Abstract Olfaction, despite being evolutionarily one of the oldest senses, is complex in structure and function. It can distinguish between trillions of odorants, provides orientation, mediates social interactions, and serves as a warning system. Sensory signals from the periphery are first processed in the olfactory bulb (OB) and then distributed to several olfactory cortical structures. Unlike other sensory modalities, this primary sensory information is not relayed via the thalamus. One prominent olfactory cortical region is the anterior olfactory nucleus (AON), a two-layered structure located within the olfactory peduncle. The AON exerts strong reciprocal connections not only to the OB but also to higher brain areas, e.g., the piriform cortex (PCx), thereby serving as a hub for bottom-up and top-down information processing. However, the functional role of the AON is not well-understood. Here, we provide an overview of recent publications investigating the function of AON in olfactory processing and behavior and present a framework for future research on this fascinating archicortical structure.
Abstract The olfactory epithelium (OE) and its associated perireceptor space, i.e., the mucus layer (ML) covering the epithelium, are the most peripheral parts of the vertebrate olfactory system. The olfactory receptor neurons (ORNs), one of the cell types of the OE, are the odorant detectors of the olfactory system. These bipolar neurons extend their apical appendages, which express odorant receptors, into the ML. The binding of odorants to odorant receptors is the initial step of odor processing. The vast majority of research on the peripheral olfactory system has focused on the ORNs and the molecular components of the olfactory transduction cascades. Less attention has been directed to the other cell types of the OE and their physiological functions. For a long time, it was assumed that the olfactory signals detected in the OE are transmitted to the olfactory bulb without preprocessing, but this view turned out to be over-simplistic. It has been shown that the olfactory signals are critically modulated already in the OE. Despite compelling evidence, many descriptions of the olfactory system still ignore the existence of these peripheral modulatory mechanisms. The importance of peripheral modulation of the olfactory signals, the physiological functions of the other epithelial cell types, the extrinsic innervation of the olfactory mucosa, and the perireceptor space are only slowly coming into focus in the olfactory research. Furthermore, several intraepithelial signaling pathways that signal epithelial damage and initiate regenerative processes have recently been discovered. This review provides a concise overview of the current knowledge of peripheral events in the olfactory mucosa and the perireceptor space.
Abstract Brain circuits involved in pain chronicity shift from areas involved in nociceptive processing to those associated with emotional and motivational processes. They overlap with circuits relevant for anxiety, fear and depression and are characterized by deficient prefrontal control mechanisms. Noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation, transcranial direct and alternating current stimulation directly impact on these circuits and pain. Neurofeedback and brain-computer interfaces as well as various types of cognitive and behavioral interventions also alter these circuits. The analysis of brain changes related to pain chronicity helps to mechanistically tailor interventions to patient characteristics, can increase treatment efficacy and efficiency and can identify new treatment approaches.
Abstract Several forms of chronic pain do not respond to the conventional analgesics, such as opioids, but can be treated with antidepressants, such as serotonin and noradrenalin reuptake inhibitors (SNRIs). Recent studies indicate that noradrenalin signalling is a key target for SNRI-induced analgesia in neuropathic pain. SNRIs inhibit chronic pain by blocking reuptake of noradrenalin and subsequent activation of adrenergic receptors on neurons in the dorsal horn of the spinal cord. However, in the nervous system, various subtypes of adrenergic receptors are highly expressed by astrocytes and microglial cells. Activation of these receptors on astrocytes engages complex intracellular signalling pathways and prevents inflammatory changes of microglia, which in turn can affect neuronal activity. Hence, SNRIs-induced modulations of the glial cell physiology can impact neural circuit functions and pain perception. In this review, we summarize our current knowledge on the impact of SNRIs on glial cells and in modulating chronic pain in experimental animal models.
Abstract Interactions of the immune system and the nociceptive system play an important role in the generation and maintenance of pain in musculoskeletal diseases and in disease development. In inflamed tissue peripheral nociceptive neurons are rendered hyperexcitable by proinflammatory cytokines, antigen/antibody complexes and other immune mediators. Spinal nociceptive neurons are rendered hyperexcitable with the support of microglial cells, the immune cells of the central nervous system. The so-elicited sensitization of pain pathways has a strong impact on pain processing in the brain. On the other hand, immune processes are regulated by the nervous system. Sensory neurons, by releasing neuropeptides, and efferent neurons of the sympathetic nervous system support immune processes which promote disease development.
