Title Učinci neurostimulacije spinalnog ganglija u životinjskim modelima i u liječenju boli u ljudi Title (english) Efficacy and safety of dorsal root ganglion stimulation for tretment of different pain conditions in humans and in animal pain models Author Ivana Vuka Mentor Livia Puljak (mentor)Committee member Maja Valić (predsjednik povjerenstva)Committee member Ozren Polašek (član povjerenstva)Committee member Srećko Gajović (član povjerenstva)Granter University of Split Defense date and country 2021, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 61 - Medical sciences Abstract Cilj:
Na sustavan način prikupiti dokaze i sintezom dokaza analizirati učinkovitost neurostimulacije na parametre i ishode povezane s boli u životinjskim modelima boli te učinkovitost i sigurnost primjene električne stimulacije i pulsne radiofrekvencije za liječenje različitih bolnih stanja u ljudi. Temeljem rezultata dobivenih provedbom sustavnih pregleda razviti neurostimulator i metodologiju koja se može korsititi u translacijskim istraživanjima posebno otkrivanju mehanizma neuromodulacije i testiranja novih modaliteta liječenja.
Metode:
Za svaki od sustavnih pregleda pretražene su najmanje tri bibliografske baze podataka, a za sustavni pregled o intervenciji u ljudi dodatno i registri kliničkih istraživanja. Kvalitea uključenih istraživanja analizirana je korištenjem Cochraneovog alata za procjenu rizika pristranosti za randomizirana kontrolirana istraživanja i ROBINS-I alata za rizik pristranosti u nerandomiziranim istraživanjima. U eksperimentalnom istraživanju posebno dizajniran Neuromod stimulator korišten je za implantraciju u Sprague-Dawley (SD) štakorie težine 300-400 g. Ukupno je korišteno 45 životinja raspoređenih u jednu od skupina: skupina s podvezanim spinalnim živcem (SNL) (N=6), skupina s kroničnom kompresijskom ozljedom spinalnog ganglija (CCD) (N=9), SNL skupina s ugrađenim stimulatorom (N=11), netaknuta kontrolna skupina (N=6), skupina s ugrađenim lažnim stimulatorom (N=8) i lažnom elektrodom (N=7).
Rezultati:
U tri provedena sustavna pregleda o učinkovitosti i sigurnosti neurostimulacije u ljudi ukupno su ukjučena 74 istraživanja. Iako su imala generalno pozitivne zaključke o učinku neurostimulacije za različita bolna stanja, istraživanja su bila loše kvalitete s malim brojem uključenih ispitanika dok meta-analiza nije bila moguća zbog velike heterogenosti. U sustavni pregled na životinjskim modelima uključeno je 14 istraživanja koja su također pokazala pozitivan učinak neurostimulacije na koncentracije parametara i ponašanje povezano s boli, ali su bili loše metodološke kvalitete. U eksperimentalnom istraživanju razvijen je funkcionalni stimulator za korištenje u životinjskim modelima boli čija je funkcionalnost potvrđena u zdravih i ozlijeđenih životinja. U životinja sa izazvanom ozljedom spinalnog živca pokazano je da neurostimulacija utječe na smanjenje ponašanja povezanog s boli, dok postavljena elektroda ne uzrokuje kompresiju spinalnog ganglija.
Zaključak:
Do sada objavljena istraživanja pokazuju da neurostimulacija spinalnog ganglija može pomoći pacijentima koji nisu postigli odgovarajuće smanjenje boli drugim farmakološkim i nefarmakološkim metodama. Dostupni dokazi o učinkovitosti i sigurnosti električne i PRF stimulacije za liječenje kronične boli trebaju se smatrati preliminarnim i potrebno ih je potvrditi provođenjem visokokvalitetnih randomiziranih kontroliranih ispitivanja s dovoljnim brojem sudionika. Eksperimentalno razvijeni stimulator omogućava širok spektar istraživačkih primjena od prilagođavanja parametara stimulacije različitim uvjetima boli, proučavanja novih načina stimulacije poput visokofrekventne stimulacije do dobivanja odgovora o analgetskim mehanizmima stimulacije spinalnog ganglija.
Abstract (english) Objectives:
Collect evidence about effecacy of neurostimulation in a systematic way for the parameters and outcomes associated with pain in animal models of pain and the effeicacy and safety of electrical stimulation and pulsed radiofrequency for the treatment of various painful conditions in humans. Based on the results obtained by conducting systematic reviews, develop a neurostimulator and a methodology that can be used in translational research, especially for the discovery of the mechanism of neuromodulation and testing of new treatment modalities.
Methods:
At least three bibliographic databases were searched for each of the systematic reviews, and clinical trials registers were additionally searched for the systematic reviews of the intervention in humans. The quality of the included studies was analyzed using the Cochrane risk of bias tool for randomized controlled trials and the ROBINS-I risk of bias tool in nonrandomized trials. In the experimental study, a specially designed Neuromod stimulator was used for implantation in Sprague-Dawley (SD) rats weighing 300-400 g. A total of 45 animals were used divided into one of the groups: the group with spinal nerve ligation (SNL) (N=6), the group with chronic compression injury (CCD) (N=9), the SNL group with implanted stimulator (N=11), intact control group (N=6), group with implanted false stimulator (N=8) and false electrode (N=7).
Results:
A total of 74 studies were included in three systematic reviews of the efficacy and safety of neurostimulation in humans. Although they had generally positive conclusions about the effect of neurostimulation for different painful conditions, the studies were of poor quality with a small number of participants involved while meta-analysis was not possible due to high heterogeneity. A systematic review in animal models included 14 studies that also showed a positive effect of neurostimulation on pain-related parameters and pain-related behavior, but were of poor methodological quality. In an experimental study, a functional stimulator was developed for use in animal models of pain whose functionality was confirmed in healthy and injured animals. In animals with spinal nerve ligation, neurostimulation has been shown to reduce pain-related behavior, while the electrode does not cause dorsal root ganglion compression.
Conclusion:
Research published so far shows that neurostimulation of the spinal ganglion can help patients who have not achieved adequate pain reduction by other pharmacological and nonpharmacological methods. Available evidence on the efficacy and safety of electrical and PRF stimulation for the treatment of chronic pain should be considered preliminary and should be confirmed by conducting high-quality randomized controlled trials with a sufficient number of participants. The experimentally developed stimulator enables a wide range of research applications from adjusting stimulation parameters to different pain conditions, studying new stimulation methods such as high-frequency stimulation to obtaining answers about analgesic mechanisms of dorsal root ganglion stimulation.
Keywords
kronična bol
ljudi
električna stimulacija
spinalni gangliji
modeli životinjskih bolesti
sustavni pregledi kao tema
Keywords (english)
Chronic Pain
Humans
Electric Stimulation
Spinal Ganglia
Animal Disease Models
Systematic Reviews as Topic
Language croatian URN:NBN urn:nbn:hr:171:081533 Study programme Title: Translational Research in Biomedicine - TRIBE Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-05-03 11:55:08
