David A Bereiter

University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

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Publications (105)329.15 Total impact

  • Estephan J Moana-Filho · David A Bereiter · Donald R Nixdorf ·
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    ABSTRACT: Aims: (1) To determine the brain regions activated by dentoalveolar pressure stimulation in persistent dentoalveolar pain disorder (PDAP) patients, and (2) to compare these activation patterns to those seen in pain-free control subjects. Methods: A total of 13 PDAP patients and 13 matched controls completed the study. Clinical pain characteristics and psychosocial data were collected. Dentoalveolar mechanical pain thresholds were determined with a custom-made device over the painful area for patients and were used as the stimulation level during functional magnetic resonance imaging (fMRI) data acquisition. Control subjects received two stimulation levels over matched locations during fMRI scanning: one determined (as above) that evoked equally subjective pain ratings matching those of patients (subjective-pain match) and another nonpainful stimulation level matching the average stimulus intensity provided to patients (stimulus-intensity match). Clinical and psychosocial data were analyzed using independent samples t tests, Mann-Whitney U test, and Spearman rank-order correlation coefficient. fMRI data were analyzed using validated neuroimaging software and tested using a general linear model. Results: PDAP patients had greater anxiety (P < .0001) and depression scores (P = .001), more jaw function impairment (P < .0001), and greater social impact (P < .0001) than controls. No significant differences were found for brain activation spatial extent (PDAP X Controls subjective pain: P = .48; PDAP X Controls stimulus intensity: P = .12). Brain activations were significantly increased for PDAP patients compared to control subjects when matched to stimulus intensity in several regions related to the sensory-discriminative and cognitive components of pain perception, including the primary and secondary somatosensory cortices, inferior parietal lobule, insula, premotor cortex, prefrontal cortex, and thalamus. When matched to subjective pain ratings, increased brain activations were still present for PDAP patients compared to controls, although to a lesser extent. Conclusion: The present results suggest that dentoalveolar pressure is processed differently in the brain of PDAP patients, and the increased activation in several brain areas is consistent with amplified pain processing.
    10/2015; 29(4):349-362. DOI:10.11607/ofph.1463
  • Akimasa Tashiro · Yasuhiro Nishida · David A Bereiter ·
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    ABSTRACT: Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are functionally linked to estrogen receptors and play a key role in the plasticity of central neurons. Estrogen status strongly influences sensory input from the temporomandibular joint (TMJ) to neurons at the spinomedullary (Vc/C1-2) region. This study tested the hypothesis that TMJ input to Vc/C1-2 neurons involved group I mGluR activation and depended on estrogen status. TMJ-responsive neurons were recorded in superficial laminae at the Vc/C1-2 region in ovariectomized (OvX) female rats treated with low-dose estradiol (2 μg/day, LE) or high-dose estradiol (20 μg/day, HE) for 2 days. TMJ-responsive units were activated by adenosine triphosphate (ATP, 1 mM) injected into the joint space. Receptor antagonists selective for mGluR1 (CPCCOEt) or mGluR5 (MPEP) were applied topically to the Vc/C1-2 surface at the site of recording 10 min prior to the intra-TMJ ATP stimulus. In HE rats, CPCCOEt (50 and 500 μM) markedly reduced ATP-evoked unit activity. By contrast, in LE rats, a small but significant increase in neural activity was seen after 50 μM CPCCOEt, while 500 μM caused and a large reduction in activity that was similar in magnitude as that seen in HE rats. Local application of MPEP produced a significant inhibition of TMJ-evoked unit activity independent of estrogen status. Neither mGluR1 or mGluR5 antagonism altered the spontaneous activity of TMJ units in HE nor LE rats. High dose MPEP caused a small reduction in the size of the convergent cutaneous receptive field in HE rats, while CPCCOEt had no effect. These data suggest that group I mGluRs play a key role in sensory integration of TMJ nociceptive input to the Vc/C1-2 region and are largely independent of estrogen status. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 04/2015; 299. DOI:10.1016/j.neuroscience.2015.04.051 · 3.36 Impact Factor
