About

Olga Korczeniewska is an Associate Professor in the Department of Diagnostic Sciences at Rutgers School of Dental Medicine. Her research interests include investigating molecular mechanisms contributing to neuropathic pain development and maintenance, as well as sex-dimorphism of pain. She collaborates with a team of researchers to explore the predictive value of exercise-induced hypoalgesia profiles in rats on pain intensity inflicted by peripheral nerve injury. Her work involves using animal models of neuropathic pain to identify gene expression changes associated with pain development and maintenance in both male and female rats, with the long-term goal of identifying molecular targets for mechanism-based and more effective treatments for neuropathic pain. Her educational background includes a BA in Computer Science from Rutgers University/New Jersey Institute of Technology and a PhD in Biomedical Sciences from Rutgers University.

Research topics

• Neuroscience
• Medicine
• Anesthesia
• Pathology
• Psychology
• Physical therapy
• Biology
• Surgery
• Genetics
• Anatomy
• Dentistry
• Internal medicine
• Endocrinology

Selected publications

• Pharmacogenetic associations of CYP2D6 and CYP2C19 variants with anticholinergic drug burden and hyposalivation

  Frontiers in Pharmacology · 2025-11-19

  articleOpen access1st author

  Introduction Anticholinergic medications frequently cause hyposalivation (decreased saliva flow) through parasympathetic inhibition. This adverse effect is related to anticholinergic burden, reflecting the cumulative exposure to drugs with anticholinergic properties. Genetic variation in CYP genes, which encode drug-metabolizing enzymes, alters drug metabolism, potentially influencing systemic anticholinergic burden. This study investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes are associated with anticholinergic burden and hyposalivation. Methods Adults taking at least one CYP substrate anticholinergic medication reporting xerostomia (oral dryness) were recruited. Anticholinergic burden was quantified using the Anticholinergic Drug Scale (ADS) and Serum Anticholinergic Activity (SAA). Salivary assessment included unstimulated whole saliva (UWS) and minor saliva flow (MSF). Participants were genotyped for functional variants of CYP2D6 and CYP2C19 . Results CYP2D6 rs28371725 polymorphism was associated with low MSF and increased SAA in severe hyposalivation (genotype relative risk: 12.75, 95% CI 1.45–112.12). Additionally, variants (rs28371706, rs5030655) were associated with high ADS scores. Individuals with reduced CYP2D6 activity presented with higher systemic exposure and a greater anticholinergic burden for a given dose, as reflected by higher ADS and SAA. CYP2C19 polymorphisms showed no strong associations with salivary outcomes or anticholinergic burden. Conclusion Genetic variation in CYP2D6 contributes to interindividual differences in systemic anticholinergic burden and hyposalivation. Pharmacogenetic profiling of CYP450 genes may help identify patients at risk of xerostomia from anticholinergic therapy, supporting more personalized and optimized anticholinergic prescribing.

  PublisherDOI

• Medication-Induced Xerostomia: Cross-Sectional Analysis of Salivary Flow, Intraoral Aching, and Anxiety

  Journal of Clinical Medicine · 2025-09-19 · 1 citations

  articleOpen access1st author

  Background: This cross-sectional study investigated the associations between medication-induced xerostomia (perceived oral dryness) and intraoral painful aching in 141 middle-aged adults (45–64 years) with self-reported xerostomia resulting from anticholinergic medications. Methods: Xerostomia severity, anxiety, and intraoral painful aching were evaluated using questionnaires, including the semiquantitative Xerostomia Inventory survey. Reduction in saliva secretion (hyposalivation) was objectively assessed by the measurement of unstimulated whole saliva (UWS) flow. Results: Multivariate stepwise linear regression was used to identify factors associated with XI scores, adjusting for potential confounders including age, sex, diabetes, smoking status, and race. The final model identified UWS flow (p = 0.0023), intraoral painful aching (p = 0.0030), and diabetes (p = 0.0097) as significant predictors of xerostomia severity. Anxiety demonstrated a marginal association (p = 0.0643) and accounted for a smaller proportion of model variance. Relative importance analysis revealed that UWS flow contributed 33.16% to the overall model fit, followed by intraoral pain (31.30%), diabetes (23.60%), and anxiety (11.93%). Conclusions: The findings indicate that reduced salivary flow, intraoral discomfort, and the presence of diabetes are significant contributors to xerostomia severity in individuals taking anticholinergic medications. These results highlight the importance of individualized evaluation in xerostomia care and inform targeted clinical strategies for managing xerostomia symptoms in patients with intraoral painful aching, anxiety, or comorbid diabetes.

