Laboratorij za istraživanje boli

LABORATORIJ ZA ISTRAŽIVANJE BOLI

Voditelj: prof. dr. sc. Damir Sapunar  [CV, pdf]

Članovi tima:
prof. dr. sc. Livia Puljak [CV, pdf]
Tihana Repić [CV]
Marica Maretić, viši laborant

Photo galerija

Ozljeda živčanih stanica i neuropatska bol

Ozljeda perifernog živca ključni je čimbenik u etiologiji neuropatske boli koju karakterizira osobita žestina i neosjetljivost na terapiju. Iako je poznato da je spinalni ganglij glavno mjesto početnih patofizioloških promjena u neuropatskoj boli, nisu poznati mehanizmi koji tu bol održavaju dugo nakon cijeljenja početne ozljede. Glavna tema naših istraživanja usmjerena je ka funkciji primarnih aferentnih neurona spinalnog ganglija koji prenose bolne podražaje. Ti neuroni pripadaju vrlo heterogenoj skupini s različitim osjetnim modalitetima, anatomskom distribucijom, receptorima, ekspresijom proteina, i što je najvažnije s različitom reakcijom na ozljedu. Među najvažnijim promjenama u ozlijeđenim primarnim aferentnim neuronima je pojačana podražljivost i ektopično generiranje podražaja. Nas zanima podskupina neurona spinalnog ganglija čije promjene u funkciji najznačajnije doprinose razvoju neuropatske boli. Naši rezultati (Sapunar et al. Anesthesiology 2005;103:360-376) ukazuju da presijecanje perifernog nastavka spinalnog živca dovodi do pojave stanica specifičnog fenotipa s elektrofiziološkim svojstvima koja odgovaraju i nociceptivnim neuronima i neuronima niskog praga podražljivosti. Kako bi dokazali naše hipoteze u istraživanjima koristimo nekoliko životinjski modela neuropatske boli, ciljanu dostavu tvari izravno u spinalni ganglij (J Neurosci Methods. 2009;177(2):397), testove ponašanja, histološke tehnike i elektrofiziološko snimanje s naknadnom imunofluorescencijskom identifikacijom snimanih stanica.

 
Tekući projekti:
HRZZ - Damir Sapunar - Treating neuropathic pain with dorsal root ganglion stimulation - NeuroMod 
Bilateralni hrvatsko-slovenski znanstveno istraživački projekt - Utjecaj periferne električne stimulacije na analgeziju

Dovršeni projekti
MZOS - Damir Sapunar - Nerve Injury and Neuropathic Pain (bibliografija)
MZOS - Damir Sapunar - Functional analysis of injured primary afferent neurons
HRZZ - Livia Puljak - NZZ - 02.05./28 - Molekularna memorija u dijabetičkoj neuropatiji (MEMODIN)
IASP - Livia Puljak - Initiative for Improving Pain Education Grant 
UKF 2A - Sandra Kostić - Neuropathic pain treatment: Gene transfer to nociceptive neurons
UKF 2A - Adriana Banožić - Facial expression as a pain indicator of socially excluded chronic pain patients
CREATE visiting scholar grant - Adriana Banožić - Influence of social exclusion on pain perception an emphaty in chronic pain patients
KAAD Stipend - Adriana Banožić - Effect of experimentally induced social exclusion on pain perception in elderly chronic pain patients

Suradnici
Prof.dr. Quinn Hogan, Laboratory for Pain research, MCW.
Prof.dr.sc. Violeta Ristou
dr.sc. Elsa Fabretti, Research Associate, University of Nova Gorica (Slovenia)

