“…In the peripheral nervous system, classic inflammatory modulators are secreted by neutrophils in a more acute stage of neuroinflammation and then by macrophages and T cells after the persistence of inflammation sensitizes either the nociceptor sensory receptors ( Basbaum et al, 2009 ) or peripheral glial cells, such as Schwann cells and satellite glia cells ( Ellis and Bennett, 2013 ), to potentially noxious stimuli in primary afferent neurons, modulating pain sensitivity ( Ji R. R. et al, 2013 ). Infiltrating macrophages and Schwann cells can secrete proinflammatory cytokines, such as IL-1β and TNF-α ( Nathan, 1987 ; Palmer and Weaver, 2010 ), which is consistent with the increase in plasma proinflammatory cytokines in people suffering from chronic pain ( Vendrusculo-Fangel et al, 2019 ) and preclinical pain models ( Table 1 ). Both peripheral and central inflammation are associated with symptoms of pain and depression ( Walker et al, 2013b ), as characterized by dysregulation of the immune system ( Burke et al, 2014 ), neurotransmitters such as noradrenaline and serotonin ( Stahl and Briley, 2004 ; Goldenberg et al, 2010 ), neuropeptides such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) ( Kramer et al, 1998 ; Werner and Coveñas, 2010 ), oxidative stress ( Arora et al, 2011 ) and cytokines ( Wallace, 2006 ; Dowlati et al, 2010 ).…”