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. Author manuscript; available in PMC: 2014 Apr 10.
Published in final edited form as: Neuron. 2013 Mar 21;78(1):138–151. doi: 10.1016/j.neuron.2013.01.030

Figure 7. Tonic and evoked activity in icilin (cold)-responsive spinal neurons is enhanced after ablating CGRPα DRG neurons.

Figure 7

(A–F) Patch recordings of lamina II spinal neurons from saline-treated and DTX-treated CGRPα-DTR+/− mice (4 weeks old). Sagittal lumbar spinal cord slices harvested 3 days after last saline/DTX treatment. Picospritzer filled with drugs at the indicated concentrations then pressure ejected near the recorded neuron. (A) Example recordings, (C) EPSC event histogram and (E) EPSC frequency in capsaicin-responsive spinal neurons. (B) Example recordings, (D) EPSC event histogram (F) EPSC frequency in icilin-responsive spinal neurons. Number of neurons studied and their physiological classification are shown in Table S1. T test relative to saline-treated; *p<0.05, **p<0.005, ***p<0.0005. (G) Somatosensory circuits before and (H) after ablation suggests central disinhibition mechanism for enhanced cold sensitivity. CGRP-IR neurons are myelinated (A-fibers) or unmyelinated (C-fibers) (Lawson et al., 2002) and ~50% express the capsaicin receptor TRPV1 (Cavanaugh et al., 2011; McCoy et al., 2012). As found in the present study, CGRPα neurons are selectively required to sense heat, capsaicin and some pruritogens (histamine=hist and CQ) and, via an interneuron, tonically inhibit cold-responsive postsynaptic spinal neurons. The existence of this inhibitory interneuron that monosynaptically connects capsaicin-responsive spinal neurons with icilin-responsive spinal neurons was demonstrated by paired recordings (Zheng et al., 2010). Following CGRPα neuron ablation, tonic and evoked excitatory activity in cold-sensitive spinal neurons is enhanced. Ablation also enhanced cold and cold-mimetic sensitivity at the behavioral level. CGRPα neurons do not express TRPM8 and very few (2%) respond to icilin (McCoy et al., 2012). Cold/TRPM8+ neurons are either myelinated or unmyelinated (Cain et al., 2001; Kobayashi et al., 2005), and both subsets are present in CGRPα-neuron ablated mice. Activity in unmyelinated TRPM8+ afferents likely colors the perception of hot and cold temperatures with a “burning” sensation (Campero et al., 2009). TRPV1+ neurons are primarily unmyelinated (Lawson et al., 2008).