Izabrane publikacije

• 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. 
• Maxwell LJ, Wells GA, Simon LS, Conaghan PG, Grosskleg S, Scrivens K, Beaton DE, Bingham CO 3rd, Busse JW, Christensen R, Goel N, Jüni P, Kaiser U, Lyddiatt A, Mease PJ, Ostelo RW, Phillips K, Sapunar D, Singh JA, Strand V, Taylor AM, Terwee CB, Tugwell P. Current State of Reporting Pain Outcomes in Cochrane Reviews of Chronic Musculoskeletal Pain Conditions and Considerations for an OMERACT Research Agenda. J Rheumatol. 2015 Sep 15. pii: jrheum.141423.
• Banozic A, Grkovic I, Puljak L, Sapunar D. Behavioral changes following experimentally induced acute myocardial infarction in rats. Int. Heart J. 2014;55(2):169-77.
• Kostic S, Pan B, Guo Y, Yu H, Sapunar D, Kwok WM, Hudmon A, Wu HE, Hogan QH. Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons. Mol Cell Neurosci 2014;62:10-8.
• Chen Y, Chalmers I; TTi Editorial Alliance. Testing treatments interactive (TTi): helping to equip the public to promote better research for better health care. J Evid Based Med. 2015 May;8(2):98-102.
• Fidahić M, Dogan K, Sapunar D, Puljak L. National survey of pain clinics in Croatia: Organization and services. Acta Med Acad. 2015;44(1):18-30.
• Boric M, Skopljanac I, Ferhatovic L, Jelicic Kadic A, Banozic A, Puljak L. Reduced epidermal thickness, nerve degeneration and increased pain-related behavior in rats with diabetes type 1 and 2. Journal of Chemical Neuroanatomy. Accepted. 2013.
• Jelicic Kadic A, Boric M, Ferhatovic L, Banozic A, Sapunar D, Puljak L. Intrathecal inhibition of calcium/calmodulin-dependent protein kinase II in diabetic neuropathy adversely affects painrelated behavior. Neuroscience Letters. 2013. doi:pii: S0304-3940(13)00818-5. 
• 10.1016/j.neulet.2013.09.002.
• Boric M, Jelicic Kadic A, Ferhatovic L, Sapunar D, Puljak L. Calcium/calmodulin-dependent protein kinase II in dorsal horn neurons in long-term diabetes. NeuroReport. Accepted, 2013.
• Triva P, Jukic M, Puljak L. Access to public healthcare services and waiting times for patients with chronic nonmalignant pain: feedback from a tertiary pain clinic. Acta Clinica Croatica. 2013;52(1):79-85.
• Filipovic N, Ferhatovic L, Marelja I, Puljak L, Grkovic I. Increased vitamin D receptor expression in dorsal root ganglia neurons of diabetic rats. Neuroscience letters. 2013;549:140-145.
• Cosic A, Ferhatovic L, Banozic A, Kraljevic S, Maric A, Sapunar D, Puljak L. Pain catastrophizing changes during menstrual cycle. Psychology, Health & Medicine. 2013 Feb 26.
• Markotic F, Cerni Obrdalj E, Zalihic A, Pehar R, Hadziosmanovic Z, Pivic G, Durasovic S, Grgic V, Banozic A, Sapunar D, Puljak L. Adherence to pharmacological treatment of chronic nonmalignant pain in individuals aged 65 and older. Pain Medicine. 2013;14(2):247-56.
• Ferhatovic L, Banozic A, Kostic S, Sapunar D, Puljak L. Sex differences in pain-related behavior and expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2. Acta Histochemica. 2013;115(5):496-504.
• Ferhatovic L, Banozic A, Kostic S, Ticinovic Kurir T, Novak A, Vrdoljak L, Heffer M, Sapunar D, Puljak L. Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes. Anesthesia & Analgesia. 2013;116(3):712-21.
• Kostic S, Puljak L, Sapunar D. Attenuation of pain-related behaviour evoked by carrageenan injection through blockade of neuropeptide Y Y1 andY2 receptors. European Journal of Pain. 2013;17(4):493-504.
• Klinar I, Ferhatovic L, Banozic A, Raguz M, Kostic S, Sapunar D, Puljak L. Physicians' attitudes about interprofessional treatment of chronic pain: family physicians are considered the most important collaborators. Scandinavian Journal of Caring Sciences. 2013;27(2):303-10
• Jukic M, Kardum G, Sapunar D, Puljak L. Treatment of chronic musculoskeletal back pain in a tertiary pain clinic. Journal of Musculoskeletal Pain. 2012;4:277-283
• Busic Z, Kostic S, Kosta V, Carija R, Puljak L, Sapunar D. Postlaminectomy stabilization of the spine in a rat model of neuropathic pain reduces pain-related behavior. Spine 2012;37(22):1874-82.
• Sapunar D, Banozic A, Kostic S, Puljak L. Dorsal root ganglion - a potential new therapeutic target for neuropathic pain. J Pain Res. 2012;5:31-8.
• Kraljevic S, Banozic A, Maric A, Cosic A, Sapunar D, Puljak L. Parents' pain catastrophizing is related to pain catastrophizing of their adult children. Int J Behav Med. 2012 Mar;19(1):115-9.
• Fischer G, Kostic S, Nakai H, Park F, Sapunar D, Yu H, Hogan Q. Direct injection into the dorsal root ganglion: Technical, behavioral, and histological observations. J Neurosci Methods. 2011 Jul 15;199(1):43-55
• Puljak L, Sapunar D. Web-Based Elective Courses for Medical Students: An Example in Pain. Pain Med. 2011 Jun;12(6):854-63
• Sapunar D, Vukojević K, Kostić S, Puljak L. Attenuation of pain-related behavior evoked by injury through blockade of neuropeptide Y Y2 receptor. Pain 2011 May;152(5):1173-81.
• Lovric Kojundzic S, Puljak L, Hogan Q, Sapunar D. Depression of Ca/calmodulin-dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation. J Comp Neurol 2010 Jan 1;518(1):64-74.
• Puljak L, Lovric Kojundzic S, Hogan Q, Sapunar D. Lidocaine injection into the rat dorsal root ganglion causes neuroinflammation and pain-related behavior. Anesth Analg.2009 Mar 108;(3):1021-6.
• Kosta V, Lovric Kojundzic S, Cambj Sapunar L, Sapunar D. Spine deformity in a rat model of neuropathic pain causes pain-related behavior. Eur J Pain. 2009 Mar:13(3):243-8.
• Puljak L, Lovric Kojundzic S, Hogan QH, Sapunar D. Targeted delivery of pharmacological agents into rat dorsal root ganglion. J Neurosci Methods. 2009 Mar 15;177(2):397-402.
• Hogan Q, Lirk P, Poroli M, Rigaud M, Fuchs A, Fillip P, Ljubkovic M, Sapunar D. Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons. Anesth Analg. 2008 Sep;107(3):1045-51.
• Znaor L, Lovric S, Hogan Q, Sapunar, D. Association of neural inflammation with hyperalgesia following spinal nerve ligation, Croat Med J, 48 (2007) 35-42.
• Sapunar D, Ljubković M, Lirk P, McCallum JB, Hogan QH. Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons. Anesthesiology 2005;103:360-76.
• Sapunar D, Modric-Jednacak K, Grkovic I, Michalkiewicz M, Hogan Q. Effect of peripheral axotomy on pain-related behavior and dorsal root ganglion neurons excitability in NPY transgenic rats. Brain Res 2005;1063(1):48-58.

 

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