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Temporal Aspects Of Endogenous Pain Modulation During A Noxious Stimulus Prolonged For 1 Day, Marie K. Hoeger Bement, Kristian K. Petersen, Line B. Sørensen, Hjalte H. Andersen, Thomas Graven-Nielsen

Physical Therapy Faculty Research and Publications

Background

This study investigated (a) if a prolonged noxious stimulus (24‐hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and (b) if acute pain relief or exacerbation (cooling and heating the capsaicin patch) during the prolonged noxious stimulus would affect central pain modulation.

Methods

Twenty‐eight participants (26.2 ± 1.0 years; 12 women) wore a transdermal 8% capsaicin patch on the forearm for 24 hr. Data were collected at baseline (Day 0), 1 hr, 3 hr, Day 1 (post‐capsaicin …

Evaluation Of Vascular Control Mechanisms Utilizing Video Microscopy Of Isolated Resistance Arteries Of Rats, Kathleen M. Lukaszewicz, Matthew J. Durand, Jessica R. C. Priestley, James R. Schmidt, L. Adrienne Allen, Aron M. Geurts, Julian H. Lombard

Physical Therapy Faculty Research and Publications

This protocol describes the use of in vitro television microscopy to evaluate vascular function in isolated cerebral resistance arteries (and other vessels), and describes techniques for evaluating tissue perfusion using Laser Doppler Flowmetry (LDF) and microvessel density utilizing fluorescently labeled Griffonia simplicifolia (GS1) lectin. Current methods for studying isolated resistance arteries at transmural pressures encountered in vivo and in the absence of parenchymal cell influences provide a critical link between in vivo studies and information gained from molecular reductionist approaches that provide limited insight into integrative responses at the whole animal level. LDF and techniques to selectively identify arterioles and …

Ventilation And Neurochemical Changes During Μ-Opioid Receptor Activation Or Blockade Of Excitatory Receptors In The Hypoglossal Motor Nucleus Of Goats, Thomas M. Langer, Suzanne E. Neumueller, Emma Crumley, Nicholas J. Burgraff, Sawan Talwar, Matthew R. Hodges, Lawrence Pan, Hubert V. Forster

Physical Therapy Faculty Research and Publications

Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally (n = 5) or bilaterally (n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala², N-MePhe⁴, Gly-ol]enkephalin (DAMGO; 100 µM) decreased …

Effects On Breathing Of Agonists To Μ-Opioid Or GabaA Receptors Dialyzed Into The Ventral Respiratory Column Of Awake And Sleeping Goats, Thomas M. Langer Iii, Suzanne E. Neumueller, Emma Crumley, Nicholas J. Burgraff, Sawan Talwar, Matthew R. Hodges, Lawrence Pan, Hubert V. Forster

Physical Therapy Faculty Research and Publications

Pulmonary ventilation (V̇_I) in awake and sleeping goats does not change when antagonists to several excitatory G protein-coupled receptors are dialyzed unilaterally into the ventral respiratory column (VRC). Concomitant changes in excitatory neuromodulators in the effluent mock cerebral spinal fluid (mCSF) suggest neuromodulatory compensation. Herein, we studied neuromodulatory compensation during dialysis of agonists to inhibitory G protein-coupled or ionotropic receptors into the VRC. Microtubules were implanted into the VRC of goats for dialysis of mCSF mixed with agonists to either μ-opioid (DAMGO) or GABA_A (muscimol) receptors. We found: (1) V̇_I decreased during unilateral but increased during …

State-Dependent And -Independent Effects Of Dialyzing Excitatory Neuromodulator Receptor Antagonists Into The Ventral Respiratory Column, Thomas M. Langer Iii, Suzanne E. Neumueller, Emma Crumley, Nicholas J. Burgraff, Sawan Talwar, Matthew R. Hodges, Lawrence Pan, Hubert V. Forster

Physical Therapy Faculty Research and Publications

Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-Bötzinger complex region] of awake goats increased pulmonary ventilation (V̇i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V̇i or f, but increases local SP. Herein, we tested hypotheses that 1) local compensatory 5-HT and SP responses to 50 mM atropine …

Combined Unilateral Blockade Of Cholinergic, Peptidergic, And Serotonergic Receptors In The Ventral Respiratory Column Does Not Affect Breathing In Awake Or Sleeping Goats, Clarissa Muere, Suzanne Neumueller, Samantha Olesiak, Justin Robert Miller, Thomas Langer, Matthew Hodges, Lawrence Pan, Hubert Forster

Physical Therapy Faculty Research and Publications

Previous work in intact awake and sleeping goats has found that unilateral blockade of excitatory inputs in the ventral respiratory column (VRC) elicits changes in the concentrations of multiple neurochemicals, including serotonin (5-HT), substance P, glycine, and GABA, while increasing or having no effect on breathing. These findings are consistent with the concept of interdependence between neuromodulators, whereby attenuation of one modulator elicits compensatory changes in other modulators to maintain breathing. Because there is a large degree of redundancy and multiplicity of excitatory inputs to the VRC, we herein tested the hypothesis that combined unilateral blockade of muscarinic acetylcholine (mACh), …

