Figure 6.

A model for explaining α_1E mutant phenotypes. Inflammatory mediators produced as a result of a chemical irritant injection stimulate primary afferent fibers, leading to excitation of the dorsal horn neurons. This information is further conveyed to supraspinal structures (e.g., thalamus). α_1E Ca²⁺ channel mediates either or both of these sensory transmissions in a gene-dosage-dependent manner. α_1E Ca²⁺ channel also mediates the descending antinociceptive signal by increasing the excitability of PAG neurons and/or by eliciting the release of an excitatory transmitter(s) from the terminals, which activate RM neurons. Serotonin released by the RM neurons in turn exerts inhibitory control on the spinal pain transmission.