Browsing by Author "Shueb, Sarah"
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Item Bivalent Ligand MMG22 Reduces Bone Cancer Pain without Tolerance or Sedation(2022-07) Shueb, SarahPain is among the most common symptoms in cancer and approximately 90% of patients experience end-stage cancer pain. The management of cancer pain is challenging due to the significant side effects associated with opioids, and novel therapeutic approaches are needed. MMG22 is a bivalent ligand containing MOR agonist and mGluR5 antagonist pharmacophores joined by a 22-atom spacer. MMG22 exhibited extraordinary analgesia following intrathecal administration in a mouse model of bone cancer pain. Here, we assessed the effectiveness of systemic administration of MMG22 in reducing cancer pain and evaluated whether MMG22 displays side effects associated with opioids. Fibrosarcoma cells were injected into and around the calcaneus bone in C3H mice. Mechanical hyperalgesia was defined as an increase in the paw withdrawal frequencies (PWFs) evoked by the application of a von Frey monofilament (3.9 mN bending force) applied to the plantar surface of the hind paw.Subcutaneous (s.c.), intramuscular (i.m.), and oral (p.o.) administration of MMG22 produced robust dose-dependent antihyperalgesic, whose ED50 was orders of magnitude lower than morphine. Moreover, the ED50 for MMG22 decreased with disease progression. Importantly, s.c. administration of MMG22 did not produce acute (24 h) or long-term (9 days) tolerance, was not rewarding (conditioned place preference test), and did not produce naloxone-induced precipitated withdrawal or altered motor function. A possible mechanism of action of MMG22 is discussed in terms of inhibition of spinal NMDAR via antagonism of its co-receptor, mGluR5, and concomitant activation of neuronal MOR. We suggest that MMG22 may be a powerful alternative to traditional opioids for managing cancer pain.Item Comparing the oral health related quality of life in four orofacial pain conditions(2014-11) Shueb, SarahObjectives: Pain is known to reduce quality of life. Concurrently, it is believed that orofacial pain reduces the oral health-related quality of life (OHRQoL). While the impact that painful temporomandibular disorders (TMD) have on OHRQoL has been well described, little has been reported about the impact of acute dental pain (ADP). Moreover, the impact of trigeminal neuralgia (TN) and persistent dentoalveolar pain disorder (PDAP) on OHRQoL has not been reported yet. The aim of this study was, therefore, to compare the OHRQoL impairment among four orofacial pain conditions, i.e., participant with TMD, ADP, TN, and PDAP and compare the results with people without orofacial pain. Methods: OHRQoL was measured using the OHIP-49 questionnaire, using a convenience sample of four orofacial pain conditions (pain groups with TMD (n=30), ADP (n=27), TN (n=21), PDAP (n=16)). To provide a frame of reference for pain-related OHRQoL impairment, we also included a group of pain-free control participants (n=20). The mean OHIP-49 summary score, with its 95% confidence interval (95% CI), described the level of impact. The differences in mean values across the four pain conditions were analyzed using Analysis of Variance (ANOVA). The second part of the analysis was performed by comparing the OHIP-49 mean score of each condition and the OHIP mean score of the control group using Student's two sample t-test. Finally the absolute score differences between groups were judged according to: the Minimal Important Difference (MID) and the Effect sizes (ES).Results: OHRQoL was measured using OHIP-49 in a convenience sample of four conditions (patient groups with orofacial pain; TMD (n=30), acute dental pain (n=27), TN (n=21), PDAP (n=16)). Our results showed significant impairment in the OHRQoL for the four conditions compared to the control group. The mean OHIP-49 score (95% CI) was 60.8 (48-74) for TMD, 61 (48-74) for ADP, 58 (41-75) for TN, and 66 (46-86) for PDAP. For comparison purposes, the mean OHIP-49 score (95% CI) was 8 (3-13) for the pain free group. The difference was statistically significant and clinically relevant between pain groups and the control group (all comparisons: P<0.001). Each of the four orofacial pain conditions had similar levels of impact on the OHRQoL when compared to each other. Using the Minimum Important Deference (MID) there was a clinical significance between chronic conditions (TMD, TN, PDAP) and the ADP (11 (-6 to 28), 8.4 (-11 to 28), and 17(-4 to 37)) respectively, also a clinical significance between the four orofacial conditions and the control group was detected. A moderate effect size was detected between participants with PDAP and ADP (ES=0.5, 95%CI (-0.1 to 1.1)). Conclusion: Our data supported the hypothesis that orofacial pain conditions have a substantial impact and adversely affect the quality of life of participants with four orofacial pain conditions as compared to those with no pain.