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. Author manuscript; available in PMC: 2010 Jan 1.
Published in final edited form as: Annu Rev Neurosci. 2009;32:1–32. doi: 10.1146/annurev.neuro.051508.135531

Table 1. Immune modulators of neuropathic pain.

Drug Mechanism of action Effect in preclinical neuropathic models Review/reference
Minocycline Tetracycline antibiotic. Immunosuppression in part mediated through p38 inhibition. Inhibits microglial activation. Reduces tactile allodynia most effectively when treatment begins prior to nerve injury Mika 2008
Phosphodiesterase inhibitors (Propentofylline, AV-411, Pentoxifylline) Nonselective phosphodiesterase inhibitors Reduce mechanical allodynia by suppressing microglial and astrocyte activity. Often associated with a decrease in proinflammatory cytokines Mika 2008
Methotrexate Reduces folate, blocks de novo purine and thymidylate synthesis Inhibits microglial activation and proliferation. Most effective when given early after nerve injury Scholz et al. 2008
Nucleotide receptor antagonists Activation of P2X and P2Y receptors modulates the activity of peripheral immune cells and microglia Block the activation of peripheral macrophages and spinal microglia Inoue et al. 2007
p38 MAP kinase inhibitors Inhibit important signaling pathways in microglial cells Reduce tactile allodynia. Most effective when treatment begins prior to nerve injury Ji & Suter 2007
Modulators of cytokine synthesis and activity Neutralizing antibodies and receptor-trapping strategies directed against IL1, IL6, IL10, TNF, and others Reduce the biological effects of proinflammatory cytokines. IL10 has antiinflammatory activity Mika 2008,Watkins et al. 2007
Complement inhibitors Block activation of complement factors expressed by microglia Inhibition of complement pathways including the activation of C5, which acts as an immune cell chemoattractant in the spinal cord dorsal horn Mika 2008
Cannabinoids Activates the CB2 receptor, which is expressed predominantly on microglia CB2 regulates immune cell proliferation and migration. CB2 agonists reduce mechanical allodynia Romero-Sandoval et al. 2008