Blockade Of Neurokinin-1 Receptors In The Ventral Respiratory Column Does Not Affect Breathing But Alters Neurochemical Release, Clarissa Muere, Suzanne Neumueller, Samantha Olesiak, Justin Miller, Matthew Hodges, Lawrence Pan, Hubert Forster

Physical Therapy Faculty Research and Publications

Substance P (SP) and its receptor, neurokinin-1 (NK1R), have been shown to be excitatory modulators of respiratory frequency and to stabilize breathing regularity. Studies in anesthetized mice suggest that tonic activation of NK1Rs is particularly important when other excitatory inputs to the pre-Bötzinger complex in the ventral respiratory column (VRC) are attenuated. Consistent with these findings, muscarinic receptor blockade in the VRC of intact goats elicits an increase in breathing frequency associated with increases in SP and serotonin concentrations, suggesting an involvement of these substances in neuromodulator compensation. To gain insight on the contribution to breathing of endogenous SP and …

Evidence For Respiratory Neuromodulator Interdependence After Cholinergic Disruption In The Ventral Respiratory Column, Clarissa Muere, Suzanne Neumueller, Justin Robert Miller, Samantha Olesiak, Matthew Hodges, Lawrence Pan, Hubert Forster

Physical Therapy Faculty Research and Publications

Reverse dialysis of the muscarinic receptor antagonist, atropine (ATR, 50 mM), into the pre-Bötzinger Complex region of the ventral respiratory column (VRC) of awake and sleeping goats increases breathing frequency and serotonin (5-HT), substance P (SP), glycine, and GABA concentrations in the effluent dialysate. Herein, we report data from goats in which we reverse dialyzed 5 mM ATR or specific antagonists of M2 or M3 muscarinic receptors into the VRC. The effects on frequency of all three antagonists were not significantly different from time control studies. 5 mM ATR and the M3 antagonist increased SP sevenfold less than 50 mM …

Changes In Glutamate Receptor Subunits Within The Medulla In Goats After Section Of The Carotid Sinus Nerves, Justin Robert Miller, Suzanne Neumueller, Clarissa Muere, Samantha Olesiak, Lawrence Pan, John D. Bukowy, Asem O. Daghistany, Matthew Hodges, Hubert Forster

Physical Therapy Faculty Research and Publications

The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO₂ chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each …

Contributions Of The Kölliker-Fuse Nucleus To Coordination Of Breathing And Swallowing, Joshua M. Bonis, Suzanne E. Neumueller, K. L. Krause, Lawrence Pan, Matthew R. Hodges, Hubert V. Forster

Physical Therapy Faculty Research and Publications

Herein we compare the effects of perturbations in the Kölliker–Fuse nucleus (KFN) and the lateral (LPBN) and medial (MPBN) parabrachial nuclei on the coordination of breathing and swallowing. Cannula was chronically implanted in goats through which ibotenic acid (IA) was injected while awake. Swallows in late expiration (E) always reset while swallows in early inspiration (I) never reset the respiratory rhythm. Before cannula implantation, all other E and I swallows did not reset the respiratory rhythm, and had small effects on E and I duration and tidal volume (V_T). However, after cannula implantation in the MPBN and …

The Effects Of Lesions In The Dorsolateral Pons On The Coordination Of Swallowing And Breathing In Awake Goats, Joshua M. Bonis, S. E. Neumueller, B. D. Marshall, K. L. Krause, B. Qian, Lawrence Pan, M. R. Hodges, Hubert V. Forster

Physical Therapy Faculty Research and Publications

The purpose of this retrospective study was to gain insight into the contribution of the dorsolateral pons to the coordination of swallowing and breathing in awake goats. In 4 goats, cannulas were chronically implanted bilaterally through the lateral (LPBN) and medial (MPBN) parabrachial nuclei just dorsal to the Kölliker–Fuse nucleus (KFN). After >2 weeks recovery from this surgery, the goats were studied for 5½ h on a control day, and on separate days after receiving 1 and 10 μl injections of ibotenic acid (IA) separated by 1 week. The frequency of swallows did not change during the control and 1 …

Site-Specific Effects On Respiratory Rhythm And Pattern Of Ibotenic Acid Injections In The Pontine Respiratory Group Of Goats, Joshua M. Bonis, Suzanne Neumueller, Katie L. Krause, T. Kiner, A. Smith, B. D. Marshall, B. Qian, Lawrence Pan, Hubert Forster

