Stimulation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor evokes mixed responses in nociceptive fibers of mouse glabrous skin

This study examined the contribution of AMPA receptors to peripheral nociception using teased plantar nerve attached to glabrous skin of male C57B/6 mice. Identified receptive fields were isolated using a plastic well. After measuring mechanical (MECH), heat and cold responses, serial 10X dilutions of AMPA ranging from 1 pM to 1 mM were pipetted into the well. Firing activity was collected over 2 min for each dilution. After a 2 min wash-out, MECH, heat, and cold responses were re-measured. A 50% increase or decrease in threshold or firing rate was considered significant. Sixteen of 40 fibers responded directly to AMPA. Five fibers displayed gradual increases in background firing over the total dose range (EC50 26.6 nM). Eleven fibers displayed bimodal distributions (EC50 11.3 pM and 3.0μM). AMPA effects on heat, cold and MECH responses were mixed. Before and after profiles measured in 34 fibers showed these changes: HEAT: 7 fibers more sensitive threshold; 5 less sensitive 7 fibers increased firing rate; 13 decreased COLD: 3 fibers more sensitive threshold; 8 less sensitive 12 fibers increased firing rate; 10 decreased MECH: 9 fibers more sensitive threshold; 4 less sensitive 13 fibers increased firing rate; 12 decreased Changes in the three modalities were independent, i.e., a change in one modality was not predictive of or correlated with changes in other modalities. All 34 fibers showed changes in at least one parameter. AMPA responsive nociceptive fibers represent mixed populations. The GluA2 subunit is a candidate for conferring differing response properties since this subunit blocks calcium permeability. Trafficking of GluA2 subunits changes the calcium permeability of the AMPA receptor and may change the responsiveness of AMPA-containing nociceptive fibers to heat, cold or mechanical stimulations. Future research using antagonists directed at GluA2-containing and GluA2-lacking AMPA receptors can elucidate these mechanics in nociceptive function.