Acute inflammatory pain mechanisms in LPS paw-injected mice

LIBIA CATALINA SALINAS CASTELLANOS; GEORGINA ORIANA MINGOLO MALNATI; MAYRA MICAELA MONTES; MARIELA LACAVE; ROMINA DE LUCCA; CARINA WEISSMANN

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

SAIC

Animal models of inflammatory pain have used a number of different irritants injectedinto skin, paws, muscles, joints and visceral organs. These irritants include those thatproduce acute inflammatory pain. Lipopolysaccharide (LPS) is one of the most studiedpathogen-associated activator of inflammation. Subcutaneous administration of LPSinto the subplantar region of rodent hind paws elicits an acute localized inflammatoryreaction leading to swelling. Similar inflammatory reactions are elicited by other agentsas Carrageenan, Zymosan and formalin.Acid-sensing ion channels (ASICs) play important roles in pain conditions. MitTx-1 (atoxin that activates ASIC1) injected in the mouse paw has also been documented totrigger pain behavior in mice. So far however, ASIC1 has only been barely described inthe skin. We have previously analyzed the hindpaw injection of formalin to assess acutepain showing ASIC1 levels increased at the spinal cord, anterior cingulate cortex, anddorsal root ganglia after formalin injections.In this work, we analyzed LPS-paw injected mice to focus on localized acute pain andASIC1 involvement in pain perception. We employed a range of techniques: westernblot, immunohistochemistry, von Frey and the hot plate tests. Our initial analysisdemonstrated a heightened expression of ASIC1 in the hind paw following LPS-inducedinflammation (4-fold increase in LPS-injected versus PBS-injected, p=0.0031, Student`st-test). The inflammatory process was marked by observable signs such as swelling(20% increase within 4 hours), neutrophil infiltration, and increased sensitivity tomechanical stimuli (more than 5-fold increase in 50% von Frey threshold) and thermalstimuli (45% increase in latency times in the hot plate test).Collectively, our resultssuggest a significant presence of ASIC1 channels in the skin, contributing tomechanisms underlying pain perception. This insight introduces potential therapeuticinterventions for pain relief treatments.