​A new fascinating study from the Harvard Medical School (Boston, U.S.A.) adds to the evidence that conservative interventions can retrain the brain (ref. 1). Laura Simons and her colleagues reported marked differences in functional brain connectivity between pediatric complex regional pain syndrome patients and age-sex matched control subjects, but also normalization of such differences following in-house rehabilitation.

The baseline differences in functional brain connectivity between patients and controls include enhanced connectivity between the left amygdala and the prefrontal cortex, parietal lobe, basal ganglia, cingulate cortex, somatosensory cortex, thalamus and cerebellum. Such enhanced brain connectivity networks may explain many complex regional pain syndrome symptoms, including chronic pain, anxiety and motor changes. 

Next, patients underwent intensive in-house rehabilitation comprising of physical therapy, occupational therapy and cognitive behavioral therapy. The aims of the treatment was to improve self-management, decrease negative thing and fears about pain, increasing activity levels in despite of pain and reducing parental attention and protective responses to pain (i.e. family therapy and parent education). The treatment did not include a specific exposure-based treatment like graded exposure in vivo. 

Following the treatment, the patients showed a dampened functional connectivity between the left amygdala and the prefrontal cortex, motor cortex, parietal lobe and bilateral cingulate cortex. The authors speculate that these changes may reflect improved motor function in response to treatment, and note that they correspond with the intensive dose of physical and occupational therapy included in the treatment program. Finally, they found that weakened connectivity was associated with greater decrease in pain-related fear after treatment. 

These findings are compelling, and increase the evidence that conservative interventions are able to retrain the brain in patients with chronic pain. Of particular interest here is the central role of the amygdala, a key brain area involved in the pain (neuro)matrix (ref. 2). The amygdala are often referred to as the fear-memory centre of the brain, as they have a key role in negative emotions, anxiety and pain-related memories. In addition to the amygdala, the anterior cingulate cortex takes part of the central fear network in the brain3. Recent research supports the cardinal role of the amygdala as a facilitator of chronic pain development, including sensitization of central nervous system pain pathways (ref.2-7). In line with this is the finding that the amygdala, as well as the somatosensory cortex and insula, shows less activity during pain delivery in case of positive treatment expectations (ref. 8). Hence, decreasing the activity of the amygdala and its connectivity with other parts of the pain neuromatrix may be crucial for effective chronic pain treatment. 

Further reading about Laura Simons’ work on pediatric chronic pain:
http://www.ncbi.nlm.nih.gov/pubmed/?term=Simons%20LE%5BAuthor%5D 
Or watch her profile on Research Gate: 
https://www.researchgate.net/profile/Laura-Simons

References:  
1. Simons LE, Pielech M, Erpelding N, et al. The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome. Pain 2014; 155(9): 1727-42. 
2. Li Z, Wang J, Chen L, Zhang M, Wan Y. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats. PloS one 2013; 8(8). 
3. Kattoor J, Gizewski ER, Kotsis V, et al. Fear conditioning in an abdominal pain model: neural responses during associative learning and extinction in healthy subjects. PloS one 2013; 8(2): 26. 
4. Hadjikhani N, Ward N, Boshyan J, et al. The missing link: Enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia : an international journal of headache 2013; 29: 29. 
5. Kim JY, Kim SH, Seo J, et al. Increased power spectral density in resting-state pain-related brain networks in fibromyalgia. Pain 2013; 154(9): 1792-7. 
6. Schwedt TJ, Schlaggar BL, Mar S, et al. Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache 2013; 53(5): 737-51. 
7. Simons LE, Moulton EA, Linnman C, Carpino E, Becerra L, Borsook D. The human amygdala and pain: Evidence from neuroimaging. Human brain mapping 2012; 25(10): 22199. 
8. Schmid J, Theysohn N, Gass F, et al. Neural mechanisms mediating positive and negative treatment expectations in visceral pain: A functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers. Pain 2013; 16(13): 00381-3.

Jo Nijs 

2014 Pain in motion