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    ABSTRACT: Repeated forced swim (FS) conditioning enhances nociceptive responses to temporomandibular joint (TMJ) stimulation in male and female rats. The basis for FS-induced TMJ hyperalgesia remains unclear. To test the hypothesis that serotonin 3 receptor (5HT3R) mechanisms contribute to enhanced TMJ nociception after FS, ovariectomized female rats were treated with estradiol and subjected to FS for three days. On day 4, rats were anesthetized with isoflurane and TMJ-responsive neurons were recorded from superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical (Vc/C1-2) region and electromyographic (EMG) activity was recorded from the masseter muscle. Only Vc/C1-2 neurons activated by intra-TMJ injections of ATP were included for further analysis. Although neurons in both superficial and deep laminae were activated by ATP, only neurons in deep laminae displayed enhanced responses after FS. Local application of the 5HT3R antagonist, ondansetron (OND), at the Vc/C1-2 region reduced the ATP-evoked responses of neurons in superficial and deep laminae and reduced the EMG response in both sham and FS rats. OND also decreased the spontaneous firing rate of neurons in deep laminae and reduced the high threshold convergent cutaneous receptive field area of neurons in superficial and deep laminae in both sham and FS rats. These results revealed that central application of a 5HT3R antagonist, had widespread effects on the properties of TMJ-responsive neurons at the Vc/C1-2 region and on jaw muscle reflexes under sham and FS conditions. It is concluded that 5HT3R does not play a unique role in mediating stress-induced hyperalgesia related to TMJ nociception. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 04/2015; 299. DOI:10.1016/j.neuroscience.2015.04.037 · 3.36 Impact Factor
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    ABSTRACT: Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg) and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, while OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline-evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared to controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.
    Pain 02/2015; 156(5). DOI:10.1097/j.pain.0000000000000135 · 5.21 Impact Factor
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    ABSTRACT: Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil, a TRPA1 agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. Mustard oil (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of mustard oil (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. Mustard oil caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by mustard oil. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 01/2015; 290. DOI:10.1016/j.neuroscience.2015.01.046 · 3.36 Impact Factor
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    ABSTRACT: The rostral ventromedial medulla (RVM) projects to the medullary and spinal dorsal horns and is a major source of descending modulation of nociceptive transmission. Traditionally, neurons in the RVM are classified functionally as ON, OFF and NEUTRAL cells based on responses to noxious cutaneous stimulation of the tail or hind paw. ON cells facilitate nociceptive transmission, OFF cells are inhibitory, whereas NEUTRAL cells are unresponsive to noxious stimuli and their role in pain modulation is unclear. Classification of RVM neurons with respect to stimulation of craniofacial tissues is not well defined. In isoflurane-anesthetized male rats, RVM neurons first were classified as ON (25.5%), OFF (25.5%) or NEUTRAL cells (49%) by noxious tail pinch. Pinching the skin overlying the temporomandibular joint (TMJ) altered the proportions of ON (39.2%) and OFF (42.2%) and NEUTRAL cells (19.6%). To assess the response of RVM cells to specialized craniofacial inputs, adenosine triphosphate (ATP; 0.01-1 mM) was injected into the TMJ (0.01-1 mM ATP) and capsaicin (0.1%) was applied to the ocular surface. TMJ and ocular surface stimulation also resulted in a reduced proportion of NEUTRAL cells compared to tail pinch. Dose-effect analyses revealed that ON and OFF cells encoded the intra-TMJ concentration of ATP. These results suggest that somatotopy plays a significant role in the functional classification of RVM cells and support the notion that NEUTRAL cells likely are sub-groups of ON and OFF cells. It is suggested that a portion of RVM neurons serves different functions in modulating craniofacial and spinal pain conditions.
