Role of enkephalins in neurophatic pain

Mehanizmi nastanka i održavanja kronične neuropatske boli izuzetno su kompleksni te, između ostalog, uključuje brojne periferne i središnje promjene broja i funkcije različitih molekula, poput N tipa Ca2+ kanala, TRPV1 vaniloidnih receptora, Na+ kanala, kao i opioidnih mi, delta i kapa receptora.Brojna istraživanja su pokazala značajnu ulogu endogenog opioidnog sustava u procesima transmisije i modulacije bolne informacije. Od tri glavne skupine opioidnih peptida, najviše dokaza o uključenosti u nociceptivne procese na spinalnoj razini dostupno je za enkefaline. Iako je primarno inhibitornog djelovanja, uloga opioidnog sustava kod kroničnih boli može biti značajno promijenjena. Upravo je uloga opioidnog sustava kod neuropatskih boli kompleksne patofiziologije i kroničnog trajanja najčešće istraživana, a dobiveni rezultati fundamentalnih istraživanja ponekad daju kontradiktorne rezultate. U ovom diplomskom radu mjerena je imunoreaktivnost enkefalina imunohistokemijskom metodom u uzorcima tkiva dorzalnog roga kralježnične moždine kontrolnih životinja i životinja s neuropatskom boli uzrokovanom parcijalnom transekcijom perifernog živca. Pokazali smo da se nakon jednostrane ozljede živca imunoreaktivnost enkefalina u dorzalnom rogu povećava obostrano. To nas dovodi do zaključka da usprkos povećanoj koncentraciji enkefalina, u stanjima kronične hiperosjetljivosti dolazi do smanjenja broja μ, a vjerojatno i δ opioidnih receptora preko kojih enkefalini ostvaruju svoje fiziološke učinke. Kako bi se skupili dodatni dokazi o navedenoj hipotezi, potrebna su daljnja istraživanja koja će doprinijeti boljem razumijevanju kompleksnog fenomena neuropatke boli, te u konačnici rezultirati učinkovitijim liječenjem oboljelih.Mechanism of development and maintenance of chronic neuropathic pain is extremely complex and, among other things, includes a number of peripheral and central changes in the number and function of various molecules such as N type Ca2+ channel, TRPV1 vanilloid receptor, tetrodotoxin (TTX)-sensitive Na+ channels and the ASIC ionic channels, as well as opioid mu, delta and kappa receptors. Numerous research has shown the significant role the endogenous opioid system has in processes of transmission and modulation of painful stimuli. Of the three main opioid peptide groups, the best evidence for their involvement in the regulation of nociceptive processes on the spinal level has been found for enkephalins. Albeit primarily inhibitory, the role of the opioid system in chronic pain can be substantially altered. It is precisely the role that the opioid system has in neuropathic pain of complex pathophysiology and chronic in its character that is primarily the subject of research, and the results of fundamental research sometimes show contradictory conclusions. In this work enkephalin immunoreactivity was measured by immunohistochemical methods in tissue samples of the dorsal horn of the spinal cord of control animals and animals with neuropathic pain induced by partial transection of a peripheral nerve. We have shown that after a unilateral nerve injury enkephalin immunoreactivity in the dorsal horn enhances on both sides. This brings us to the conclusion that despite the increased enkephalin concentration, in conditions of chronic hypersensitivity decreases the number of μ and probably δ opioid receptors through which enkephalins exercise their physiological effects. In order to gather further evidence on the above hypothesis, further research is needed that will contribute to a better understanding of the complex phenomenon neuropathic pain, and ultimately result in more effective treatment of patients