• Determining the Neural Correlates of Burning Mouth Syndrome

      Payano Sosa, Janell; Seminowicz, David A.; 0000-0003-1337-3749 (2020)
      In the United States, nearly 1 million people suffer from burning mouth syndrome (BMS), a chronic orofacial pain condition that is largely unrecognized by the medical community and predominantly affects post- and peri-menopausal women. Relatively little in-depth research is available on the condition, and patients often give up seeking treatment. The pain in BMS arises spontaneously (i.e. in the absence of stimuli), but the mechanisms of this spontaneous pain is unclear, and there is limited research on structural and functional brain changes that may occur in a BMS sufferer. The goal of this dissertation was to investigate the central nervous system mechanisms of pain experienced in BMS. We collected: 8-day diaries, morning and afternoon quantitative sensory testing of both orofacial and forearm regions; afternoon structural and functional MRIs, and questionnaires from 27 BMS patients and 33 healthy post-menopausal women. Our hypotheses that, compared to healthy participants BMS patients have: higher pain sensitivity, especially in orofacial regions during the afternoon; lower grey matter volume and higher functional connectivity in nociceptive pathways associated with noxious heat during rest and evoked thermal pain, even after accounting for anxiety, were not supported. Instead, we found a time-of-day-dependent effect during warm detection and cold detection of face and forearm; lower grey matter volume of the dorsolateral prefrontal cortex (DLPFC), and higher grey matter volume of the inferior temporal gyrus and parabrachial nucleus (PBN); lower PBN connectivity with the DLPFC and primary somatosensory cortex (S1); higher connectivity of the right lateral hypothalamus (LH) with posterior insula during warm condition; connectivity of right medial hypothalamus and LH to left DLPFC and right PBN to bilateral S1 not associated with anxiety in BMS compared to healthy participants. Altogether, BMS showed abnormal responses to innocuous stimuli. This was supported by fMRI data, where connectivity differences were mostly present during innocuous stimulation. These altered sensory and brain responses could reflect heightened anticipation of thermal stimuli (both pain-specific and non-pain specific) associated with disruption of communication between regions associated with negative affect of pain (insula), attention modulation of pain (left DLPFC), somatosensation (S1), and thermoregulation (LH and PBN).
    • Efficacy of Acute Pain Management on Chronic Pain Following Lower Extremity Trauma

      Griffioen, Mari Anne; Renn, Cynthia L.; 0000-0002-7449-052X (2015)
      Background: Many patients with traumatic injuries report chronic pain, with injuries to the lower extremity resulting in higher rates than other sites. High pain intensity at the time of injury is a risk factor for chronic pain, but it is not clear what specific acute pain patterns following injury influence the development of chronic pain. In addition, it is not known whether chronic pain in this patient population includes symptoms of heightened sensitivity to innocuous and noxious stimuli, which have been reported in other chronic pain conditions. Purpose: To examine the relationship between post-trauma acute pain status and the incidence of chronic pain, and to test for hypo- or hypersensitivity to innocuous and noxious thermal and mechanical stimuli in patients with lower extremity traumatic injuries. Methods: This was a descriptive retrospective cohort study with a cross-sectional component. Patients were contacted by telephone and their pain related to the injury site was assessed. This was followed by a retrospective medical chart review. A sub-sample of patients and healthy controls also underwent sensory testing. Results: In this study 54% of patients experienced no improvement in pain during hospitalization. The mean pain score was higher for patients with chronic pain (78%) compared to patients with no chronic pain (5.1 vs. 4.2), but there were no significant difference between the group based on the pain trajectory. Patients with injuries had higher warmth detection threshold (36.5 vs. 33.2), and current perception threshold (CPT) stimulus-response at 2000 Hz (292 vs. 122) and 250 Hz (76 vs. 35) compared to healthy controls. Conclusion: Consistent with other studies, high pain intensity at the time of injury was associated with chronic pain. The increased warmth perception threshold and increased CPT stimulus-response in cases suggest hypoesthetic nerve function. This is the first study to conduct an in-depth analysis of acute pain intensity patterns and sensory function in patients with traumatic lower extremity injuries and will guide the design of a future longitudinal study.
    • The Use of Current Perception Threshold for the Assessment of Oxaliplatin-Induced Peripheral Neuropathy

      Akpadiaha, Israel Ndueso; Griffith, Kathleen A.; 0000-0003-3661-1148 (2016)
      Background: Colorectal cancer (CRC) is a common malignancy, and up to 80% of patients diagnosed receive chemotherapy. Oxaliplatin is the principal chemotherapy agent for the treatment of CRC, and yet the associated oxaliplatin-induced peripheral neuropathy (OIPN) affects sensory fibers and is a treatment-limiting factor. OIPN reduces quality of life (QoL) and is associated with neuropathic pain (NP). As no effective treatment is available, improved early assessment of OIPN is needed. Current perception threshold (CPT) is a promising approach that uses sine-wave current electrical stimulus delivered at specific frequencies to elicit responses from peripheral nerves and may aid in OIPN identification. Purpose: The purpose of this study was threefold: 1) to compare CPT with validated quantitative sensory testing (QST) clinical tests in assessing sensory fiber function; 2) to compare CPT with provider administered National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTC-AE) for identification of OIPN; and 3) to describe the relationship between NP measured by Neuropathic Pain Scale (NPS) and QST and their differential impact on QoL (FACT-G). Methods: A correlational descriptive design was used and a secondary analysis conducted using data from the Genetic Correlates of OIPN study. A total of 19 participants were enrolled and assessed at baseline, following 500mg/m2 of oxaliplatin, and upon oxaliplatin completion. Bivariate linear mixed models were used to account for repeated assessments clustered within patients. Results: An association between certain QST measures and CPT 2000Hz was identified (Vibration: =-44.55, p=0.045; mechanical detection: =269.59, p=0.008). CPT 2000 Hz and 250 Hz were associated with warm detection threshold (=9.0, p=0.030 and =4.24, p=0.027, respectively). There was also a positive association between neuropathic pain severity (NPS) and QoL [FACT-G (=0.276, p<0.016)]. Conclusion: The association between CPT and currently documented methods of OIPN assessment was limited. Furthermore, the positive association between NP and QoL requires additional exploration as it contradicts published data. Larger studies are needed to explore further if CPT is useful for assessment of OIPN.