  PublisherDOI

• C2230, A Selective, Use- And State-Dependent CaV2.2 Channel Blocker for Neuropathic, Orofacial, and Osteoarthritic Pain

  Journal of Pain · 2024-04-01

  articleOpen access
  PublisherOA PDFDOI

• Genetic Contributions to Pain Modulation in Sickle Cell: A Focus on Single Nucleotide Polymorphisms

  SSRN Electronic Journal · 2024-01-01

  preprintOpen accessSenior author
  PublisherDOI

• C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models

  Journal of Clinical Investigation · 2024-12-10 · 15 citations

  articleOpen access

  Antagonists - such as Ziconotide and Gabapentin - of the CaV2.2 (N-type) calcium channels are used clinically as analgesics for chronic pain. However, their use is limited by narrow therapeutic windows, difficult dosing routes (Ziconotide), misuse, and overdoses (Gabapentin), as well as a litany of adverse effects. Expansion of novel pain therapeutics may emerge from mechanism-based interrogation of CaV2.2. Here, we report the identification of C2230, an aryloxy-hydroxypropylamine, as a CaV2.2 blocker. C2230 trapped and stabilized inactivated CaV2.2 in a slow-recovering state and accelerated the open-state inactivation of the channel, conferring an advantageous use-dependent inhibition profile. C2230 inhibited CaV2.2 during high-frequency stimulation, while sparing other voltage-gated ion channels. C2230 inhibited CaV2.2 in dorsal root and trigeminal ganglia neurons from rats, marmosets, and humans in a G-protein-coupled-receptor-independent manner. Further, C2230 reduced evoked excitatory postsynaptic currents and excitatory neurotransmitter release in the spinal cord, leading to relief of neuropathic, orofacial, and osteoarthritic pain-like behaviors via 3 different routes of administration. C2230 also decreased fiber photometry-based calcium responses in the parabrachial nucleus, mitigated aversive behavioral responses to mechanical stimuli after neuropathic injury, and preserved protective pain responses, all without affecting motor or cardiovascular function. Finally, site-directed mutation analysis demonstrated that C2230 binds differently than other known CaV2.2 blockers, making it a promising lead compound for analgesic development.

  PublisherOA PDFDOI

• Post-Traumatic Trigeminal Neuropathy: Neurobiology and Pathophysiology

  Biology · 2024-03-04 · 9 citations

  articleOpen accessSenior authorCorresponding

  Painful traumatic trigeminal neuropathy (PTTN) is a chronic neuropathic pain that may develop following injury to the trigeminal nerve. Etiologies include cranio-orofacial trauma that may result from dental, surgical, or anesthetic procedures or physical trauma, such as a motor vehicle accident. Following nerve injury, there are various mechanisms, including peripheral and central, as well as phenotypic changes and genetic predispositions that may contribute to the development of neuropathic pain. In this article, we review current literature pertaining to the cellular processes that occur following traumatic damage to the trigeminal nerve, also called cranial nerve V, that results in chronic neuropathic pain. We examine the neurobiology and pathophysiology based mostly on pre-clinical animal models of neuropathic/trigeminal pain.

