TNF and Pain: There is limited evidence indicating that after RAGE and TLR4 activation, HMGB1 activates intracellular pathways such as c-Jun N-Terminal Kinase (JNK) and nuclear factor kappa B (NF-κB) (10), upregulating pro-inflammatory cytokines such as interferon-gamma (IFN-γ), interleukin-6 (IL-6), tumoral necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); which are involved in the genesis of neuropathic pain (6, 11, 12).