Multi-dimensional role of the parabrachial nucleus in regulating pain-related affective disturbances in trigeminal neuropathic pain

Abstract

Neuropathic pain is characterized by sensory abnormalities, such as mechanical allodynia and heat hyperalgesia, associated with alteration in the peripheral and central nervous systems. After trigeminal nerve injury, phenotypic changes that involve the expression of calcitonin generelated peptide occur in large-and medium-sized myelinated neurons; primary afferent neurons exhibit hyperexcitability because of neuron-glia interactions in the trigeminal ganglion. Increased nociceptive inputs from C-and Aδ-fiber and innocuous inputs from Aβ-fiber into the trigeminal spinal subnucleus caudalis (Vc) contribute to the phenotypic changes; further, they potentiate noxious information transmission in the ascending nociceptive pathways to the thalamus and parabrachial nucleus (PBN). It is noteworthy that C-fiber mediated nociceptive inputs can activate both the Vc-ventral posteromedial thalamic nucleus and Vc-PBN pathways, while mechanoreceptive fiber inputs specifically activate the Vc-PBN pathway. The Vc-PBN pathways project to the central nucleus of the amygdala (CeA) where affective behaviors are modulated. In addition, the PBN interacts with wakefulness-regulating neurons and hunger-sensitive neurons in the hypothalamus, suggesting that the Vc-PBN pathway can modulate sleep and appetite. Therefore, phenotypic changes in primary neurons and stimulus modality-specific activation of ascending nociceptive pathways to the PBN may exacerbate affective aspects of trigeminal neuropathic pain, including behavioral problems, such as sleep disturbance and anorexia, via the PBN-CeA-hypothalamus circuits.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice

“…In pain regulation, the PBN mainly projects to the CeA, BNST, PAG, intralaminar thalamic nucleus (ILN), ventral tegmental area (VTA), etc. [14,17,34,36]. Deng et al [14] showed that PBN directly transmits injurious signals from the spinal cord to the intralaminar thalamic nuclei.…”

Persistent, neuropathic-like trigeminal pain after dental implant loading

“…They can be functionally reconfigured in pathological states such as nerve lesions, through activation/inhibition of interneurons and glial cells, with specificities according to the nature of the injury ( 28 , 29 ). Changes in the spinal/trigeminal system, involving for example GABA and PKCγ interneurons and glial cells ( 30 - 35 ), have been documented. This changes can explain why a mechanical sensation can lead to persistent pain ( 36 ).…”

Maintaining Tooth Vitality With Super Minimally Invasive Pulp Therapy

“…Porporatti et al reported that patients with pulpitis experienced neuropathic pain and somatosensory alterations not only before treatment but also after pulpectomy [ 16 ]. Various theories regarding the cause of this phenomenon have been proposed, and importantly, a relationship between the parabrachial nucleus and trigeminal nerve has recently been reported [ 17 ]. Nociceptive information in the trigeminal nerve area is synaptically mediated in the parabrachial nucleus and is then projected to the limbic nuclei involved in pain and emotions.…”

“…Nociceptive information in the trigeminal nerve area is synaptically mediated in the parabrachial nucleus and is then projected to the limbic nuclei involved in pain and emotions. Thus, pain in the trigeminal nerve-innervated area and facial pain might be easily influenced by emotions [ 17 ]. Residual pain after pulpectomy and prolonged pain can increase patients' anxiety and fear and induce chronic orofacial pain.…”