Mechanism of neuropathic pain in maxillofacial region and its association with inflammatory cytokines

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The current literature strongly implicates a role for proinflammatory cytokines such as interleukin (IL)-1 β and tumor necrosis factor-α in the genesis or maintenance of hyperalgesia. The cytokine cascade has emerged as an important contributor to the development of persistent pain states. Importantly, the involvement of cytokines in persistent pain does not appear to be limited to peripheral sensitization. Independent of release of cytokines from the periphery site of injury, inflammatory cytokines are induced in the central nerve system (CNS). IL-1 β is a prototype proinflammatory cytokine that is highly inducible in the CNS after injury. By acting on IL-1 receptors (IL-1R) that are present on neurons and glia, IL-1 β can activate distinct intracellular signaling pathways and influence cellular function. It has been shown that IL-1 β interacts with N-methyl-D-aspartate (NMDA) receptors through activation of Src family protein tyrosine kinases, leading to enhanced NMDA receptor function. The present study directly addresses the role of proinflammatory cytokines in orofacial pain mechanisms following the chronic constriction injury (CCI) of the infraorbital nerve (IN). We demonstrate that IL-1 beta is selectively activated in astroglia in the spinal trigeminal nucleus including the subnuclei interpolaris/caudalis (Vi/Vc) transition zone and caudal subnucleus caudalis (Vc), two important regions for processing of orofacial noxious input.In conclusion, CCI of IN induced a upregulation of IL-1 beta in the spinal trigeminal nucleus including the laminated Vc and Vi/Vc. Mechanical hyperalgesia and allodynia at orofacial region developed after the chronic constriction injury of infraorbital nerve. The upregulated IL-1 beta was selectively colocalized with GFAP, a marker for astrocytes. Intrathecal infusion of IL-1ra, the naturally occurring antagonist of IL-1R, prevented the development of hyperalgesia/allodynia in orofacial region.