Featured Publications

Chen C, Tassou A, Morales V, Scherrer G. Graph theory analysis reveals an assortative pain network vulnerable to attacks. Scientific Reports. 2023 Mar 15;. doi: 10.1101/2023.03.08.531580. PubMed PMID: 36945626; PubMed Central PMCID: PMC10028857.


Ochandarena NE, Niehaus JK, Tassou A, Scherrer G. Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits. Neuropharmacology. 2023 Nov 1;238:109597. doi: 10.1016/j.neuropharm.2023.109597. Epub 2023 Jun 2. PMID: 37271281; PMCID: PMC10494323.


Spinal cord retinoic acid receptor signaling gates mechanical hypersensitivity in neuropathic pain. Cao B, Scherrer G, Chen L. Neuron. 2022 Dec 21;110(24):4108-4124.e6. doi: 10.1016/j.neuron.2022.09.027. Epub 2022 Oct 11. PMID: 36223767


Hyperexcitable arousal circuits drive sleep instability during aging. Li SB, Damonte VM, Chen C, Wang GX, Kebschull JM, Yamaguchi H, Bian WJ, Purmann C, Pattni R, Urban AE, Mourrain P, Kauer JA, Scherrer G, de Lecea L. Science. 2022 Feb 25;375(6583). doi: 10.1126/science.abh3021. PMID: 35201886


Brain circuits for pain and its treatment. Mercer Lindsay N, Chen C, Gilam G, Mackey S, Scherrer G. Science Translational Medicine. 2021 Nov 10;13(619). doi: 10.1126/scitranslmed.abj7360. PMID: 34757810

On the cover

Pain, Pain Go Away. The cover image symbolizes the shattering experience of different types of pain in the human body. In this Special Issue, which is designed to showcase the latest advances in pain research, Review articles discuss the principal brain circuits mediating pain (Lindsay et al.) and insights and challenges associated with the development of analgesic drugs (Jayakar et al.). In addition, three Viewpoint articles highlight promising areas of pain research including inflammatory mechanisms of pain (Kavelaars et al.), sexual dimorphism in pain sensitivity (Navratilova et al.), and development of imaging-based biomarkers for measuring pain (Tracey). Two Research Articles complete the Special Issue, presenting research findings on a new small molecule with analgesic effects in mouse models of pain (Cai et al.) and a cytokine that contributes to inflammatory itch (Tseng and Hoon). These Special Issue articles showcase the encouraging progress made in the field of pain research and the challenges still to be overcome. Credit: Chris Gash.


An amygdalar neural ensemble that encodes the unpleasantness of pain. Corder G*, Ahanonu B*, Grewe BF, Wang D, Schnitzer MJ, Scherrer G. Science. 2019 Jan 18;363(6424):276-281. *Co-first authors. doi: 10.1126/science.aap8586. PMID: 30655440


Kappa opioid receptor distribution and function in primary afferents. Snyder LM, Chiang MC, Loeza-Alcocer E, Omori Y, Hachisuka J, Sheahan TD, Gale JR, Adelman PC, Sypek EI, Fulton SA, Friedman RL, Wright MC, Duque MG, Lee YS, Hu Z, Huang H, Cai X, Meerschaert KA, Nagarajan V, Hirai T, Scherrer G, Kaplan DH, Porreca F, Davis BM, Gold MS, Koerber HR, Ross SE. Neuron. 2018 Sep 19;99(6):1274-1288.e6. doi: 10.1016/j.neuron.2018.08.044. PMID: 30236284


Optical activation of TrkA signaling. Duan L, Hope JM, Guo S, Ong Q, François A, Kaplan L, Scherrer G, Cui B. ACS Synth Biol. 2018 Jul 20;7(7):1685-1693. doi: 10.1021/acssynbio.8b00126. Epub 2018 Jul 12. PMID: 29975841


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Endogenous and exogenous opioids in pain. Corder G*, Castro DC*, Bruchas MR, Scherrer G. Annu Rev Neurosci. 2018 Jul 8;41:453-473. *Co-first authors. doi: 10.1146/annurev-neuro-080317-061522. Epub 2018 May 31. PMID: 29852083 


Functional divergence of delta and mu opioid receptor organization in CNS pain circuits. Wang D, Tawfik VL, Corder G, Low SA, François A, Basbaum AI, Scherrer G. Neuron. 2018 Apr 4;98(1):90-108.e5. doi: 10.1016/j.neuron.2018.03.002. Epub 2018 Mar 22. PMID: 29576387

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On the cover

Cellular interactions between delta and mu opioid receptors (DORs and MORs) are thought to regulate opioid analgesia. However, the neurons in which such interactions could occur within pain neural circuits in vivo remains elusive. In this issue of Neuron, Wang et al. showed that DOR and MOR are present in mostly different populations of nociceptive neurons in the spinal cord and brain, indicating that they may control distinct aspects of pain experience. The cover image illustrates the interactions between two butterflies, DOR and MOR, flying over an opium poppy flower. The butterflies’ wing color patterns show DOR-MOR segregated expression in dorsal horn pain neurons (left) and co-expression in ventral horn neurons constituting motor neural circuits (right). Artwork by Dong Wang.

 

Media articles


A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. François A, Low SA, Sypek EI, Christensen AJ, Sotoudeh C, Beier KT, Ramakrishnan C, Ritola KD, Sharif-Naeini R, Deisseroth K, Delp SL, Malenka RC, Luo L, Hantman AW, Scherrer G. Neuron. 2017 Feb 22;93(4):822-839.e6. doi: 10.1016/j.neuron.2017.01.008. Epub 2017 Feb 2. PMID: 28162807 


Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Corder G*, Tawfik VL*, Wang D*, Sypek EI*, Low SA, Dickinson JR, Sotoudeh C, Clark JD, Barres BA, Bohlen CJ, Scherrer G. Nature Medicine. 2017 Feb;23(2):164-173. *Co-first authors. doi: 10.1038/nm.4262. Epub 2017 Jan 16. PMID: 28092666

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On the cover

Corder, Tawfik, Wang, Sypek et al. establish that mu opioid receptors (MORs) on peripheral nociceptor neurons, but not microglia, are responsible for opioid-related side-effects of tolerance and opioid-induced hyperalgesia. They further demonstrate that a commercially available peripherally-restricted opioid antagonist, methylnaltrexone bromide, mitigates these side effects when co-administered with morphine. Image depicts mouse spinal cord with Oprm1 mRNA (coding for MOR, fuchsia) concentrated in neurons but not microglia (CD11b, yellow). Image credit: Vivianne Tawfik.

 

Media articles

 

In vivo interrogation of spinal mechanosensory circuits. Christensen AJ, Iyer SM, François A, Vyas S, Ramakrishnan C, Vesuna S, Deisseroth K, Scherrer G, Delp SL. Cell Reports. 2016 Nov 1;17(6):1699-1710. doi: 10.1016/j.celrep.2016.10.010. PMID: 27806306 


Structure-based discovery of opioid analgesics with reduced side effects. Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hübner H, Huang XP, Sassano MF, Giguère PM, Löber S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK. Nature. 2016 Sep 8;537(7619):185-190. doi: 10.1038/nature19112. Epub 2016 Aug 17. PMID: 27533032


Input- and cell-type-specific endocannabinoid-dependent LTD in the striatum. Wu YW, Kim JI, Tawfik VL, Lalchandani RR, Scherrer G, Ding JB. Cell Reports. 2015 Jan 6;10(1):75-87. doi: 10.1016/j.celrep.2014.12.005. Epub 2014 Dec 24. PMID: 25543142 


GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia. Gaillard S, Lo Re L, Mantilleri A, Hepp R, Urien L, Malapert P, Alonso S, Deage M, Kambrun C, Landry M, Low SA, Alloui A, Lambolez B, Scherrer G, Le Feuvre Y, Bourinet E, Moqrich A. Neuron. 2014 Oct 1;84(1):123-136. doi: 10.1016/j.neuron.2014.08.056. Epub 2014 Sep 18. PMID: 25242222 


Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn. Bardoni R, Tawfik VL, Wang D, François A, Solorzano C, Shuster SA, Choudhury P, Betelli C, Cassidy C, Smith K, de Nooij JC, Mennicken F, O'Donnell D, Kieffer BL, Woodbury CJ, Basbaum AI, MacDermott AB, Scherrer G. Neuron. 2014 Mar 19;81(6):1312-1327. doi: 10.1016/j.neuron.2014.01.044. Epub 2014 Feb 27. PMID: 24583022 

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On the cover

Morphine and other mu opioid receptor agonists are gold standard analgesics due to their potent inhibitory action on pain processing mechanisms. In this issue, Bardoni et al. provide evidence that the opioid system also exercises broad control over cutaneous mechanosensation, via delta opioid receptors (DORs). The authors show that DOR, depicted in light blue, is expressed by mechanosensory neurons that constitute touch-encoding organs in the skin, including circumferential endings around hair follicles (dark gray). In these neurons, DORs inhibit voltage-gated calcium channels and dampen mechanosensory input to the central nervous system and could represent promising drug targets to combat touch-evoked neuropathic pain.

 

Media articles


Pre- and postsynaptic inhibitory control in the spinal cord dorsal horn. Bardoni R, Takazawa T, Tong CK, Choudhury P, Scherrer G, Macdermott AB. Ann N Y Acad Sci. 2013 Mar;1279:90-6. doi: 10.1111/nyas.12056. Review. PMID: 23531006


VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity. Scherrer G, Low SA, Wang X, Zhang J, Yamanaka H, Urban R, Solorzano C, Harper B, Hnasko TS, Edwards RH, Basbaum AI. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22296-301. doi: 10.1073/pnas.1013413108. Epub 2010 Dec 6. PMID: 21135246 


Cellular and molecular mechanisms of pain. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cell. 2009 Oct 16;139(2):267-84. doi: 10.1016/j.cell.2009.09.028. Review. PMID: 19837031 


Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Scherrer G, Imamachi N, Cao YQ, Contet C, Mennicken F, O'Donnell D, Kieffer BL, Basbaum AI. Cell. 2009 Jun 12;137(6):1148-59. doi: 10.1016/j.cell.2009.04.019. PMID: 19524516 

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On the cover

How different opioid receptor subtypes regulate pain is unclear. It is generally considered that the delta and mu opioid receptors (DOR and MOR, respectively) co-occur in subsets of pain fibers (nociceptors), where they coordinately regulate pain. In this issue of Cell, Scherrer et al. demonstrate that the MOR and DOR are, in fact, expressed by different nociceptor populations. The authors further show that the segregated MOR and DOR distribution is paralleled by a selective functional contribution of the two receptors to the control of heat and mechanical pain, respectively. Photo credit: Opium poppy field in France, by Wolfgang Horlacher. Used under the terms of the GNU Free Documentation License.


Knockin mice expressing fluorescent delta-opioid receptors uncover G protein-coupled receptor dynamics in vivo. Scherrer G, Tryoen-Tóth P, Filliol D, Matifas A, Laustriat D, Cao YQ, Basbaum AI, Dierich A, Vonesh JL, Gavériaux-Ruff C, Kieffer BL. Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9691-6. Epub 2006 Jun 9. PMID: 16766653