Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2938
• Main Authors: Aczél, Timea, Kecskés, Angéla, Kun, József, Szenthe, Kálmán, Bánáti, Ferenc, Szathmary, Susan, Herczeg, Róbert, Urbán, Péter, Gyenesei, Attila, Gaszner, Balázs, Helyes, Zsuzsanna, Bölcskei, Kata
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.04.2020; MDPI
• Subjects: Analgesics; Animals; Binding sites; Biomarkers; Calcitonin; Calcitonin gene-related peptide; complete Freund’s adjuvant; Cytotoxicity; Disease Models, Animal; Disease Susceptibility; Face recognition; Facial Pain - etiology; Facial Pain - metabolism; Facial Pain - physiopathology; Fluorescent Antibody Technique; Ganglia; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene regulation; Genes; Glial cells; Headache; hemokinin-1; Hybridization; Hyperalgesia; Inflammation; macrophages; Macrophages - metabolism; Mice; Mice, Knockout; Microglia; Migraine; Neuroglia - metabolism; Neuronal-glial interactions; Neurons; Neuropeptides; Nuclei (cytology); orofacial pain; Pain; Pain perception; Peptides; RNA polymerase; satellite glial cells; Sensory neurons; Sensory Receptor Cells - metabolism; Tachykinin; Tachykinin receptors; Tachykinins - genetics; Tachykinins - metabolism; trigeminal ganglia; Trigeminal ganglion; Trigeminal Ganglion - metabolism; Trigeminal nerve; Trigeminal Neuralgia - etiology; Trigeminal Neuralgia - metabolism; orofacial pain; trigeminal ganglia; macrophages; hemokinin-1; neuroinflammation; complete Freund’s adjuvant; satellite glial cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082938

A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund's adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that expression increased in the TG in response to inflammation. Duration-dependent upregulation was associated with the extent of the facial allodynia. was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and -deficient ( ) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.