title: Involvement of aberrant calcium signalling in herpetic neuralgia.
abstract: Alpha-herpesviruses, herpes simplex viruses (HSV) and varicella zoster virus (VZV), are pathogens of the peripheral nervous system. After primary infection, these viruses establish latency within sensory ganglia, while retaining the ability to reactivate. Reactivation of VZV results in herpes zoster, a condition characterized by skin lesions that leads to post-herpetic neuralgia. Recurrent reactivations of HSV, which cause mucocutaneous lesions, may also result in neuralgia. During reactivation of alpha-herpesviruses, satellite glial cells (SGCs), which surround neurons in sensory ganglia, become infected with the replicating virus. SGCs are known to contribute to neuropathic pain in a variety of animal pain models. Here we investigated how infection of short-term cultures of mouse trigeminal ganglia with HSV-1 affects communication between SGCs and neurons, and how this altered communication may increase neuronal excitability, thus contributing to herpetic neuralgia. Mechanical stimulation of single neurons or SGCs resulted in intercellular calcium waves, which were larger in cultures infected with HSV-1. Two differences were observed between control and HSV-1 infected cultures that could account for this augmentation. Firstly, HSV-1 infection induced cell fusion among SGCs and neurons, which would facilitate the spread of calcium signals over farther distances. Secondly, using calcium imaging and intracellular electrical recordings, we found that neurons in the HSV-1 infected cultures exhibited augmented influx of calcium upon depolarization. These virally induced changes may not only cause more neurons in the sensory ganglia to fire action potentials, but may also increase neurotransmitter release at the presynaptic terminals in the spinal cord. They are therefore likely to be contributing factors to herpetic neuralgia.
authors.affiliation: Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel. Electronic address: rawarwick87@gmail.com.
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Warwick
authors.affiliation: Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Hanani
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002229:Carbenoxolone / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000821:virology; D018139:Simplexvirus / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology; D014775:Virus Activation / Q000187:drug effects
chemical_list: D049452:Green Fluorescent Proteins; D003035:Cobalt; D000255:Adenosine Triphosphate; C018021:cobaltous chloride; D002229:Carbenoxolone; D002118:Calcium
keywords: Alpha-herpesviruses; Herpetic neuralgia; Intercellular calcium signalling; Satellite glial cells; Sensory ganglia