Figure 3.

Schematic summarizes the organization of several dorsal horn systems that contribute to the processing of nociceptive information. Primary afferent C fibers release peptide (e.g., sP/CGRP, etc.) and excitatory amino acid (glutamate) products. Small DRG as well as some postsynaptic elements contain NOS) and are able on depolarization to release NO. Peptides and excitatory amino acids evoke excitation in second-order neurons. For glutamate, direct monosynaptic excitation is mediated by non-NMDA receptors (i.e., acute primary afferent excitation of WDR neurons is not mediated by the NMDA or NK-1 receptor). Interneurons excited by afferent barrage induce excitation in second-order neuron via a NMDA receptor, which leads to an increase in intracellular Ca²⁺, activation of phospholipase A2, NOS, and phosphorylating enzymes. COX products (PG) and NO are formed and released. These agents diffuse extracellularly and facilitate transmitter release (retrograde transmission) from primary and nonprimary afferent terminals by either a direct cellular action (e.g., NO) or by an interaction with a specific class of receptors [e.g., PG type E (EP) receptors for prostanoids]. Phosphorylation of intracellular protein (e.g., enzymes and receptors such as NMDA) leads to additional enhanced sensitivity. See text for other details.