Johns Hopkins School of Medicine

Molecular and Cellular Mechanisms of Pain Sensation

The Caterina lab studies mechanisms underlying neuropathic and inflammatory pain, predominantly using mice as a model system.  We employ 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 the complementary application of these approaches, and in collaboration with multiple laboratories, we seek to understand the cell types and molecules that contribute to the pathological sensation of pain, with the goal of guiding improvements in pain therapy.  

 Pain Mechanisms in Hereditary Palmoplantar Keratodermas

Hereditary Palmoplantar Keratodermas (PPK) are a heterogeneous group of rare disorders characterized by thickening of the epidermis on the palms of the hand and soles of the feet.  Mutations in any of at least 25 different genes can result in PPK.  In some, but not all patients with hereditary PPK, pain at the site of lesions is a prominent symptom, and is very difficult to treat.  Using mouse models of human hereditary PPKs, we seek to identify specific molecular and cellular mechanisms that lead to enhanced pain sensitivity in PPK lesions. Through these efforts, we hope to identify therapeutic targets for improved treatment of pain in PPK and also to define novel mechanisms that might be relevant to other, more common pain disorders.

Cellular and Molecular Mechanisms of Neuropathic Pain

Peripheral nerve injury, whether due to traumatic, metabolic, infectious, or toxic causes, often results in abnormally enhanced pain sensitivity known as neuropathic pain.  Using an array of surgical nerve injury models, we seek to understand the complex interplay between injured neurons, uninjured neurons, and nonneuronal cells (e.g. immune cells, keratinocytes, glial cells) that produce neuropathic pain and to understand how the processes of nerve regeneration and collateral sprouting, two additional consequences of nerve injury, influence and are influenced by pathological pain mechanisms.

Synthetic Biology Approaches to Treat Pathological Pain

One hallmark of many inflammatory and neuropathic pain mechanisms is an imbalance between signal transduction pathways that augment the sensitivity of nociceptive neurons and those that attenuate that sensitivity.  Using a synthetic biology approach, we are seeking to develop genetically encoded “smart” systems that produce analgesia only during times of excess pro-nociceptive signaling.  These systems, which are triggered by common pathological signaling processes such as receptor tyrosine kinase hyperfunction or elevated intracellular calcium, may prove beneficial not only in the setting of pathological pain but also in other disease states where such pathways are hyperactive.