    Journal of Neurophysiology 09/2014; 113(1). DOI:10.1152/jn.00125.2014 · 2.89 Impact Factor
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    ABSTRACT: Cornea-evoked eyeblinks maintain tear film integrity on the ocular surface in response to dryness and protect the eye from real or potential damage. Eyelid movement following electrical stimulation has been well studied in humans and animals; however, the central neural pathways that mediate protective eyeblinks following natural nociceptive signals are less certain. The aim of this study was to assess the role of the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/upper cervical cord (Vc/C1) junction regions on orbicularis oculi electromyographic (OOemg) activity evoked by ocular surface application of hypertonic saline or exposure to bright light in urethane anesthetized male rats. The Vi/Vc and Vc/C1 regions are the main sites of termination for trigeminal afferent nerves that supply the ocular surface, while hypertonic saline (saline = 0.15-5M) and bright light (light = 5-20k lux) selectively activate ocular surface and intraocular trigeminal nerves, respectively, and excite second-order neurons at the Vi/Vc and Vc/C1 regions. Integrated OOemg activity, ipsilateral to the applied stimulus, increased with greater stimulus intensities for both modalities. Lidocaine applied to the ocular surface inhibited OOemg responses to hypertonic saline, but did not alter the response to light. Lidocaine injected into the trigeminal ganglion blocked completely the OOemg responses to hypertonic saline and light indicating a trigeminal afferent origin. Synaptic blockade by cobalt chloride of the Vi/Vc or Vc/C1 region greatly reduced OOemg responses to hypertonic saline and bright light. These data indicate that OOemg activity evoked by natural stimuli known to cause irritation or discomfort in humans depends on a relay in both the Vi/Vc transition and Vc/C1 junction regions.
    Neuroscience 07/2014; 277. DOI:10.1016/j.neuroscience.2014.07.052 · 3.36 Impact Factor
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    ABSTRACT: Objective: To determine if estradiol (E2) is synthesized by brainstem neurons responsive temporomandibular joint (TMJ) stimulation. Method: Preclinical evidence suggests that E2 can act rapidly to alter pain-like behavior. This study used immunohistochemical (IHC) and microdialysis methods to determine if: 1) E2 is synthesized by trigeminal caudalis (Vc) neurons responsive to TMJ stimulation, 2) sex differences exist for E2 synthesis in Vc, and 3) if TMJ stimulation alters E2 levels in Vc. For IHC, male and female (n = 4/group) rats were anesthetized with pentobarbital and received intra-TMJ injection of the TRPA1 agonist, mustard oil (MO, 20%), or vehicle. Brainstem sections were processed for Fos protein (neuronal activity marker), aromatase (E2 biosynthetic enzyme) and E2 receptor (ERa). Microdialysis samples (30 min) were collected from Vc under isoflurane. The aromatase inhibitor, Anastrozole (100µM), was delivered via the dialysis probe and topically to the Vc surface. Result: Cells counts in Vc revealed 20-25% of Fos+ neurons were aromatase+ in males and females after TMJ stimulation. By contrast, the % of Fos/ERa Vc neurons was greater in females than males (41% vs 21%, p<0.025). Microdialysis results revealed: 1) similar E2 levels in Vc of intact males and females, 2) gonadectomy reduced E2 in Vc by 20% in males and 40% in females, 3) aromatase inhibition transiently reduced E2 by 40-50%, and 4) E2 levels in Vc increased >50% after intra-TMJ injection of MO. Conclusion: E2 is synthesized by Vc neurons that encode noxious sensory signals from the TMJ. The greater density of ERa in Vc of females than males predicts that locally released E2 has a greater effect on neural activity in females. The function of E2 synthesis in Vc may be to fine tune synaptic activity in the brain driven by input from trigeminal sensory neurons.
    IADR General Session and Exhibition 2014; 06/2014
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    ABSTRACT: Orexin-A (OxA) is synthesized in posterior and lateral regions of the hypothalamus and contributes to homeostatic regulation of body functions including pain modulation. To determine if orexinergic mechanisms contribute to posterior hypothalamus (PH)-induced modulation of ocular input to subnucleus caudalis/upper cervical (Vc/C1) neurons, the orexin-1 receptor antagonist SB334867 was applied to the dorsal brainstem surface prior to PH disinhibition, by bicuculline methiodide, in male rats under isoflurane anesthesia. Ocular input to Vc/C1 units by bright light or hypertonic saline was markedly reduced by PH disinhibition and reversed completely by local Vc/C1 application of SB334867. OxA applied to the Vc/C1 surface mimicked the effects of PH disinhibition in a dose-dependent manner. OxA-induced inhibition was prevented by co-application of SB334867, but not by the orexin-2 receptor antagonist TCS Ox2 29. PH disinhibition and local OxA application also reduced the high threshold convergent cutaneous receptive field area of ocular units, suggesting widespread effects on somatic input to Vc/C1 ocular units. Vc/C1 application of OxA or SB334867 alone did not affect the background discharge of ocular units and suggested that the PH-OxA influence on ocular unit activity was not tonically active. Vc/C1 application of OxA or SB334867 alone also did not alter mean arterial pressure, whereas PH disinhibition evoked prompt and sustained increases. These results suggest that stimulus-evoked increases in PH outflow acts through OxA and orexin-1 receptors to alter the encoding properties of trigeminal brainstem neurons responsive to input from the ocular surface and deep tissues of the eye.
