About

Michael Caterina MD, PhD, is the Solomon H. Snyder Professor of Neurosurgery and a Professor of Neuroscience at Johns Hopkins School of Medicine. He is also the Director of the Neurosurgery Pain Research Institute. His research focuses on understanding the mechanisms underlying neuropathic and inflammatory pain, primarily using mice as a model system. His lab employs a wide array of methods, including mouse pain behavioral assays, sensory neuroanatomy, in vitro and in vivo neuronal imaging and electrophysiology, cell culture, biochemistry, transcriptomic analysis, and CAS9/Crispr mouse mutagenesis. Through these approaches and collaborations, he aims to identify the cell types and molecules that contribute to the pathological sensation of pain, with the goal of guiding improvements in pain therapy. His work also includes studying pain mechanisms in hereditary palmoplantar keratodermas (PPK), a group of rare disorders characterized by thickening of the epidermis on the palms and soles, with some patients experiencing prominent and difficult-to-treat pain. Using mouse models of human hereditary PPKs, he seeks to identify molecular and cellular mechanisms that lead to enhanced pain sensitivity in PPK lesions, aiming to find therapeutic targets for pain treatment and to uncover mechanisms relevant to other pain disorders. Additionally, his research addresses the cellular and molecular mechanisms of neuropathic pain resulting from peripheral nerve injury, exploring the interactions between injured neurons, uninjured neurons, and non-neuronal cells such as immune cells, keratinocytes, and glial cells. He also investigates how nerve regeneration and collateral sprouting influence pain mechanisms. Furthermore, Dr. Caterina's lab employs synthetic biology approaches to develop genetically encoded 'smart' systems that produce analgesia during times of excess pro-nociceptive signaling. These systems are triggered by pathological signaling processes like receptor tyrosine kinase hyperfunction or elevated intracellular calcium, with the potential to treat pathological pain and other diseases characterized by hyperactive signaling pathways.

Research topics

• Neuroscience
• Biology
• Medicine

Selected publications

• Genetic identification of mouse trigeminal afferents responsible for mechanical allodynia

  Cell Reports · 2026-01-01

  articleOpen access

  imaging shows that Piezo2 bcKD reduces not only hypersensitivity to low-force mechanical stimulation, mostly among medium-sized neurons, but also, unexpectedly, TNI-induced spontaneous activity. Therefore, Fos is useful for genetic labeling and manipulation of BA TG neurons. Furthermore, innocuous mechanical stimuli activate multiple TG afferent subtypes after TNI, possibly accounting for the complexity of resulting painful symptoms.

  PublisherDOI

• Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and calcium

  Journal of Biological Chemistry · 2025-01-14 · 3 citations

  articleOpen access

  Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for PKA and extracellular signal-regulated kinase (ERK) by (i) increasing KTR size, which reduces the confounding effect of KTR diffusion through the nuclear pore and (ii) modulating the strength of the bipartite nuclear localization signal in their kinase sensor domains, to ensure that the relative distribution of the KTR between the nucleus and cytoplasmic is determined by active nuclear import, active nuclear export, and relative activity of their cognate kinase. The resultant sets of ePKA-KTRs and eERK-KTRs display high sensitivity, broad dynamic range, and cell type-specific tuning. Moreover, co-expression of optically separable ePKA-KTRs and eERK-KTRs allowed us to simultaneously monitor the activation and inhibition of PKA and ERK, together with calcium levels, in live cells. These eKTRs responded as expected to direct agonists and inhibitors, and also confirmed that crosstalk between the PKA and ERK pathways is highly unbalanced, with the activation of PKA suppressing ERK activity, while activation of ERK induces PKA activity. Taken together, our findings highlight the importance of KTR size and bipartite nuclear localization signal strength to KTR sensitivity and dynamic range, show that different cell types require different eKTRs, and identify ePKA-KTR1.4 and eERK-KTR1.2 as particularly well-suited for monitoring PKA and ERK in primary sensory neurons.

  PublisherOA PDFDOI

• Postamputation pain: a multidisciplinary review of epidemiology, mechanisms, prevention, and treatment

  Regional Anesthesia & Pain Medicine · 2025-02-01 · 12 citations

  reviewOpen access

  Despite humanity's long experience with amputations, postamputation pain remains a highly prevalent, incompletely understood, and clinically challenging condition. There are two main types of postamputation pain: residual limb pain (including but not limited to the "stump") and phantom limb pain. Despite considerable overlap between the two, they also have distinct clinical features, risk factors, and pathophysiological mechanisms. Central, peripheral, and spinal mechanisms may all contribute to the protean manifestations of persistent postamputation pain; an improved understanding of these mechanisms will be essential to identify the most promising interventions for the prevention and treatment of postamputation pain. Although there are currently no standardized prevention or treatment recommendations for any type of postamputation pain, an evidence-based, multimodal strategy including pharmacological agents, nonsurgical procedures, surgery, complementary and integrative techniques, and assistive technologies may prevent the development of chronic postamputation pain after amputation and/or optimize treatment outcomes.

