Abstract
Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious stimulation. We previously have shown most efferent projections from this locus project to areas implicated either in the processing or modulation of pain. Here we show the cmVLM of the rat receives projections from superficial laminae of the medullary dorsal horn (MDH) and has neurons activated with capsaicin injections into the temporalis muscle. Injections of either biotinylated dextran amine (BDA) into the MDH or fluorogold (FG)/fluorescent microbeads into the cmVLM showed projections from lamina I and II of the MDH to the cmVLM. Morphometric analysis showed the retrogradely-labeled neurons were small (area 88.7 µm2±3.4) and mostly fusiform in shape. Injections (20–50 µl) of 0.5% capsaicin into the temporalis muscle and subsequent immunohistochemistry for c-Fos showed nuclei labeled in the dorsomedial trigeminocervical complex (TCC), the cmVLM, the lateral medulla, and the internal lateral subnucleus of the parabrachial complex (PBil). Additional labeling with c-Fos was seen in the subnucleus interpolaris of the spinal trigeminal nucleus, the rostral ventrolateral medulla, the superior salivatory nucleus, the rostral ventromedial medulla, and the A1, A5, A7 and subcoeruleus catecholamine areas. Injections of FG into the PBil produced robust label in the lateral medulla and cmVLM while injections of BDA into the lateral medulla showed projections to the PBil. Immunohistochemical experiments to antibodies against substance P, the substance P receptor (NK1), calcitonin gene regulating peptide, leucine enkephalin, VRL1 (TPRV2) receptors and neuropeptide Y showed that these peptides/receptors densely stained the cmVLM. We suggest the MDH- cmVLM projection is important for pain from head and neck areas. We offer a potential new pathway for regulating deep pain via the neurons of the TCC, the cmVLM, the lateral medulla, and the PBil and propose these areas compose a trigeminoreticular pathway, possibly the trigeminal homologue of the spinoreticulothalamic pathway.
Highlights
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage [1]
It should be noted that retrogradely labeled neurons often were noted in superficial laminae of the medullary dorsal horn (MDH) after biotinylated dextran amine (BDA) injections centered in the caudal pressor area (CPA)
Injections of capsaicin into the temporalis muscle of rats induced c-Fos labeling in the dorsomedial part of the trigeminocervical complex (TCC), the caudalmost ventrolateral medulla (cmVLM), the lateral reticular formation (LRF), and the parabrachial complex (PBil). We propose these areas are directly connected and form a pathway from the TCC through the cmVLM-LRF-PBil (Fig. 9) to the medial thalamus, and are important for mediating deep pain from head and neck regions
Summary
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage [1]. The spinothalamic pathway conveys the conscious perception of pain and has been studied extensively. This pathway carries nociceptive impulses generated peripherally in Ad and C fibers that project mainly to neurons in laminae I, II, and V of the dorsal horns. The spinoreticulothalamic pathway, called the paleospinothalamic tract because of its origin in early evolution, mediates arousal as well as the autonomic and emotional aspects of pain. It is assumed that noxious information conveyed over the spinoreticulothalamic pathway uses similar sensory fibers into the dorsal horn, is relayed to neurons in deeper lamina of the spinal cord, and ascends to the medulla and pons before projecting to the medial nuclear group of the thalamus [2,4]
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