  PublisherOA PDFDOI

• Role of common and rare genetic variants in the aetiology of trigeminal neuralgia

  medRxiv · 2024-07-16

  preprintOpen access

  Summary Background Trigeminal neuralgia (TN) is characterized by repeated paroxysmal attacks of severe facial pain usually lasting 1-3 minutes. Lifetime prevalence is ca.3 per 1,000, more common in women, and with onset generally in middle age. Medications usually provide relief in the early stages of the disorder, but for many patients, severe drug side effects emerge and medically intractable pain returns, sometimes lasting for life. Some patients present with paroxysmal pain predominantly while others also experience substantial concomitant constant facial pain. Some patients have a history of a blood vessel compressing and damaging their trigeminal nerve (neurovascular compression, NVC). For these “classical” cases, surgery often provides complete or substantial pain relief for many years. “Idiopathic” cases without NVC or any other apparent cause also occur. NVC was previously observed to be less frequent in females who had early age of onset and these patients may constitute a unique subgroup. Our aim was to evaluate the role of inherited genetic variation in the aetiology of TN in patient subgroups based on age of onset, presence of NVC and sex. Methods To maximize aetiological homogeneity, only patients with predominantly paroxysmal pain and minimal concomitant continuous pain were included in the analysis. Conditions known to cause secondary TN such as tumors or multiple sclerosis were excluded. The GWAS analysis was based on 626 TN patients and 827 Control subjects of European ancestry recruited in Canada, the UK, and US. A Genome-Wide Association Study (GWAS) analysis was performed using Affymetrix’s Precision Medicine arrays yielding 7,781,254 biallelic DNA variants available after Quality Control (QC) and imputation. Rare damaging mutations in genes with functions relevant to the biology of TN were identified in Whole Genome Sequencing (WGS) genomic DNA of 100 patients using a novel strategy based on overlap of symptoms of TN with symptoms of known genetic disorders. Findings The GWAS analysis revealed associations at eight genome locations including near LRP1B (P-value 6.3 X 10 -15 ), a gene important for repair of myelin sheath injury that has been previously proposed as a target for the treatment of neuropathic pain. Associations were also found for the potassium channel gene KCNK10 , and for CHL1, CUX1, SGMS1 and ZNF804B genes, all genes with neural functions potentially relevant to the aetiology of TN. In addition, high-risk genotypes at the CUX1 and KCNK10 genes exhibit significant interactions with patients’ sex and the presence or absence of NVC (P-values 0.005 and 0.017, respectively). Whole genome sequencing of 100 TN patients revealed mutations in ion channel genes TRPM4 (six patients), SCN10A and SCNN1B (five patients), CACNA1F, CACNA1S and SCN5A (four patients) and CACNA1H , SCN2A and SCN9A (three patients). Female patients with onset prior to age 46 had more mutated genes with myelin-related functions (P-value 0.004) and associated with epilepsy or seizure (P-value 0.03) than older onset females and males of any onset age. Interpretation Risk of TN in patients presenting with paroxysmal pain only is associated with both common genetic variants and with rare mutations. Some high-risk genotypes have significant interactions with sex and NVC. Evidence of the condition’s heterogeneous genetic aetiology should be considered when evaluating novel therapies. Funding Grants from the William H. and Leila A. Cilker Genetics Research Program of the Facial Pain Research Foundation, The Foundation of the University of Medicine and Dentistry of New Jersey, and Rutgers School of Dental Medicine, Rutgers Health, Rutgers – The State University of New Jersey Contact Scott R Diehl, PhD, scott.diehl@rutgers.edu , 973-972-7053

  PublisherOA PDFDOI

• Genetic contributions to pain modulation in sickle cell: A focus on single nucleotide polymorphisms