    European Journal of Neuroscience 06/2014; 40(4). DOI:10.1111/ejn.12635 · 3.18 Impact Factor
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    ABSTRACT: Objective: Temporomandibular muscle and joint disorders (TMJD) are classified by spontaneous and/or chronic pain in the temporomandibular joint (TMJ) and masticatory muscles. Two key risk factors for the development of TMJD include estrogen status and psychological stress. Previous anatomical evidence suggested local production of estradiol in the Vc/C1-2 region of the brainstem. The aim of this study was to determine if TMJ stimulation and psychophysical stress affected local estradiol levels at the Vc/C1-2region. Method: A microdialysis probe (240µm o.d., 1 mm length) was positioned in the Vc/C1-2region of ovariectomized rats to collect extracellular fluid samples. Rats received daily doses of estradiol (30µg/kg) and subjected to forced swim (FS) conditioning for 3 days prior to microdialysis sampling. Dialysate samples were collected every 30 min (2 µl/min). Rats received an intra-TMJ injection of mustard oil (MO) or mineral oil (Control) under FS or naive conditions. Estradiol concentrations were measured by an ELISA assay. Result: Estradiol concentrations increased after intra-TMJ injection of MO, but not after mineral oil, in naive and FS rats. However, FS conditioning did not affect estradiol concentrations in dialysate samples. Conclusion: These results indicated that intra-TMJ stimulation with MO caused an increase in local production of estradiol in the Vc/C1-2 region. These data suggest that local production of estradiol may play a significant role in processing noxious sensory signals relevant for TMJ pain. Study Supported by a Grant from the National Institute of dental and Craniofacial Research: DI12758 (DAB) and the Office of Research on Women’s Health and the UMSOD Summer Fellowship program.
    AADR Annual Meeting & Exhibition 2014; 03/2014
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    European Journal of Neuroscience 01/2014; · 3.18 Impact Factor
  • Akimasa Tashiro · David A Bereiter · Randall Thompson · Yasuhiro Nishida ·
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    ABSTRACT: Sensory input from the temporomandibular joint (TMJ) to neurons in superficial laminae at the spinomedullary (Vc/C1-2) region is strongly influenced by estrogen status. This study determined if GABAergic mechanisms play a role in estrogen modulation of TMJ nociceptive processing in ovariectomized female rats treated with high (HE) or low dose (LE) estradiol (E2) for two days. Superficial laminae neurons were activated by ATP (1 mM) injections into the joint space. The selective GABAA receptor antagonist, bicuculline methiodide (BMI, 5 or 50 μM, 30 μl), applied at the site of recording greatly enhanced the magnitude and duration of ATP-evoked responses in LE rats, but not in units from HE rats. The convergent cutaneous receptive field (RF) area of TMJ neurons was enlarged after BMI in LE but not HE rats, while resting discharge rates were increased after BMI independent of estrogen status. By contrast, the selective GABAA receptor agonist, muscimol (50 μM, 30 μl), significantly reduced the magnitude and duration of ATP-evoked activity, resting discharge rate, and cutaneous RF area of TMJ neurons in LE and HE rats, whereas lower doses (5 μM) affected only units from LE rats. Protein levels of GABAA receptor β3 isoform at the Vc/C1-2 region were similar for HE and LE rats. These results suggest that GABAergic mechanisms contribute significantly to background discharge rates and TMJ-evoked input to superficial laminae neurons at the Vc/C1-2 region. Estrogen status may gate the magnitude of GABAergic influence on TMJ neurons at the earliest stages of nociceptive processing at the spinomedullary region.
    Neuroscience 12/2013; 259. DOI:10.1016/j.neuroscience.2013.11.053 · 3.36 Impact Factor
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    ABSTRACT: This report characterises the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens related discomfort. While there is limited evidence for the mechanisms involved in contact lens related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the impact of hyperosmolarity on ocular surface nociceptors and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented here to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactoral, including components of osmolarity, solution effects, desication, thermal effects, inflammation, friction and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva as well as the cornea.
