Abstract| Volume 14, ISSUE 4, SUPPLEMENT , S54, April 2013

Nociceptor activity is altered in Group II mGluR knock-out rats

      Previous studies from our laboratory demonstrate that Group II metabotropic glutamate receptors (mGluRs) are expressed by peripheral nociceptors and their activation inhibits pain behaviors and nociceptor activity in the inflamed state. We obtained Group II mGluR2 KO and WT rats from Transposagen to further elucidate the role of these receptors in pain transmission. We recorded from identified nociceptors using our in vitro skin-nerve preparation. The glabrous skin of the hindpaw is dissected free keeping the plantar nerves intact. The nerves are teased apart to isolate single units for recording. The receptive field of each unit is defined and responses to heat, mechanical and mustard oil (1μm, TRPA1 agonist) are determined. The data shows that the background discharge rate in KO rats (0.35±0.08 imp/s, n=13) is significantly increased compared to WT (0.11±0.04 imp/s, n=10). Furthermore, application of 1 μM mustard oil induces a significant increase in discharge rate in KO (1.19±0.26 imp/s, n=13) compared to WT rats (0.68±0.12 imp/s, n=10). However, the responses to heat and mechanical simulation are not significantly different in KO vs. WT (no change in threshold or discharge rate). We have previously shown that Group II mGluR2s do not maintain a tonic inhibitory control over nociceptors thus the increase in background activity in the absence of the receptors is unexpected. Our behavioral data demonstrate the KO rats have an increase in nocifensive behaviors in response to MO applied to the hindpaw and this data confirms these findings at the single fiber level. The data suggest that Group II receptors negatively modulate TRPA1 in the naïve state and loss of this control produces enhanced responses to a TRPA1 agonist.