Scholars@Duke
Christopher Donnelly

Christopher Donnelly

Assistant Professor in Anesthesiology
Anesthesiology
christopher.donnelly@duke.edu
DUMC 3094, MS #50, Durham, NC 27710
3 Genome Ct. MSRB3 Rm #6142, Durham, NC 27710

Selected Publications

Clinical and biobehavioral phenotypic assessments and data harmonization for the RE-JOIN research consortium: Recommendations for common data element selection.

Journal Article Neurobiol Pain · 2024 BACKGROUND: The Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium is part of the Helping to End Addiction Long-term® (HEAL) Initiative. HEAL is an ambitious, NIH-wide initiative to speed scientific solutions to stem the national opioi ... Full text Link to item Cite

PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.

Journal Article Neuron · September 6, 2023 Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentia ... Full text Link to item Cite

Toll-Like Receptors in Pain and Itch

Chapter · January 1, 2023 Pattern recognition receptors (PRR) are genetically encoded proteins which recognize a host of highly conserved “danger signals” produced by microbial organisms (pathogen-associated molecular patterns, or PAMPs) or released by damaged host cells (damage-as ... Full text Cite

Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition.

Journal Article Cell Tissue Res · February 2022 The fungiform papilla (FP) is a gustatory and somatosensory structure incorporating chorda tympani (CT) nerve fibers that innervate taste buds (TB) and also contain somatosensory endings for touch and temperature. Hedgehog (HH) pathway inhibition eliminate ... Full text Link to item Cite

IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice.

Journal Article Neuron · September 1, 2021 Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling is not well studied. Here we report that administration of IL-23 produces mechanical pain (mechanical allodynia) in female but not male mice, ... Full text Link to item Cite

STING suppresses bone cancer pain via immune and neuronal modulation.

Journal Article Nat Commun · July 27, 2021 Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immun ... Full text Link to item Cite

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Journal Article Nat Commun · March 17, 2021 GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia fol ... Full text Link to item Cite

STING controls nociception via type I interferon signalling in sensory neurons.

Journal Article Nature · March 2021 The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplas ... Full text Link to item Cite

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.

Journal Article Pain Rep · 2021 Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide saf ... Full text Link to item Cite

Cancer-specific type-I interferon receptor signaling promotes cancer stemness and effector CD8+ T-cell exhaustion.

Journal Article Oncoimmunology · 2021 Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility ... Full text Link to item Cite

Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons.

Journal Article Sci Rep · December 17, 2020 During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes dramatic axon g ... Full text Link to item Cite

PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.

Journal Article iScience · October 23, 2020 The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, ... Full text Link to item Cite

How Do Sensory Neurons Sense Danger Signals?

Journal Article Trends Neurosci · October 2020 Sensory neurons are activated by physical and chemical stimuli, eliciting sensations such as temperature, touch, pain, and itch. From an evolutionary perspective, sensing danger is essential for organismal survival. Upon infection and injury, immune cells ... Full text Link to item Cite

Plasma membrane localization of the GFL receptor components: a nexus for receptor crosstalk.

Journal Article Cell Tissue Res · October 2020 The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) comprise a group of four homologous and potent growth factors that includes GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN). The survival, growth, and mitotic activit ... Full text Link to item Cite

PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.

Journal Article J Clin Invest · July 1, 2020 Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruc ... Full text Link to item Cite

Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain.

Journal Article Neurotherapeutics · July 2020 The current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve sti ... Full text Link to item Cite

Central Nervous System Targets: Glial Cell Mechanisms in Chronic Pain.

Journal Article Neurotherapeutics · July 2020 Interactions between central glial cells and neurons in the pain circuitry are critical contributors to the pathogenesis of chronic pain. In the central nervous system (CNS), two major glial cell types predominate: astrocytes and microglia. Injuries or pat ... Full text Link to item Cite

Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons.

Journal Article Curr Opin Neurobiol · June 2020 Inflammation is the body's protective reaction to injury and infection. Pain is a hallmark of inflammation and can be either protective or detrimental during acute or chronic phase. Macrophages play a chief role in the pathogenesis of pain and have bilater ... Full text Link to item Cite

HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING.

Journal Article J Clin Invest · April 1, 2020 The incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surpassed that of cervical cancer and is projected to increase rapidly until 2060. The coevolution of HPV with transforming epithelial cells leads to th ... Full text Link to item Cite

Astrocytes in chronic pain and itch.

Journal Article Nat Rev Neurosci · November 2019 Astrocytes are critical for maintaining the homeostasis of the CNS. Increasing evidence suggests that a number of neurological and neuropsychiatric disorders, including chronic pain, may result from astrocyte 'gliopathy'. Indeed, in recent years there has ... Full text Link to item Cite

Scratching after Stroking and Poking: A Spinal Circuit Underlying Mechanical Itch.

Journal Article Neuron · September 25, 2019 Mechanical itch is a desire to scratch due to light mechanical stimuli. In this issue of Neuron, Pan et al. (2019) identify a feedforward inhibition circuit in the spinal cord dorsal horn that processes mechanical itch as well as spontaneous itch. ... Full text Link to item Cite

Head and Neck Cancer Immunotherapy beyond the Checkpoint Blockade.

Journal Article J Dent Res · September 2019 The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients wi ... Full text Link to item Cite

Ret Signaling Is Required for Tooth Pulp Innervation during Organogenesis.

Journal Article J Dent Res · June 2019 During organogenesis, the timing and patterning of dental pulp innervation require both chemoattractive and chemorepellent cues for precise spatiotemporal regulation. Our understanding of the signaling mechanisms that regulate tooth innervation during deve ... Full text Link to item Cite

Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck.

Journal Article Oral Oncol · December 2018 INTRODUCTION: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavio ... Full text Link to item Cite

Non-canonical Ret signaling augments p75-mediated cell death in developing sympathetic neurons.

Journal Article J Cell Biol · September 3, 2018 Programmed cell death (PCD) is an evolutionarily conserved process critical in sculpting many organ systems, yet the underlying mechanisms remain poorly understood. Here, we investigated the interactions of pro-survival and pro-apoptotic receptors in PCD u ... Full text Link to item Cite

Mitigating SOX2-potentiated Immune Escape of Head and Neck Squamous Cell Carcinoma with a STING-inducing Nanosatellite Vaccine.

Journal Article Clin Cancer Res · September 1, 2018 Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape.Experimental Design: We performed RNA-Seq of sensitive and resista ... Full text Link to item Cite

Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification.

Journal Article Proc Natl Acad Sci U S A · January 16, 2018 The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study ... Full text Link to item Cite

p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling.

Journal Article Cell Rep · October 17, 2017 Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly un ... Full text Link to item Cite