Differential activation of ascending noxious pathways associated with trigeminal nerve injury

Okada, Shinji; Katagiri, Ayano; Saito, Hiroto; Lee, Jun; Ohara, Kinuyo; Iinuma, Toshimitsu; Bereiter, David A.; Iwata, Koichi

doi:10.1097/j.pain.0000000000001521

Cited by 25 publications

(23 citation statements)

References 77 publications

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“…VPM project to the somatosensory cortex and are involved in sensory discriminative aspects of pain, whereas medial thalamic nuclei project to the anterior cingulate cortex (ACC) and mediate affective aspects of pain (Iwata et al 2011). Since proportions of Vc neurons projecting to VPM and PBN are altered by trigeminal neuropathy (Okada et al 2019), it is possible that craniofacial muscle pain or TMD involves plasticity of ascending pain pathways. Neural pathways relevant to craniofacial muscle pain are depicted in Figure 3.…”

Section: Central Mechanisms For Craniofacial Muscle Painmentioning

confidence: 99%

Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments

et al. 2020

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Craniofacial muscle pain is highly prevalent in temporomandibular disorders but is difficult to treat. Enhanced understanding of neurobiology unique to craniofacial muscle pain should lead to the development of novel mechanism-based treatments. Herein, we review recent studies to summarize neural pathways of craniofacial muscle pain. Nociceptive afferents in craniofacial muscles are predominantly peptidergic afferents enriched with TRPV1. Signals from peripheral glutamate receptors converge onto TRPV1, leading to mechanical hyperalgesia. Further studies are needed to clarify whether hyperalgesic priming in nonpeptidergic afferents or repeated acid injections also affect craniofacial muscle pain. Within trigeminal ganglia, afferents innervating craniofacial muscles interact with surrounding satellite glia, which enhances the sensitivity of the inflamed neurons as well as nearby uninjured afferents, resulting in hyperalgesia and ectopic pain originating from adjacent orofacial tissues. Craniofacial muscle afferents project to a wide area within the trigeminal nucleus complex, and central sensitization of medullary dorsal horn neurons is a critical factor in muscle hyperalgesia related to ectopic pain and emotional stress. Second-order neurons project rostrally to pathways associated with affective pain, such as parabrachial nucleus and medial thalamic nucleus, as well as sensory-discriminative pain, such as ventral posteromedial thalamic nuclei. Abnormal endogenous pain modulation can also contribute to chronic muscle pain. Descending serotonergic circuits from the rostral ventromedial medulla facilitate activation of second-order neurons in the trigeminal nucleus complex, which leads to the maintenance of mechanical hyperalgesia of inflamed masseter muscle. Patients with temporomandibular disorders exhibit altered brain networks in widespread cortical and subcortical regions. Recent development of methods for neural circuit manipulation allows silencing of specific hyperactive neural circuits. Chemogenetic silencing of TRPV1-expressing afferents or rostral ventromedial medulla neurons attenuates hyperalgesia during masseter inflammation. It is likely, therefore, that further delineation of neural circuits mediating craniofacial muscle hyperalgesia potentially enhances treatment of chronic muscle pain conditions.

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Section: Central Mechanisms For Craniofacial Muscle Painmentioning

confidence: 99%

Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments

et al. 2020

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“…Sensory information that is integrated into a local, inter-neuronal circuit in the Vc is conveyed to the ventral posteromedial thalamic nucleus (VPM) and the parabrachial nucleus (PBN) by projection neurons [67]. The projection patterns are dependent on modality.…”

Section: Neuronal Circuits In the Trigeminal Sensory Nucleus Complexmentioning

confidence: 99%

“…In the case of a chronic constriction injury of the infraorbital nerve, C fiber-mediated responses are carried into both VPM and PBN. In contrast, mechanosensitive afferents preferentially terminate in the PBN, suggesting that Aδ fiber-mediated information is conveyed to the PBN [67]. Apart from the ascending pathway, direct monosynaptic input from TG neurons to the PBN is elucidated by genetic tools [68].…”

Section: Neuronal Circuits In the Trigeminal Sensory Nucleus Complexmentioning

confidence: 99%

Pathophysiological mechanisms of persistent orofacial pain

et al. 2020

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Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.

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“…Signals are transmitted centrally through these afferent fibers to the trigeminal spinal caudalis (Vc) nucleus of the brain stem where they synapse with second-order neurons that project to the somatosensory and limbic cortices via the thalamus (Figure 1). Throughout this ascending pathway, noxious information is modulated by both local and descending pain modulatory pathways that either inhibit or facilitate the transmitted sensory information [9,10]. Descending inputs to the Vc arise from the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), insula and from the Rostral Ventromedial Medulla (RVM) [8,11,12,13].…”

Section: Trigeminal Pain Pathwaysmentioning

confidence: 99%

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

Bista

Imlach

2019

Medicines

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Trigeminal neuropathic pain is a chronic pain condition caused by damage or inflammation of the trigeminal nerve or its branches, with both peripheral and central nervous system dysfunction contributing to the disorder. Trigeminal pain conditions present with diagnostic and therapeutic challenges to healthcare providers and often require multiple therapeutic approaches for pain reduction. This review will provide the overview of pathophysiology in peripheral and central nociceptive circuits that are involved in neuropathic pain conditions involving the trigeminal nerve and the current therapeutics that are used to treat these disorders. Recent advances in treatment of trigeminal pain, including novel therapeutics that target ion channels and receptors, gene therapy and monoclonal antibodies that have shown great promise in preclinical studies and clinical trials will also be described.

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Differential activation of ascending noxious pathways associated with trigeminal nerve injury

Cited by 25 publications

References 77 publications

Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments

Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments

Pathophysiological mechanisms of persistent orofacial pain

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

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