internal descending pain coping mechanisms at the same time, i.e., central sensitization.…”

Section: Discussionmentioning

confidence: 99%

Habituation to Experimentally Induced Electrical Pain during Voluntary-Breathing Controlled Electrical Stimulation (BreEStim)

Beran

et al. 2014

PLoS ONE

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ObjectivePainful peripheral electrical stimulation to acupuncture points was found to cause sensitization if delivered randomly (EStim), but induced habituation if triggered by voluntary breathing (BreEStim). The objective was to systematically compare the effectiveness of BreEStim and EStim and to investigate the possible mechanisms mediating the habituation effect of BreEStim.MethodsEleven pain-free, healthy subjects (6 males, 5 females) participated in the study. Each subject received the BreEStim and EStim treatments in a random order at least three days apart. Both treatments consisted of 120 painful but tolerable stimuli to the ulnar nerve at the elbow on the dominant arm. BreEStim was triggered by voluntary breathing while EStim was delivered randomly. Electrical sensation threshold (EST) and electrical pain threshold (EPT) were measured from the thenar and hypothenar eminences on both hands at pre-intervention and 10-minutes post-intervention.ResultsThere was no difference in the pre-intervention baseline measurement of EST and EPT between BreEStim and EStim. BreEStim increased EPT in all tested sites on both hands, while EStim increased EPT in the dominant hypothenar eminence distal to the stimulating site and had no effect on EPT in other sites. There was no difference in the intensity of electrical stimulation between EStim and BreEStim.ConclusionOur findings support the important role human voluntary breathing plays in the systemic habituation effect of BreEStim to peripheral painful electrical stimulation.

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“…Box 2 | Possible mechanisms involved in complex regional pain syndrome Nerve injury [31][32][33][34] Ischemic reperfusion injury or oxidative stress [35][36][37][38][39][40] Central sensitization [41][42][43] Peripheral sensitization 44 45 Altered sympathetic nervous system function or sympathoafferent coupling [46][47][48][49][50][51][52] Inflammatory and immune related factors Brain changes [78][79][80][81][82][83][84][85][86][87][88][89] Genetic factors [90][91][92] Psychological factors and disuse [93][94][95][96][97][98][99][100][101][102][103] deep tissues after injury have also been suggested as triggers for the onset of CRPS. …”

Section: Incidencementioning

confidence: 99%