Project title: Treating neuropathic pain with dorsal root ganglion stimulation - NeurMod
Principal Investigator: Damir Sapunar
Duration of the project: 4 years
Begining of the project: December 15th 2014.
Granting agency: Hrvatska zaklada za znanost (HRZZ)
Doktorandi: Tihana Repić
; Ivana Vuka
Neuropathic pain is a debilitating disease of the somatosensory system that has a huge socio-economic impact. Numerous studies, including those from our laboratory have established that the injured dorsal root ganglion (DRG) is the important site for pathophysiologic changes that lead to development of neuropathic pain. Although DRG neurons are critical for the onset of neuropathic pain, there are no relevant clinical treatments for neuropathic pain that target this organ. With this proposal we aim to prove that neurostimulation techniques can be successfully used to manipulate neuronal function at the level of experimentally injured DRGs. In order to test this hypothesis we will construct a fully implantable neuronal stimulator for freely moving rats, devise an implantation technique and define stimulation protocols. This stimulator will be tested in rats with two types of experimentally induced nerve injury; spinal nerve ligation and carrageenan-induced inflammation model. Since this invasive procedure bears substantial risk of inflammation and other adverse neural tissue response, which can induce pain per se,
we will also investigate connective tissue fibrosis and neuroinflammatory response in neural tissue of DRG and dorsal horn. The effect of the stimulation on excitability of injured DRG neurons will also be tested in vitro
. Our last aim builds on our previous study in which we showed that neuronal injury may disable T-junction filtering and thereby increase the net conduction of afferent traffic. With this proposal we will test whether stimulation can modulate filtering properties of DRG T-junction. This will be addressed using recordings from injured sensory neurons of dorsal root ganglia excised from adult rats, and recently developed methodology that will allow us to electrically visualize action potential propagation in DRG neurons grown over custom microelectrode arrays.
Repić T, Madirazza K, Bektur E, Sapunar D. Characterization of dorsal root ganglion neurons cultured on silicon micro-pillar substrates. Sci Rep 2016;23(6):39560
Vuka, I, Vučić K, Repic K, Ferhatovic Hamzić L, Sapunar D, Puljak L. Electrical Stimulation of Dorsal Root Ganglion in the Context of Pain: A Systematic Review of In Vitro and In Vivo Animal Model Studies. Neuromodulation 2017 Nov 20. doi: 10.1111/ner.12722
Vuka I., Vucic K, Repic T, Ferhatovic Hamzic L, Sapunar D, Puljak L. Electrical stimulation of dorsal root ganglia (DRG) in animal models: a systematic review. In: European Pain School, 2017 June 4 - 10, Siena, Italy.
Vuka I., Vucic K, Repic T, Ferhatovic Hamzic L, Sapunar D, Puljak L. Electrical stimulation of dorsal root ganglion – a new therapeutic approach for neuropathic pain. In: 21st Young Neuroscientist Meeting, 2017 June 29th, Zagreb, Croatia.
Vuka I, Vucic K, Repic T, Ferhatovic Hamzic L, Sapunar D, Puljak L. Electrical stimulation of dorsal root ganglion in the context of pain: a systematic review of in vitro and in vivo animal model studies. In: 6th Croatian Neuroscience Congress, 2017 September 16 – 18, Osijek, Croatia.
Vuka I, Repic T. Vucic K, Dosenovic S., Ferhatovic Hamzic L, Sapunar D, Puljak L. Electrical stimulation of dorsal root ganglion in the context of pain: systematic reviews of animal and human studies. In: COST EMF-MED Workshops and WG Meetings, 2017 October 26 – 27, Vienna, Austria.