Activation of Central Terminal Vanilloid Receptor-1 Receptors and αβ-Methylene-ATP-Sensitive P2X Receptors Reveals a Converged Synaptic Activity onto the Deep Dorsal Horn Neurons of the Spinal Cord

Abstract

Using a spinal cord slice preparation and patch-clamp recordings from spinal cord dorsal horn neurons, we examined excitatory and inhibitory circuits connecting to lamina V neurons after the activation of afferent central terminal vanilloid receptor-1 (VR1) receptors and P2X receptors. We found that single neurons in lamina V often received excitatory inputs from two chemically defined afferent pathways. One of these pathways was polysynaptic from capsaicin-sensitive afferent terminals. In this pathway the capsaicin-sensitive afferent input first activated interneurons in superficial laminas, and then the excitatory activity was transmitted onto lamina V neurons. The second excitatory input was monosynaptic from alpha(beta)m-ATP-sensitive/capsaicin-insensitive afferent terminals. Both capsaicin-sensitive and alpha(beta)m-ATP-sensitive/capsaicin-insensitive pathways also recruited polysynaptic inhibitory inputs to lamina V neurons. Furthermore, we demonstrated that simultaneous activation of both capsaicin-sensitive afferent pathways and alpha(beta)m-ATP-sensitive/capsaicin-insensitive pathways could generate a temporal summation of excitatory inputs onto single lamina V neurons. These convergent pathways may provide a mechanism of sensory integration for two chemically defined sensory inputs and may have implications in different sensory states.

Purinergic P2X receptors facilitate inhibitory GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

“…The increases due to α, β-methylene ATP on inhibitory neurotransmission to CVNs was blocked by the P2X receptor antagonist TNP-ATP, further indicating facilitation of inhibitory neurotransmission to CVNs results from P2X but not P2Y receptors. This is congruent with the increased spontaneous IPSC frequency elicited by α, β-methylene ATP in lamina V neurons mediated by glycinergic/GABAergic inputs from dorsal horn interneurons (Nakatsuka et al, 2002).…”

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

“…As the present and other studies have shown, the primary afferent neurons express both P2X 2 and P2X 3 receptors. In vitro studies in the spinal dorsal horn have show that the P2X receptor agonist α ,β-meATP causes an increase in glutamatergic (Nakatsuka and Gu, 2001;Nakatsuka et al, 2002;Nakatsuka et al, 2003;Tsuzuki et al, 2003). We have reported analogous results in the medullary dorsal horn (Jennings et al, 2006).…”

“…In the spinal somatosensory system, all P2X receptor subtypes with the exception of P2X 7 are expressed in the spinal dorsal horn, the dorsal root ganglion (DRG), and the central terminals of primary afferent neurons (Burnstock, 2000;Khakh, 2001;North, 2002). In vivo and in vitro electrophysiological recordings from single dorsal horn neurons have implicated P2X receptors on primary afferent terminals in spinal nociceptive transmission (Nakatsuka and Gu, 2001;Nakatsuka et al, 2002;Nakatsuka et al, 2003; Correspondence details: Dr. Ernest Jennings Dept. Anatomy & Cell Biology The University of Melbourne Parkville, Victoria, 3010, Australia Tel: +61 3 8344 5802 Fax: +61 3 9347 9619 Email: e.jennings@unimelb.edu.au.…”

Purinergic and Vanilloid Receptor Activation Releases Glutamate from Separate Cranial Afferent Terminals in Nucleus Tractus Solitarius

“…One third or more dorsal root neurons, the source for those dorsal horn afferent terminals, respond to both CAP and ATP , although proportions vary across reports (Oh et al, 2001;Petruska et al, 2002;Labrakakis et al, 2003). Activation of P2X receptors in nearly all dorsal horn neurons transiently increases glutamate release , and most lamina II dorsal horn neurons are CAP sensitive (Nakatsuka et al, 2002). However, many P2X-sensitive afferent terminals in lamina V are CAP resistant .…”