Central opioidergic neurotransmission in complex regional pain syndrome

Klega, André; Eberle, T.; Buchholz, Hans‐Georg; Maus, Sebastian; Maihöfner, Christian; Schreckenberger, Mathias; Birklein, Frank

doi:10.1212/wnl.0b013e3181e7ca2e

Cited by 64 publications

(38 citation statements)

References 36 publications

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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%

Complex regional pain syndrome

Bruehl

2015

BMJ

300

246

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Section: Incidencementioning

confidence: 99%

Complex regional pain syndrome

Bruehl

2015

BMJ

300

246

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“…Adults with CRPS exhibit dynamic changes in brain function (Apkarian et al 2001; Maihöfner et al 2004, 2005, 2006, 2007; Pleger et al 2006; Gieteling et al 2008; Becerra et al 2009; Freund et al 2010; Bolwerk et al 2013), brain chemistry (Fukumoto et al 1999; Grachev et al 2000, 2002; Klega et al 2010), and brain structure (Geha et al 2008; Baliki et al 2011; Barad et al 2014). In children with CRPS, we have previously demonstrated alterations in brain function (Lebel et al 2008; Erpelding et al 2014; Simons et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Rapid treatment-induced brain changes in pediatric CRPS

et al. 2014

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To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex-and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray (PAG), two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

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“…Additionally, trophic alterations in skin, hair, nails, and motor function may also occur. Experimental studies have repeatedly documented that patients with CRPS exhibit profound alterations in brain function (Fukumoto et al 1999;Apkarian et al 2001;Maihöfner et al 2004Maihöfner et al , 2005Maihöfner et al , 2006Pleger et al 2006;Lebel et al 2008;Becerra et al 2009;Freund et al 2010), structure (Geha et al 2008;Baliki et al 2011), andchemistry (Fukumoto et al 1999;Grachev et al 2000Grachev et al , 2002Klega et al 2010). Interestingly, there is growing evidence that chronic pain is also characterized by alterations in resting-state functional connectivity (rsFC) as, for example, patients with chronic pain conditions exhibit altered default mode network and attention network rsFC (Baliki et al 2008;Cauda et al 2009bCauda et al , 2010, as well as greater rsFC between pain-related brain regions compared with healthy controls (Cauda et al 2009a).…”

mentioning

confidence: 99%

Habenula functional resting-state connectivity in pediatric CRPS

Erpelding

Sava

Simons

et al. 2014

Journal of Neurophysiology

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The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10–17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

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Central opioidergic neurotransmission in complex regional pain syndrome

Abstract: These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of regional opioid receptor availability to measures of pain, anxiety, and depression underlines the clinical importance of these findings.

Cited by 64 publications

References 36 publications

Complex regional pain syndrome

Complex regional pain syndrome

Rapid treatment-induced brain changes in pediatric CRPS

Habenula functional resting-state connectivity in pediatric CRPS

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