Glial Modulation of Pain: A Step Beyond

Role of RVM glial cells in facilitatory descending pain pathway. Schematic representation of the classical and novel elements present in RVM proposed to be involved in the descending facilitation of pain transmission during neuropathic pain. The nociceptive information arises from the peripheral nociceptive system through trigeminal nucleus by means of a specific tract. This continuous information induces a direct or indirect (via other encephalic structures) release of neurotransmitters (ATP, CCK, BNDF, SP, glutamate, and fractalkine, etc.) in the RVM. These substances could produce an intense activation of microglial cells that in turn produce IL-18 (Miyoshi et al., 2008). IL-18 seems to mediate the interaction between activated microglia and astrocytes. After activation, astrocytes produce and release cytokines such as TNF-α and IL-1β. These cytokines, acting on specific receptors expressed by a subtype of RVM neurons (on-cells), modulate the facilitatory descending pain pathway through enhancement of glutamatergic transmission.