The Crawford lab uses a comparative neuroscience approach to understand how your sense of touch and your sense of pain are interrelated and how they dysfunction in the face of disease. Sensory neurons that mediate light touch (low threshold mechanoreceptors) may be as important as pain neurons (nociceptors) when it comes to mechanical allodynia, the condition where a stimulus that would usually feel like light touch feels very painful instead. We suspect certain types of touch neurons may play a unique role in other types of pain too, though the exact nature of that role is poorly understood.
The skin is a great example of how diverse sensory neurons can be, as there are over 15 subtypes of sensory neurons that innervate the skin, each having a different contribution to distinct modalities of sensation like the feeling of wind moving across the skin, a sharp pinprick, or heat from a warm surface.
Sensory afferents of the haired and glabrous skin. The distinct patterns of skin innervation by sensory neuron subtypes demonstrate the heterogeneity of the somatosensory nervous system. Crawford and Caterina, Toxicologic Pathology, In Press.
The diverse morphologic and physiologic feature of sensory neuron subtypes may underlie unique reactions to injury and, thus, unique roles in pathologic conditions. For this reason, we examine many different types of sensory neurons to elucidate cell-specific mechanisms of pain and peripheral neuropathies. We aim to identify specific molecules that are altered in our disease models, to determine which sensory neuron subtypes exhibit these changes, and to evaluate this pattern of changes across different disease conditions to assess the relevance of our findings. Our transgenic mouse lines have subtypes of sensory neurons that express fluorescent markers or silencing constructs so that we can visualize sensory neurons or manipulate their function. This enables behavioral tests of sensation using mice that model a disease process, as well as genetic, molecular, and neurophysiologic studies in tissues isolated from those same mice.
Confocal photomicrograph demonstrating the diversity of mouse DRG neurons. Immunofluorescent staining indicates the cytoplasmic expression of two molecular markers in green and red along with genetic labeling of a targeted subtype of touch neuron in blue. Neurons that are co-labeled in this image appear yellow, teal, or white. Scale bar is 100 µm. Crawford and Caterina, Toxicologic Pathology, In Press.
We are excited to build upon our mouse models with comparative studies in other species to discover what mice can teach us about sensory neural dysfunction in both human and animal patients with complex diseases. Comparative approaches in the lab evaluate cell-specific changes in molecular markers and microscopic anatomy in tissues from other species, including biopsy and post-mortem samples from veterinary patients.
The potential impact of our research
The pain mechanisms we highlight can provide novel targets for developing preventative, disease-modifying, or therapeutic drugs that are effective across several species during preclinical and clinical trials. Mechanistic understanding of comparative pain pathways will also enable us to determine which emerging pain therapies developed for human patients will be well suited for veterinary patients with various types of disease. Finally, by clarifying how these mechanisms relate to histopathologic and behavioral endpoints, we hope to improve diagnostics for both veterinary and human patients.