Pain
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Context can influence the experience of any event. For instance, the thought that "it could be worse" can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. ⋯ Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced "hedonic flip" of pain.
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Bone cancer pain has a strong impact on the quality of life of patients, but is difficult to treat. Better understanding of the pathogenic mechanisms underlying bone cancer pain will likely lead to the development of more effective treatments. In the present study, we investigated whether inhibition of KCNQ/M channels contributed to the hyperexcitability of primary sensory neurons and to the pathogenesis of bone cancer pain. ⋯ On the contrary, activation of the KCNQ/M channels with retigabine not only inhibited the hyperexcitability of these small DRG neurons, but also alleviated mechanical allodynia and thermal hyperalgesia in bone cancer rats, and all of these effects of retigabine could be blocked by KCNQ/M-channel antagonist XE-991. These results suggest that repression of KCNQ/M channels leads to the hyperexcitability of primary sensory neurons, which in turn causes bone cancer pain. Thus, suppression of KCNQ/M channels in primary DRG neurons plays a crucial role in the development of bone cancer pain.
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Single nucleotide polymorphisms (SNPs) in the serotonergic (5HT) system seem to have modulatory effects on depression and physical function. Preliminary evidence suggests that gene×environment interactions play a role in the development of depression, with somatic complaints serving as environmental stressors. We hypothesized that pain intensity may serve as a stress factor that modulates the association between SNPs in the 5HT system and depression. ⋯ Furthermore, women homozygous for either the 5HTR1A G allele or the 5HTR2A A allele had lower levels of physical functioning than patients with the other genotypes. These results suggest that 5HTR1A and 5HTR2A promoter variations have gender-dependent modulatory effects on depression and physical function in patients with pain. Furthermore, this study demonstrates that pain after lumbar surgery modulates the association between 5HT gene polymorphisms and depression.