tacrolimus and Neuralgia

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.

Topics: Animals; Cell Communication; Cell Proliferation; Female; Ganglia, Spinal; Hyperalgesia; Immunosuppressive Agents; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microglia; Neuralgia; Peripheral Nerve Injuries; Pregnancy; Sensory Receptor Cells; Sex Factors; Tacrolimus

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Cell Communication; Cells, Cultured; Female; Ganglia, Spinal; Genes, Reporter; Humans; Hyperalgesia; Imidazoles; Macrophage Activation; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuralgia; Neutrophil Activation; Oxidation-Reduction; Pyridines; Receptor, Angiotensin, Type 2; Sensory Receptor Cells; Skin; Tacrolimus; TRPA1 Cation Channel

Post-transplant complications are common among patients receiving immunosuppressive medications, including pain syndromes. Recently, a pain syndrome, calcineurin-inhibitor induced pain syndrome (CIPS) has been described. To our knowledge, this article is the second report of tacrolimus-associated CIPS, and the first report in the pediatric setting.

Topics: Adolescent; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Neuralgia; Postoperative Complications; Syndrome; Tacrolimus