Pain
-
Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. ⋯ A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P=1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P=0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P=1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.
-
The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. ⋯ In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory.