Cells and circuits for amygdala neuroplasticity in the transition to chronic pain
Takaki Kiritoshi,
Vadim Yakhnitsa,
Sudhuman Singh,
Torri D. Wilson,
Sarah Chaudhry,
Benjamin Neugebauer,
Jeitzel M. Torres-Rodriguez,
Jenny L. Lin,
Yarimar Carrasquillo,
Volker Neugebauer
Affiliations
Takaki Kiritoshi
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA
Vadim Yakhnitsa
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA
Sudhuman Singh
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Torri D. Wilson
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Sarah Chaudhry
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Benjamin Neugebauer
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Jeitzel M. Torres-Rodriguez
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Jenny L. Lin
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA
Yarimar Carrasquillo
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Volker Neugebauer
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA; Garrison Institute on Aging, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA; Corresponding author
Summary: Maladaptive plasticity is linked to the chronification of diseases such as pain, but the transition from acute to chronic pain is not well understood mechanistically. Neuroplasticity in the central nucleus of the amygdala (CeA) has emerged as a mechanism for sensory and emotional-affective aspects of injury-induced pain, although evidence comes from studies conducted almost exclusively in acute pain conditions and agnostic to cell type specificity. Here, we report time-dependent changes in genetically distinct and projection-specific CeA neurons in neuropathic pain. Hyperexcitability of CRF projection neurons and synaptic plasticity of parabrachial (PB) input at the acute stage shifted to hyperexcitability without synaptic plasticity in non-CRF neurons at the chronic phase. Accordingly, chemogenetic inhibition of the PB→CeA pathway mitigated pain-related behaviors in acute, but not chronic, neuropathic pain. Cell-type-specific temporal changes in neuroplasticity provide neurobiological evidence for the clinical observation that chronic pain is not simply the prolonged persistence of acute pain.