    Investigative ophthalmology & visual science 09/2013; 54(11). DOI:10.1167/iovs.13-13226 · 3.40 Impact Factor
  • Ayano Katagiri · Keiichiro Okamoto · Randall Thompson · David A Bereiter ·
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    ABSTRACT: Enhanced light sensitivity is a common feature of many neuro-ophthalmic conditions and some chronic headaches. Previously we reported that the bright light-evoked increases in trigeminal brainstem neural activity and lacrimation depended on a neurovascular link within the eye (Okamoto et al., 2012). However, the supraspinal pathways necessary for these light-evoked responses are not well defined. To assess the contribution of the posterior hypothalamic area (PH), a brain region closely associated with control of autonomic outflow, we injected bicuculline methiodide (BMI), a GABAa receptor antagonist, into the PH and determined its effect on the encoding properties of ocular neurons at the ventrolateral trigeminal interpolaris/caudalis transition (Vi/Vc) and caudalis/upper cervical cord junction (Vc/C1) regions and on reflex lacrimation in male rats under isoflurane anesthesia. BMI markedly reduced light-evoked (> 80%) responses of Vi/Vc and Vc/C1 neurons at 10 min with partial recovery by 50 min after injection. BMI also reduced (> 35%) the convergent cutaneous receptive field area of Vi/Vc and Vc/C1 ocular neurons indicating that both intra-ocular and periorbital cutaneous inputs were affected by changes in PH outflow. Light-evoked lacrimation was reduced by > 35% at 10 min after BMI, while resting mean arterial pressure increased promptly and remained elevated (> 20 mmHg) throughout the 50 min post-injection period. These results suggested that PH stimulation, acting in part through increased sympathetic activity, significantly inhibited light- and facial skin-evoked activity of ocular neurons at the Vi/Vc and Vc/C1 region. These data provide further support for the hypothesis that autonomic outflow plays a critical role in mediating light-evoked trigeminal brainstem neural activity and reflex lacrimation.
    Neuroscience 04/2013; 246. DOI:10.1016/j.neuroscience.2013.04.053 · 3.36 Impact Factor
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    ABSTRACT: Objective: Low frequency stimulation of peripheral nerves at adequate intensities often results in increased pain sensation and is mediated by central neural processes. Intraoral pain is mediated by trigeminal nerves; however, little is known regarding temporal summation of pain and intraoral stimulus parameters. This study assessed the effects of repeated stimulation of the gingiva on pain sensation in subjects using a device adapted for use in functional imaging environments. Measurement of psychophysical responses provide behavioral context for future investigations of intraoral pain processing using functional imaging methods. Method: A previously modified fMRI-compatible device was used to deliver punctate pressure-pain stimuli to gingiva apical of the maxillary right premolars. Data was collected from healthy female subjects (n = 24, mean age of 31 year). Mildly painful baseline pressure (1/10 intensity) was determined for each subject prior to temporal summation protocol. The summation protocol consisted of 6 runs of 10 mild pressure-pain stimuli with 3 different inter-stimulus intervals (ISI), which were 2, 5, and 10 seconds in duration, in a randomized block design. Data were analyzed by a two-way repeated measures analysis of variance. Result: For each ISI, reported pain ratings increased significantly from the first to tenth individual stimuli (p<0.0001). The increase in pain ratings at 2 second ISI was significantly higher than at 5 and 10 second ISIs (p<0.0001 for both). The reported pain increased during individual trials with greater pain intensity ratings occurring with runs that had shorter ISI duration suggests temporal summation occurred (Trial-by-ISI interaction p<0.0001). Conclusion: Pain ratings increased with stimulation of the gingiva in a frequency-dependent manner, in a similar fashion as observed by others. Experimental paradigm has acceptable properties to proceed with future experiments will rate pain sensation to intraoral stimulation while simultaneous high-resolution fMRI is used to assess brainstem activation.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
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    Keiichiro Okamoto · Randall Thompson · Ayano Katagiri · David A Bereiter ·
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    ABSTRACT: Estrogen status and psychological stress contribute to the expression of several chronic pain conditions including temporomandibular muscle and joint disorders (TMJD). Sensory neurons that supply the temporomandibular joint (TMJ) region terminate in laminae I and V of the spinal trigeminal nucleus (Vc/C1-2 region); however, little is known about lamina-specificity and environmental influences on the encoding properties of TMJ brainstem neurons. To test the hypothesis that Vc/C1-2 neurons integrate both interoceptive and exteroceptive signals relevant for TMJ nociception, we recorded TMJ-evoked activity in superficial and deep laminae of ovariectomized rats under high and low estradiol (E2) and stress conditions. Rats received daily injections of low (LE) or high (HE) dose E2 and were subjected to forced swim (FS) or sham swim conditioning for 3days. The results revealed marked lamina-specificity in that HE rats displayed enhanced TMJ-evoked activity in superficial, but not deep, laminae independent of stress conditioning. By contrast, FS conditioned rats displayed increased background firing and TMJ-evoked activity of neurons in deep, but not superficial, laminae independent of E2 status. FS also enhanced TMJ-evoked masseter muscle activity and suggested the importance of deep dorsal horn neurons in mediating evoked jaw muscle activity. In conclusion, E2 status and psychophysical stress play a significant role in modifying the encoding properties of TMJ-responsive medullary dorsal horn neurons with a marked lamina-specificity.
