A New Epigenetic Mechanism for Inflammation-Induced Pain
Krishna Ghosh, Yuying Huang, Daozhong Jin, Shao-Rui Chen, and Hui-Lin Pan
(see article e1790242024)
Researchers seek a better understanding of why pain persists following inflammation. In this issue, Ghosh and colleagues detected an important epigenetic contributor to the physiological inflammatory response that may underlie persistent pain. Informed by work suggesting that inflammatory pain is associated with increased expression of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels in sensory neurons, the authors investigated whether there are epigenetic mechanisms supporting this channel upregulation. Using mice, they found that a histone methyltransferase (G9a) may play a role. Inhibition or knockdown of G9a in the spinal cord diminished pain hypersensitivity following inflammation. Furthermore, mice lacking G9a in their sensory neurons did not even develop persistent pain hypersensitivity. These mice with ablated G9a had increased baseline TRPA1 and TRPV1 levels but reduced inflammation-induced upregulation. Thus, G9a may suppress TRPA1 and TRPV1 transcription in normal conditions and promote their transcription during inflammation to promote persistent pain. This study suggests that genetic transcription by G9a is a worthwhile target for treatment.
Reinforcement learning model parameter strength correlated with functional connectivity changes projected onto a brain map. Strength and direction of connectivity changes are depicted as line width and color (orange, positive; blue, negative), respectively. See Fujimoto, Elorette, et al. for more information.
Exploring Dopaminergic Control of Learning and Motivation
Atsushi Fujimoto, Catherine Elorette, Satoka Hashimoto Fujimoto, Lazar Fleysher, Peter H. Rudebeck, and Brian E. Russ
(see article e1301242024)
Dopamine signaling plays a role in cognition, but researchers do not know how selectively manipulating dopamine receptor subtypes impacts cognition. Fujimoto, Elorette, and colleagues explored this in their study by assessing the acute behavioral and brain-wide effects of using dopamine D1 and D2 receptor pharmacological antagonists. The authors systemically administered D1 blocker SCH-23390 and D2 blocker haloperidol while imaging nonhuman primate brains under anesthesia or while they performed a probabilistic learning task. SCH-23390 diminished resting-state functional connectivity across brain-wide networks, especially in corticostriatal areas, and diminished behavioral task performance. Haloperidol administration had the opposite effects. The authors also uncovered distinct cortical and subcortical networks associated with cognitive and motivational dopamine manipulations. In other words, distinct brain-wide networks may contribute to dopaminergic control of learning and motivation, which may prove an important distinction for dopamine system researchers to consider moving forward.
Footnotes
This Week in The Journal was written by Paige McKeon