  PublisherOA PDFDOI

• Conditioned medium from painful non-NF2 schwannomatosis tumors increases pain behaviors in mice

  Scientific Reports · 2025-05-06 · 4 citations

  articleOpen access

  The majority of non-NF2 schwannomatosis (non-NF2 SWN) patients experience debilitating pain. Yet, it is not known why only some schwannomas cause pain or whether mutations in SWN-related genes, (SMARCB1 or LZTR1) differentially influence pain signaling pathways. Here, we established cell lines from non-NF2 SWN tumors resected from patients with varying degrees of pain and bearing mutations in different SWN-related genes. Compared with conditioned medium (CM) collected from "nonpainful" SWN tumors, CM from "painful" SWN tumors contained elevated levels of specific inflammatory cytokines (IL-6, IL-8, VEGF), and was able to enhance sensory neuron responsiveness to noxious TRPV1 and TRPA1 agonists in vitro. In in vivo studies, injection of CM from painful non-NF2 SWN into the hind paws of healthy mice evoked both more acute pain behavior and greater enhancement of mechanical stimulus-evoked behavioral responses than did CM from nonpainful non-NF2 SWN. Furthermore, the behavioral effects of painful CM differed as a function of the SWN-related gene mutations identified in the tumors of origin. Painful SMARCB1 mutant CM, for example, sensitized mice to mechanical stimulation at low forces, compared to non-painful tumor CM and control media, but this effect waned over time. In contrast, CM from a painful tumor with no detectable germline mutation in NF2, SMARCB1 or LZTR1 caused the greatest increase in responsiveness to low mechanical forces and this effect lasted for 2 days post-injection. These experiments establish a paradigm for examining the mechanisms by which painful SWN tumors bearing different mutations produce their sensory effects and will thus facilitate better understanding and, potentially, treatment of the pain endured by non-NF2 SWN patients.

  PublisherOA PDFDOI

• CTIM-22. WINDOW OF OPPORTUNITY STUDY OF NIVOLUMAB AND IPILIMUMAB IN PEOPLE WITH NEUROFIBROMATOSIS TYPE 1 AND NEWLY DIAGNOSED MALIGNANT AND PRE-MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

  Neuro-Oncology · 2025-11-01

  articleOpen access

  Abstract Neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with no curative medical therapies. Most clinical trials target recurrent or refractory disease, leaving a critical gap in early-stage treatment strategies. Given the immunogenic potential of MPNST and the need for innovative trials for this rare and fatal peripheral nervous system cancer, we conducted a multi-center study to assess the safety and feasibility of initiating neoadjuvant immunotherapy with nivolumab and ipilimumab immediately after diagnosis, prior to standard-of-care (SOC) therapy. Participants aged 12 years or older with NF1 and newly diagnosed atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) or MPNST, planned for surgical resection, were enrolled across four sites. Within one week of diagnostic biopsy, patients received nivolumab (4.5 mg/kg IV) and ipilimumab (1 mg/kg IV) x two doses administered three weeks apart. This was followed by institution-specific SOC therapy (encompassing surgery, cytotoxic chemotherapy, radiation). Pharmacodynamic and immunologic biomarkers are being evaluated in serial blood samples and paired tumor samples for immune profiling including tumor-infiltrating lymphocytes and neoantigen-specific T cell clones. The primary endpoint was feasibility, defined by at least 60% of participants completing both doses and initiating SOC therapy within 8 weeks of biopsy tissue diagnosis. Of the 11 currently evaluable patients (1 ANNUBP, 10 MPNST, median age 35, 42% female), 10 met this benchmark (90%). Five participants continued nivolumab during SOC therapy. Adverse events were mostly mild (one dose-limiting toxicity) and often overlapped with expected SOC AE profiles. No participant discontinued treatment due to adverse events. Six patients (55%) experienced disease progression (PFS 4–12 months), and four have died (OS 9–31 months). These results demonstrate that early administration of nivolumab and ipilimumab is feasible and tolerable in people with NF1-associated MPNST and may provide a platform for future immune-based therapeutic strategies in this high-risk population.

