Fig. 10

Schematic proposition of the mechanisms involved in L. amazonensis infection-induced spinal cord events leading to hyperalgesia in BALB/c mice. The peripheral infection with L. amazonensis leads to an immune reaction in infected paw tissue characterized by neutrophil recruitment (increased MPO activity) and elevated production of pro-inflammatory cytokines TNF-α and IL-1β at the primary infection focus, which are well-known sensitizers of first-order neurons. Nociceptive signaling reaches the dorsal horn of spinal cord resulting in increased mRNA expression of CX₃CL1, CX₃CR1, microglia, and astrocytes activation and consequent NFκB-dependent TNF-α and IL-1β increased mRNA expression. These pathological modifications in spinal cord sites in response to L. amazonensis peripheral infection contributes therefore to the sensitization of first- and second-order neurons and maintenance of a hyperalgesic state in experimental leishmaniasis-induced pain