Painful Neuron-Microglia Interactions in the Trigeminal Sensory System

Abstract

The trigeminal sensory system is unique in its innervation of structures specific to the orofacial area. Nocicep- tive trigeminal afferents are known to synapse with second-order neurons in the trigeminal subnucleus caudalis (Sp5C) in the brain stem. The activity of neurons within the Sp5C is responsible for the relay of nociceptive signals to higher brain centers. Recent evidence suggests that central sensitization may be fundamental to many trigeminal-specific painful neu- ropathies, including trigeminal neuralgia and migraine. Glia within the Sp5C are emerging as prime suspects in trigeminal central sensitization. In particular, microglial activation has been implicated in the development of neuropathic pain. It is possible that activated microglia release factors that alter the activity of second-order neurons or the synaptic activity of peripheral terminals within the Sp5C. Microglial activation has been characterized by changes in morphology, expression of membrane receptors and ion chan- nels, as well as alterations to cytokine and chemokine release. In addition, microglia have been studied in brain slice and dissociated culture where activation is characterized by changes to P2X receptor and potassium channel membrane cur- rents. However, little is known about resting and activated microglial membrane properties in the Sp5C and, furthermore, how these properties are affected following trigeminal nerve injury. This review summarizes the anatomical and patho- physiological importance of the Sp5C and focuses on recent studies on neurons and microglia in the trigeminal sensory system. The final part of the review aims to link important aspects of microglial membrane physiology with their potential role in chronic trigeminal pain conditions.