Differential expression of the calcitonin receptor, CGRP and amylin in the trigeminal and dorsal root ganglia

Abstract text (incl. figure legends and references)

Objective: The trigeminal ganglia (TG) and dorsal root ganglia (DRG) are anatomically important sites for pain, containing neuropeptides and receptors that modulate pain transmission. The neuropeptides, calcitonin gene-related peptide (CGRP) and amylin have been linked to migraine. They are potent agonists of the AMY1 receptor, a heterodimer of the calcitonin receptor (CTR) and RAMP1. Co-expression of the CTR and CGRP has been reported in the TG, with little or no amylin observed. In the DRG, both peptides have been reported; however, their distribution relative to the CTR is unknown. This suggests that there may be differences in the relative abundance of each peptide between these two ganglia and which peptides might signal via CTR in each location. This study aimed to determine the relative distribution of the CTR with CGRP and amylin in the DRG and compare this to the TG.

Methods: In combination with neural markers, specific antibodies against CTR, CGRP and amylin were applied to mouse, rat, and human C1/2 DRG to investigate distribution. Data were compared to our prior TG data using the same conditions.

Results: In the DRG, CGRP-like immunoreactivity (LI) and amylin-LI were present in distinct and overlapping neurons, indicating occasional co-expression of the peptides. CTR-LI was present in neurons which expressed CGRP or amylin alone, as well as neurons which expressed both peptides. Co-staining was uncommon with an A-fibre marker, NF200, indicating that CTR-LI, CGRP-LI and amylin-LI were primarily in C-fibre neurons.

Conclusions: The expression of CGRP and CTR were similar between the DRG and TG. However, unlike the TG, abundant amylin expression and co-localisation with CTR was observed in the DRG. These data suggest that distinct local agonists may activate CTR-based receptors, such as the AMY1 receptor, in C-fibre neurons in the DRG and TG. This highlights that local amylin may play a more important role in DRG-mediated pain responses than in the TG.