  Gene Reports · 2024-07-18 · 2 citations

  articleOpen accessSenior authorCorresponding

  Background: Despite recent advances in our knowledge of genetic contributions to the highly variable sickle cell disease (SCD) phenotype, our understanding of genetic factors associated with pain sensitivity in SCD remains limited. Previous studies investigated specific variants in single candidate genes and their association with SCD pain variability. The primary aim of the current study was to expand the genes and polymorphisms tested to discover new risk genes (polymorphisms) associated with central sensitization for individuals with SCD. Methods: = 59, Mage = 36.8 ± 11.5, 65.8 % female) underwent quantitative sensory testing to examine central sensitization and general pain sensitivity. Participants reported average crisis and non-crisis pain intensities weekly using a 0-100 scale, and provided salivary samples for genotyping. The Hardy-Weinberg equilibrium was verified for controls, and allele distributions were tested with chi-square and odds ratio tests. The Benjamini-Hochberg procedure was used to control for false discovery rate. Regression analyses and Wilcoxon tests were used to test associations for normally distributed and skewed data, respectively. Results: Central sensitization and general pain sensitivity were not associated with hemoglobin genotype (Ps > 0.05). Of 4145 SNPs tested, following false discovery rate adjustments, 11 SNPs (rs11575839, rs12185625, rs12289836, rs1493383, rs2233976, rs3131787, rs3739693, rs4292454, rs4364, rs4678, rs6773307) were significantly associated with central sensitization, and one SNP (rs7778077) was significantly associated with average weekly non-crisis pain. No SNPs were associated with general pain sensitivity. Conclusions: These findings provide insights into genetic variants association with average non-crisis pain and central sensitization for individuals with SCD, and may provide support for genetic predictors of heightened pain experience within SCD.

  PublisherDOI

• Genetics Affecting the Prognosis of Dental Treatments

  Dental Clinics of North America · 2024-08-03 · 1 citations

  review1st author
  PublisherDOI

• Intranasal CRMP2-Ubc9 inhibitor regulates NaV1.7 to alleviate trigeminal neuropathic pain

  Pain · 2023-09-26 · 17 citations

  articleOpen access

  ABSTRACT: Dysregulation of voltage-gated sodium Na V 1.7 channels in sensory neurons contributes to chronic pain conditions, including trigeminal neuropathic pain. We previously reported that chronic pain results in part from increased SUMOylation of collapsin response mediator protein 2 (CRMP2), leading to an increased CRMP2/Na V 1.7 interaction and increased functional activity of Na V 1.7. Targeting this feed-forward regulation, we developed compound 194 , which inhibits CRMP2 SUMOylation mediated by the SUMO-conjugating enzyme Ubc9. We further demonstrated that 194 effectively reduces the functional activity of Na V 1.7 channels in dorsal root ganglia neurons and alleviated inflammatory and neuropathic pain. Here, we used a comprehensive array of approaches, encompassing biochemical, pharmacological, genetic, electrophysiological, and behavioral analyses, to assess the functional implications of Na V 1.7 regulation by CRMP2 in trigeminal ganglia (TG) neurons. We confirmed the expression of Scn9a , Dpysl2 , and UBE2I within TG neurons. Furthermore, we found an interaction between CRMP2 and Na V 1.7, with CRMP2 being SUMOylated in these sensory ganglia. Disrupting CRMP2 SUMOylation with compound 194 uncoupled the CRMP2/Na V 1.7 interaction, impeded Na V 1.7 diffusion on the plasma membrane, and subsequently diminished Na V 1.7 activity. Compound 194 also led to a reduction in TG neuron excitability. Finally, when intranasally administered to rats with chronic constriction injury of the infraorbital nerve, 194 significantly decreased nociceptive behaviors. Collectively, our findings underscore the critical role of CRMP2 in regulating Na V 1.7 within TG neurons, emphasizing the importance of this indirect modulation in trigeminal neuropathic pain.

  PublisherOA PDFDOI

Frequent coauthors

• Rafael Benoliel

  Rutgers, The State University of New Jersey

  42 shared

• Eli Eliav

  Eastman Chemical Company (United States)

  38 shared

• Junad Khan

  Eastman Chemical Company (United States)

  34 shared

• Scott R. Diehl

  Rutgers, The State University of New Jersey

  12 shared

• Cibele Nasri‐Heir

  12 shared

• Ching‐Yu Huang

  Kean University

  12 shared

• Fengshen Kuo

  11 shared

• Gary Heir

  11 shared

Labs

• Olga Korczeniewska LaboratoryPI