Advancements in Understanding and Classifying Chronic Orofacial Pain: Key Insights from Biopsychosocial Models and International Classifications (ICHD-3, ICD-11, ICOP)

Canfora, Federica; Ottaviani, Giulia; Calabria, Elena; Pecoraro, Giuseppe; Leuci, Stefania; Coppola, Noemi; Sansone, Mattia; Rupel, Katia; Biasotto, Matteo; Di Lenarda, Roberto; Mignogna, Michele; Adamo, Daniela

doi:10.3390/biomedicines11123266

Cited by 1 publication

(2 citation statements)

References 142 publications

(180 reference statements)

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“…Preclinical research, including in vitro and in vivo studies, can provide invaluable data that are not feasible to investigate in humans [ 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 ]. This study showed that the incorporation of the C-3 side chain elicits subtle differences in curiosity and emotion in animal models of motor function.…”

Section: Discussionmentioning

confidence: 99%

“…This study showed that the incorporation of the C-3 side chain elicits subtle differences in curiosity and emotion in animal models of motor function. Ongoing clinical studies have advanced our understanding of the behavioral domains in neuropsychiatric conditions and have sought their potential management [ 184 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 ]. Furthermore, computational strategies accelerate our advancement in comprehending their pathology, as well as in developing novel strategies for the management of neurological and psychiatric disorders, including neurotropic computer-assisted drug design [ 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 ].…”

Section: Discussionmentioning

confidence: 99%

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The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

Martos,

Lőrinczi,

Szatmári

et al. 2024

IJMS

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The central nervous system (CNS) is the final frontier in drug delivery because of the blood–brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

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