Purinergic and NMDA-Receptor Mechanisms Underlying Tooth Pulp Stimulation-Induced Central Sensitization in Trigeminal Nociceptive Neurons

摘要

Nociceptive neurons in spinal nociceptive pathways (e.g., the dorsal horn and ventrobasal thalamus) may undergo a prolonged period of increased excitability following injury or inflammation of spinally innervated tissues. These changes reflect a neuroplasticity or "central sensitization" of nociceptive neuronal circuits and represent important processes in the development of chronic pain (Ren and Dubner 1999; Vos et al. 2000; Ji and Woolf 2001). While NMDA-receptor mechanisms are critical to this central sensitization process, recent studies raise the possibility that purinergic receptor mechanisms involving adenosine triphosphate (ATP) and P2X receptor (P2XR) modulation of glutamate release from presynaptic nociceptive afferents in the central nervdus system also may play a role (MacDermott et al. 1999; McCleskey and Gold 1999; Burnstock 2000; Nakatsuka and Gu 2001). Seven P2XR subtypes have been cloned, and some occur as hetero-multimers (e.g., P2X_2/P2X_3R, P2X_1/P2X_5R, and P2X_4/P2X_6R). P2X_1R through P2X_6R are all expressed in neurons of sensory ganglia, and with the exception of P2X_3R, they are also found in dorsal and ventral regions of the spinal cord. P2X_2R, P2X_4R, and P2X_6R in particular are expressed within lamina II of the dorsal horn.