    Pain 03/2013; 154(7). DOI:10.1016/j.pain.2013.03.009 · 5.21 Impact Factor
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    ABSTRACT: Abnormal sensitivity to bright light can cause discomfort or pain and evoke protective reflexes such as lacrimation. Although the trigeminal nerve is probably involved, the mechanism linking luminance to somatic sensory nerve activity remains uncertain. This study determined the effect of bright light on second-order ocular neurons at the ventral trigeminal interpolaris/caudalis transition (Vi/Vc) region, a major termination zone for trigeminal sensory fibers that innervate the eye. Most Vi/Vc neurons (80.9%) identified by responses to mechanical stimulation of the ocular surface also encoded bright light intensity. Light-evoked neural activity displayed a long latency to activation (> 10 s) and required transmission through the trigeminal root ganglion. Light-evoked neural activity was inhibited by intravitreal injection of phenylephrine or l-N(G) -nitro-arginine methyl ester (L-NAME), suggesting a mechanism coupled to vascular events within the eye. Laser Doppler flowmetry revealed rapid light-evoked increases in ocular blood flow that occurred prior to the increase in Vi/Vc neural activity. Synaptic blockade of the Vi/Vc region by cobalt chloride prevented light-evoked increases in tear volume, whereas blockade at the more caudal spinomedullary junction (Vc/C1) had no effect. In summary, Vi/Vc neurons encoded bright light intensity and were inhibited by drugs that alter blood flow to the eye. These results support the hypothesis that light-responsive neurons at the Vi/Vc transition region are critical for ocular-specific functions such as reflex lacrimation, whereas neurons at the caudal Vc/C1 junction region probably serve other aspects of ocular nociception.
    European Journal of Neuroscience 09/2012; 36(11). DOI:10.1111/j.1460-9568.2012.08272.x · 3.18 Impact Factor
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    ABSTRACT: Objective: Painful temporal summation is thought to be a centrally mediated phenomenon resulting in increased pain intensity produced by repeated stimuli. People with chronic pain conditions have shown increased temporal summation compared to pain-free controls, suggesting altered central nociceptive regulation. Functional 3-Tesla MRI research comparing pain-free controls to Persistent Dento-alveolar Pain disorder patients demonstrated differences in central processing, with large group-wise differences observed within the brainstem. We tested the redeveloped intraoral stimulus device to assess whether temporal summation from gingival pressure-pain stimuli can be obtained. Method: The MRI-compatible stimulus device was designed to provide dynamic, punctate, gingival pressure ranging from barely perceivable to severely painful. Chair-side device testing established individual thresholds of mild pressure-pain intensity. Temporal summation testing consisted of 6 runs of 10 consecutive, mildly painful stimuli separated by an inter-stimulus interval (ISI) of 2, 5, or 10 seconds for a given run. Perception of pain intensity was continually measured throughout each run. A 3 minute rest period was interposed between runs to reduce the potential for order effects. Data was analyzed by a three-way repeated measures analysis of variance. Result: Five healthy female subjects were tested (mean age: 32 years). Pain ratings significantly increased with repeated stimuli (P<0.005), and there was a significant trial and ISI interaction (P<0.001). Bonferroni-corrected t-tests showed greater temporal summation at ISI of 2 seconds than 10 seconds (P<0.005), and at 2 second ISI averaged pain intensity ratings for the tenth stimulus were significantly greater than for the first stimulus (P<0.005). Investigation of an order effect revealed no main interaction. Conclusion: An MRI-compatible intraoral stimulus device capable of producing painful temporal summation was developed. The next step is 7-Tesla MRI testing to produce functional maps of the brainstem to explore central processing of trigeminal-mediated pain.