Physical Therapy Faculty Research and Publications

To probe further the contributions of the rostral pons to eupneic respiratory rhythm and pattern, we tested the hypothesis that ibotenic acid (IA) injections in the pontine respiratory group (PRG) would disrupt eupneic respiratory rhythm and pattern in a site- and state-specific manner. In 15 goats, cannulas were bilaterally implanted into the rostral pontine tegmental nuclei (RPTN; n = 3), the lateral (LPBN; n = 4) or medial parabrachial nuclei (MPBN; n = 4), or the Kölliker-Fuse nucleus (KFN; n = 4). After recovery from surgery, 1- and 10-μl injections (1 wk apart) of IA were made bilaterally through the …

The Pontine Respiratory Group, Particularly The Kölliker-Fuse Nucleus, Mediates Phases Of The Hypoxic Ventilatory Response In Unanesthetized Goats, Joshua M. Bonis, Suzanne E. Neumueller, K. L. Krause, T. Kiner, A. Smith, B. D. Marshall, B. Qian, Lawrence Pan, Hubert V. Forster

Physical Therapy Faculty Research and Publications

The objective of the present study was to test the hypothesis that, in the in vivo awake goat model, perturbation/lesion in the pontine respiratory group (PRG) would decrease the sensitivity to hypercapnia and hypoxia. The study reported herein was part of two larger studies in which cholinergic modulation in the PRG was attenuated by microdialysis of atropine and subsequently ibotenic acid injections neurotoxically lesioned the PRG. In 14 goats, cannula were bilaterally implanted into either the lateral (n = 4) or medial (n = 4) parabrachial nuclei or the Kölliker-Fuse nucleus (KFN, n = 6). Before and after …

Μ-Opioid Receptor Agonist Injections Into The Presumed Pre-Bötzinger Complex And The Surrounding Region Of Awake Goats Do Not Alter Eupneic Breathing, K. L. Krause, Suzanne E. Neumueller, B. D. Marshall, T. Kiner, Joshua M. Bonis, Lawrence Pan, B. Qian, Hubert V. Forster

Physical Therapy Faculty Research and Publications

Opioids are clinically important in the alleviation of pain. An undesirable side effect of opioids is depression of breathing. Data from isolated preparations suggest this effect is due to attenuation of discharge activity of neurons in the pre-Bötzinger complex (preBötzC), a medullary area with respiratory rhythmogenic properties. The purpose of this study was to examine how [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), a μ-opioid receptor agonist, affected breathing after injection into the presumed preBötzC of the adult awake goat. We hypothesized that DAMGO would cause breathing to decrease and become irregular when injected into the presumed preBötzC and the surrounding region of the conscious …

Normal Breathing Pattern And Arterial Blood Gases In Awake And Sleeping Goats After Near Total Destruction Of The Presumed Pre-Bötzinger Complex And The Surrounding Region, Katie L. Krause, Hubert Forster, T. Kiner, S. E. Davis, Joshua M. Bonis, B. Qian, Lawrence Pan

Physical Therapy Faculty Research and Publications

Abrupt neurotoxic destruction of >70% of the pre-Bötzinger complex (preBötzC) in awake goats results in respiratory and cardiac failure (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV. J Appl Physiol 97: 1629–1636, 2004). However, in reduced preparations, rhythmic respiratory activity has been found in other areas of the brain stem (Huang Q, St. John WM. J Appl Physiol 64: 1405–1411, 1988; Janczewski WA, Feldman JL. J Physiol 570: 407–420, 2006; Lieske SP, Thoby-Brisson M, Telgkamo P, Ramierz JM. Nature Neurosci 3: 600–607, 2000; St. John WM, Bledsoe TA. J Appl …

The Cerebellar Fastigial Nucleus Contributes To Co2-H+ Ventilatory Sensitivity In Awake Goats, P. F. Martino, S. Davis, C. Opansky, Katie L. Krause, Joshua M. Bonis, Lawrence Pan, B. Qian, Hubert V. Forster

Physical Therapy Faculty Research and Publications

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO₂-H⁺ sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N = 9) for injection (0.5–10 μl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO₂-H⁺ sensitivity did not differ significantly (P > 0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic Pa_CO2 (P > 0.10). The coefficient of variation of …

In Vitro Effects Of Two Silver Electrodes On Select Wound Pathogens, Linda Jean Laatsch-Lybeck, Poh Chye Ong, Luther C. Kloth

Physical Therapy Faculty Research and Publications

The use of electrical current to promote wound healing is well documented. However, little is understood about the effects of micro-amperage direct current (μADC) on growth of wound pathogens. The purpose of this project was to investigate the antibacterial effects of a silver wire/silver nylon electrode carrying μADC in vitro on several Gram positive and Gram negative bacteria. The current was delivered via silver wire and silver nylon electrodes at an amplitude of 100 μA for a 30-minute duration in an in vitro system. Results demonstrated that only silver wire carrying current inhibited bacterial growth around …