Schematic of proposed mechanisms behind S1P-mediated hyperalgesia.

<p>Carrageenan injection leads to the activation of sphingosine kinase enzymes favoring the conversion of sphingosine to bioactive S1P. S1P then goes on to activate S1PR₁, initiating neutrophilic recruitment to the site of injury. Once there, neutrophils release several mediators known to sensitize nociceptors which induce peripheral sensitization and hyperalgesia.