    IADR General Session 2012; 06/2012
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    ABSTRACT: Psychological stress is a risk factor for the development of musculoskeletal pain of the head and neck; however, the basis for this relationship remains uncertain. This study tested the hypothesis that psychophysical stress alone was sufficient to alter the encoding properties of spinomedullary dorsal horn neurons and masseter muscle activity in male rats. Repeated forced swim conditioning increased markedly both the background firing rate and temporomandibular joint (TMJ)-evoked activity of neurons in deep dorsal horn, while neurons in superficial laminae were less affected. Stress also increased the responses to stimulation of facial skin overlying the TMJ of neurons in deep and superficial dorsal horn. TMJ-evoked masseter muscle activity was enhanced significantly in stressed rats, an effect that was reduced by prior blockade of the spinomedullary junction region. These data indicated that repeated psychophysical stress induced widespread effects on the properties of medullary dorsal horn neurons and masseter muscle activity. The effects of stress were seen preferentially on neurons in deep dorsal horn and included enhanced responses to chemosensory input from the TMJ and mechanical input from overlying facial skin. The stress-induced elevation in TMJ-evoked masseter muscle activity matched well with the changes seen in dorsal horn neurons. It is concluded that the spinomedullary junction region plays a critical role in the integration of psychophysical stress and sensory information relevant for nociception involving deep craniofacial tissues.
    European Journal of Neuroscience 04/2012; 36(1):2025-34. DOI:10.1111/j.1460-9568.2012.08100.x · 3.18 Impact Factor
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    Z Chang · K Okamoto · D.A. Bereiter ·
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    ABSTRACT: Several craniofacial pain conditions, including temporomandibular joint disorders (TMJDs), are more prevalent in women than men. The basis for sex differences in deep craniofacial pain is not known. The present study compared the magnitude of ascending projections from temporomandibular joint (TMJ)-responsive neurons in trigeminal brainstem with the ventrolateral periaqueductal gray (vlPAG) or posterior nucleus of the thalamus (Po) in males and female rats. Fluorogold (FG) was injected into vlPAG or Po, and TMJ-responsive neurons were identified by Fos-like immunoreactivity (Fos-LI) after mustard oil injection. TMJ-evoked Fos-LI was similar in males and females; however, significant differences in cell counts were seen for FG single-labeled and Fos/FG double-labeled neurons in trigeminal brainstem. After vlPAG injections, the number of FG-labeled neurons in trigeminal subnucleus interpolaris (Vi), ventral interpolaris/caudalis transition (vl-Vi/Vc), and dorsal paratrigeminal region (dPa5) was greater in females than males. The percentage of Fos/FG double-labeled neurons in vl-Vi/Vc and dPa5 after vlPAG injection also was greater in females than males. In contrast, after Po injections, males displayed a greater number of FG-labeled neurons in superficial laminae (Lam I/II) of trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C(1-2)) and deeper laminae (Lam III/V) at C(1-2) than females. The percentage of Fos/FG double-labeled neurons in Lam I/II of Vc after Po injection also was greater in males than females. These data revealed significant sex differences in ascending projections from TMJ-responsive neurons in trigeminal brainstem. Such differences may influence the ability of males and females to recruit autonomic reflexes and endogenous pain control circuits relevant for TMJ nociception.
    Neuroscience 11/2011; 203:230-43. DOI:10.1016/j.neuroscience.2011.11.042 · 3.36 Impact Factor

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  • 2008-2015
    • University of Minnesota Twin Cities
      • Department of Diagnostic and Biological Sciences
      Minneapolis, Minnesota, United States
  • 2009-2014
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
  • 1987-2007
    • Rhode Island Hospital
      Providence, Rhode Island, United States
    • Providence College
      Providence, Rhode Island, United States
  • 1990-2000
    • Brown University
      • • Department of Surgery
      • • Division of Biology and Medicine
      Providence, Rhode Island, United States