Transcriptional repressor DREAM regulates trigeminal noxious perception

• Published in: Journal of neurochemistry Vol. 141; no. 4; pp. 544 - 552
• Main Authors: Benedet, Tomaso, Gonzalez, Paz, Oliveros, Juan C., Dopazo, Jose M., Ghimire, Kedar, Palczewska, Malgorzata, Mellstrom, Britt, Naranjo, Jose R.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2017
• Subjects: Animals; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - biosynthesis; calcium; Cathepsin L; Cathepsin L - metabolism; cathepsins; Chronic pain; Dorsal root ganglia; DREAM protein; Enkephalins - biosynthesis; Facial Pain - physiopathology; Ganglia; Gene expression; Genomes; Hyperalgesia - physiopathology; Kv Channel-Interacting Proteins - genetics; Kv Channel-Interacting Proteins - physiology; Lipase; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Monoacylglycerol Lipases - metabolism; monoglyceride lipases; Neurochemistry; Neurons; Nociception - physiology; Nuclei; orofacial pain; Pain; Pain perception; Physical Stimulation; Prodynorphin; Protein Precursors - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - physiology; Rodents; Sensory neurons; Sensory stimulation; Spinal cord; Stimulation; Transcription; Transcriptome; Transgenic animals; Transgenic mice; Trigeminal ganglion; Trigeminal Nerve - physiology; orofacial pain; calcium; monoglyceride lipases; cathepsins; transcriptome
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13584

Expression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons, high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing a dominant active mutant of DREAM in trigeminal neurons show increased responses following orofacial sensory stimulation, which correlates with a decreased expression of prodynorphin and brain‐derived neurotrophic factor in trigeminal ganglia. Genome‐wide analysis of trigeminal neurons in daDREAM transgenic mice identified cathepsin L and the monoglyceride lipase as two new DREAM transcriptional targets related to pain. Our results suggest a role for DREAM in the regulation of trigeminal nociception. This article is part of the special article series “Pain”. Molecular mechanisms regulating trigeminal pain are poorly understood. This lack of basic knowledge is unfortunately reflected in the substantial lack of effective treatment for trigeminal pain. We found that transcriptional repressor DREAM regulates the expression of several pain‐related genes in trigeminal neurons and control trigeminal pain perception. Inhibition of DREAM activity might represent a new therapeutical venue. MGLL, monoglyceride lipase; CTSL, cathepsin L, pDyn, prodynorphin; daDREAM, dominant active DREAM. This article is part of the special article series “Pain”.