Projections from the insular cortex to pain-receptive trigeminal caudal subnucleus (medullary dorsal horn) and other lower brainstem areas in rats

This study examined the projections from the rat insular cortex (Ins) to lower brainstem areas which are possibly involved in orofacial pain processing. We first examined distributions of Ins neurons projecting directly to the trigeminal caudal subnucleus (Vc, medullary dorsal horn) and oral subnucleus (Vo) which are known to receive orofacial nociceptive inputs. After injections of a retrograde tracer, Fluorogold (FG), into the medial part and lateral part of laminae I/II of Vc, many neurons were labeled bilaterally with a contralateral predominance in the rostral level of granular Ins (GI) and dysgranular Ins (DI) and the caudal level of GI/DI, respectively, but none in the agranular Ins (AI). After FG injections into laminae III–V of Vc, no Ins neurons were labeled. After FG injections into the Vo, many neurons were labeled bilaterally with a contralateral predominance in the rostral and caudal GI/DI, but none in the AI. We then examined descending projections from the GI/DI to the lower brainstem. After injections of an anterograde tracer, biotinylated dextranamine (BDA), into the rostral GI/DI, many BDA-labeled axons and terminals were seen bilaterally with a contralateral predominance in the medial part of laminae I/II of Vc, dorsomedial Vo, juxtatrigeminal region, rostral ventromedial medulla (RVM), and nucleus of the solitary tract, and with an ipsilateral predominance in the parabrachial nucleus (Pb), Kölliker–Fuse nucleus (KF) and trigeminal mesencephalic nucleus. After BDA injections into the caudal GI/DI, they were seen bilaterally with a contralateral predominance in the lateral part of laminae I/II of Vc, ventrolateral Vo, juxtatrigeminal region and RVM, and with an ipsilateral dominance in the lateral zone (PAGl) of periaqueductal gray, Pb and KF. These results suggest that orofacial nociceptive processing of Vc and Vo neurons may be regulated by GI/DI directly or indirectly through brainstem nuclei such as PAGl, Pb, KF and RVM.

► Granular and dysgranular insula project to select trigeminal (V) subnuclei.
► They topographically project to laminae I/II of V caudalis and to V oralis.
► They do not project to laminae III–V of V caudalis.
► Agranular insula does not project to these V subnuclei.
► Granular and dysgranular insula also project to other pain-related brainstem areas.