We are interested in defining the neural circuits and mechanisms that cause and maintain mechanical allodynia, a condition in which light touch or movement becomes painful after an injury. Ultimately, the goal is to translate our findings into new, non-addictive pain therapies.
Acute pain protects the body from injury. Some forms of persistent pain are also advantageous helping to protect wounded areas from further injury. However persistent pain can also become pathological and debilitating. Clinical level pain affects ~100 million people in the US and treatment options are still inadequate. Thus, a better understanding of the biology underlying pain will provide opportunities to identify improved therapies.
Persistent pain states arise from many different types of injuries and diseases and it is well-accepted that etiology must be considered to fully understand the molecular and cellular manifestation of pain. Our recent work demonstrates the existence of distinct dorsal horn mechanical allodynia circuits, which are differentially activated depending on the nature of the injury. Our goal is to fully map the dorsal horn mechanical allodynia circuits, including their relationship to primary afferents and descending inputs. We will use this information to explore mechanisms of induction and maintenance on a synaptic, cellular and molecular level. Our laboratory takes advantage of the many cutting-edge genetic tools available to probe neural circuits with high temporal and spatial resolution.
Strategies we use to test our hypotheses: • Optogenetics • Chemogenics • Retrograde tracing • High-resolution imaging • Whole-cell patch clamp recordings • Immunohistochemistry • Transgenic mice • In vivo viral expression • Pain behavior.
Peirs C, Williams S-PG, Zhao X, Walsh CE, Gedeon JY, Cagle NE, Goldring AC, Hioki H, Liu Z, Marell P and Seal RP. (2015) Dorsal Horn Circuits for Persistent Mechanical Pain. Neuron 87: 797-812. See Preview by Gangadharan and Kuner, Neuron 87:673-675.
Peirs C and Seal RP. (2015) Targeting Toll-like Receptors to Treat Chronic Pain. Nat. Med. 21(11).
Seal RP and Lumpkin EA. (2015) Cell Biology of Tactile Afferents. Affective Touch and the Neurophysiology of CT Afferents (Springer) In press
Honsek S, Seal RP, and Sandkühler J. (2015) Presynaptic Inhibition of Optogenetically Identified VGluT3+ Sensory Fibres by Opioids and Baclofen. Pain 156(2): 243-251.