  PublisherOA PDFDOI

• Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma

  Journal of Neuroscience · 2024-06-12 · 1 citations

  articleOpen accessSenior author

  SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss-of-function mutations in SLURP1 lead to a rare autosomal recessive palmoplantar keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as pachyonychia congenita and Olmsted syndrome show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knock-out and Slurp2X knock-out, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals includes augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed slightly reduced glabrous skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knock-out mice. Primary sensory neurons innervating hindpaw glabrous skin from Slurp2X knock-out mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knock-out mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain.

  PublisherOA PDFDOI

• The nociceptive activity of peripheral sensory neurons is modulated by the neuronal membrane proteasome

  Cell Reports · 2024-04-01 · 9 citations

  articleOpen access

  signaling induced by KCl depolarization, αβ-meATP, or the pruritogen histamine. Taken together, these data support a model whereby NMPs are expressed on a subset of somatosensory DRGs to modulate signaling between neurons of distinct sensory modalities and indicate the NMP as a potential target for controlling pain.

  PublisherDOI

• Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and Ca ²⁺

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-02 · 2 citations

  preprintOpen access

  Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) that display high sensitivity, rapid response kinetics, broad dynamic range, cell type-specific tuning, and an ability to detect PKA and ERK activity in primary sensory neurons. Moreover, co-expression of optically separable eKTRs for PKA and ERK revealed the kinetics of expected and unexpected crosstalk between PKA, ERK, protein kinase C, and calcium signaling pathways, demonstrating the utility of eKTRs for live cell monitoring of diverse and interacting signaling pathways. These results open the door to improved live-cell and in vivo measurements of key signaling pathways in neurons, while at the same time demonstrating the importance of KTR size and NLS strength to KTR dynamics.

  PublisherDOI

• Pain in the Context of Sensory Deafferentation

  Anesthesiology · 2024-03-08 · 15 citations

  article

  Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.

  PublisherDOI

• Conditioned medium from painful schwannomatosis tumors increases pain behaviors in mice

  Research Square · 2024-04-19

  preprintOpen access

  Abstract The majority of schwannomatosis (SWN) patients experience debilitating pain. Yet, it is not known why only some schwannomas cause pain or whether mutations in SWN-related genes, (SMARCB1 or LZTR1) differentially influence pain signaling pathways. Here, we established cell lines from SWN tumors resected from patients with varying degrees of pain and bearing mutations in different SWN-related mutations. Compared with conditioned medium (CM) collected from “nonpainful” SWN tumors, CM from “painful” SWN tumors contained elevated levels of specific inflammatory cytokines (IL-6, IL-8, VEGF), and was able to enhance sensory neuron responsiveness to noxious TRPV1 and TRPA1 agonists in vitro. In in vivo studies, injection of CM from painful SWN into the hind paws of healthy mice evoked both more acute pain behavior and greater enhancement of mechanical stimulus-evoked behavioral responses than did CM from nonpainful SWN. Furthermore, the behavioral effects of painful CM differed as a function of the SWN-related gene mutations identified in the tumors of origin. Painful SMARCB1 mutant CM, for example, sensitized mice to mechanical stimulation at low forces, compared to non-painful tumor CM and control media, but this effect waned over time. In contrast, CM from a painful tumor with no detectable mutation in either SMARCB1 or LZTR1 caused the greatest increase in responsiveness to low mechanical forces and this effect lasted for 2 days post-injection. These experiments establish a paradigm for examining the mechanisms by which painful SWN tumors bearing different mutations produce their sensory effects and will thus facilitate better understanding and, potentially, treatment of the pain endured by SWN patients.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DE022750

  NIH · $3.5M · 2017

• NIH Grant R21AR062826

  NIH · $392k · 2014

• NIH Grant R01NS054902

  NIH · $1.2M · 2012

• NIH Grant R01NS051551

  NIH · $1.6M · 2011

Frequent coauthors

• Lintao Qu

  First Hospital of China Medical University

  38 shared

• Peter N. Devreotes

  Johns Hopkins University

  36 shared

• Xinzhong Dong

  Johns Hopkins Medicine

  34 shared

• Thomas J. Rogers

  27 shared

• Sadeet Inan

  National Cancer Institute

  27 shared

• Joost J. Oppenheim

  Center for Cancer Research

  27 shared

• Jiming Wang

  Southern University of Science and Technology

  25 shared

• Ronghua Sun

  Beijing National Laboratory for Molecular Sciences

  25 shared

Labs

• Michael Caterina's LabPI

  The lab webpage does not provide a description of the research focus.

Education

• M.D.

  Johns Hopkins University School of Medicine

• Ph.D.

  Johns Hopkins University School of Medicine