Injection Of Hypertonic Saline Research Articles

Experimental cervical interspinous ligament pain altered cervical joint motion during dynamic extension movement

BackgroundAlthough the cervical interspinous ligament is a potential source of neck pain, the effects on cervical joint motion and pressure pain sensitivity has never been investigated. The understanding of the relationship will broaden our understanding of cervical biomechanics and improve diagnosis and treatment of neck pain. MethodsFluoroscopy videos of cervical flexion and extension movements and pressure pain thresholds over bilateral C2/C3 and C5/C6 facet joints were collected in fifteen healthy subjects before and after injections of hypertonic and isotonic saline in C4/C5 ISL. The videos were divided into 10 even epochs and the motion of individual joints during each epoch was extracted. Joint motion parameters including anti-directional motion, pro-directional motion, total joint motion and joint motion variability were extracted across epochs. Joint motion parameters and PPTs were compared before and after injection of hypertonic and isotonic saline separately. FindingsCompared with baselines: hypertonic saline injection 1) decreased anti-directional motion and joint motion variability at C4/C5 (P < 0.05) and increased at C2/C3 (P < 0.05) during extension; 2) increased total joint motion of C0/C1 during first half range (P < 0.05) and decreased during second half range of extension, and total joint motion of C2/C3 increased during second half range of extension (P < 0.05) and; 3) increased pressure pain thresholds over left C2/C3 facet joint (P < 0.01). InterpretationThe cervical interspinous ligament pain redistributed anti-directional motion between C4/C5 and C2/C3 during dynamic extension and decreased pressure pain sensitivity over the left C2/C3 facet joint.

Interhemispheric Inhibition Is Reduced in Response to Acute Muscle Pain: A Cross-Sectional Study Using Transcranial Magnetic Stimulation

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Evidence suggests a reduction in interhemispheric inhibition (IHI) from the “affected” (contralateral to the side of pain) to the “unaffected” primary motor cortex (M1) could contribute. However, the effect of short-lasting acute muscle pain on IHI, and whether any changes are related to early sensorimotor changes in the unaffected limb, is unknown. Using a cross-sectional study design, IHI was investigated in 20 healthy individuals before, immediately after, and 30 minutes after the induction of acute muscle pain in the right first dorsal interosseous muscle via a bolus injection of hypertonic saline. Transcranial magnetic stimulation was used to assess corticomotor excitability and short and long latency IHI. Pain intensity and quality were recorded using an 11-point numerical rating scale and the McGill Pain Questionnaire. Pressure pain thresholds were assessed in the affected and unaffected first dorsal interosseous and both tibialis anterior muscles. Participants reported an average pain intensity of 4.8 points (standard deviation = 1.3 points). Compared with baseline, corticomotor excitability was decreased at all time points in the affected but not the unaffected M1. IHI was decreased at all time points from the affected to the unaffected M1. Pressure pain thresholds were decreased over both first dorsal interosseous muscles at 30 minutes of follow-up. These findings suggest a decrease in IHI from the affected to the unaffected M1 that occurs rapidly after the onset of acute pain and could contribute to the development of bilateral symptoms. PerspectiveThe affected M1 (contralateral to the side of pain) releases inhibition over the unaffected M1 within minutes after the onset of acute muscle pain. This finding could have relevance for the development of bilateral sensorimotor symptoms in unilateral pain conditions.

Conditioned hedonic responses elicited by contextual cues paired with nausea or with internal pain.

Pairing a taste with either internal pain or nausea, despite equivalent effects on voluntary consumption, has dissociable effects on hedonic responses: Only pairing with nausea results in the production of disgust reactions, while pairing with internal pain results in conditioned fear as indicated by immobility. Here, we use orofacial reactions to examine the hedonic responses elicited by contextual, nonflavor, cues paired with nausea produced by injection of lithium chloride (LiCl) or internal pain caused by injection of hypertonic saline. In Experiment 1, aversive orofacial responses were the specific context-elicited behaviors in the rats injected with LiCl, whereas immobility was seen in the animals injected with hypertonic saline. In Experiment 2, rats first received discriminative training with two contexts, where one context was paired with LiCl or hypertonic saline, and the other context with isotonic saline. After this, rats were intraorally infused with a flavor (conditioned stimulus (CS) +) in the paired context, and with a different flavor (CS-) in the unpaired context. Second-order conditioning was then examined in a test conducted in the unpaired context. The infusion of the CS + flavor produced aversive orofacial responses in the rats injected with LiCl but immobility in the subjects injected with hypertonic saline. The results suggest that nonflavor cues support conditioned hedonic responses in the same way as flavor cues, which implies that the quality of aversion learning (conditioned nausea vs. fear) is primarily determined by the nature of the aversive event and not the type of conditioned cue. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Review of rodent hypertensive glaucoma models.

Glaucoma is a neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is a primary risk factor for the development and progression of glaucoma. Rodent models of glaucoma have greatly improved our understanding of the pathophysiology of glaucoma and served as a useful tool to investigate neuroprotective agents. An ideal glaucoma animal model should be easy to induce, reproducible, biologically plausible and predictable. Of the available animal models of glaucoma, rodents are commonly studied because they have a relatively short life span and can be genetically altered. A successful hypertensive glaucoma model should induce structural glaucomatous changes: including loss of retinal nerve fibres, retinal ganglion cells and optic-disc cupping along with IOP elevation. The level and duration of IOP elevation should be titratable depending on the targeted glaucomatous damage. This review summarizes the outcomes of induced rodent hypertensive glaucoma models including intracameral injection of microbeads, laser photocoagulation, episcleral vein cauterization, injection of hypertonic saline and hyaluronic acid. We aim to provide a detailed overview of each of the models with a focus on parameters that defines a successful glaucoma model. The induced IOP elevation and duration of elevation varied among the different models and strain of rodent; nonetheless, they all achieved a sustainable raised IOP with corresponding RGC loss. The limitations of each model are discussed.

Perflubron Distribution During Transition From Gas to Total Liquid Ventilation.

Total liquid ventilation (TLV) using perfluorocarbons has shown promising results for the management of neonatal respiratory distress. However, one important safety consideration for TLV is a better understanding of the early events during the transition to TLV, especially regarding the fate of residual air in the non-dependent-lung regions. Our objective was to assess perflubron distribution during transition to TLV using electrical impedance tomography, complemented by fluoroscopy, in a neonatal lamb model of induced surfactant deficiency. Eight lambs were anesthetized and ventilated in supine position. Surfactant deficit was induced by saline lung lavage. After deflation, lungs were filled with 25 ml/kg perflubron over 18 s, and TLV was initiated. Electrical impedance tomography data was recorded from electrodes placed around the chest, during the first 10 and at 120 min of TLV. Lung perfusion was also assessed using hypertonic saline injection during apnea. In addition, fluoroscopic sequences were recorded during initial lung filling with perfluorocarbons, then at 10 and 60 min of TLV. Twelve lambs were used as controls for histological comparisons. Transition to TLV involved a short period of increased total lung volume (p = 0.01) secondary to recruitment of the dependent lung regions. Histological analysis shows that TLV was protective of these same regions when compared to gas-ventilated lambs (p = 0.03). The non-dependent lung regions filled with perflubron over at least 10 min, without showing signs of overdistention. Tidal volume distribution was more homogenous in TLV than during the preceding gas ventilation. Perflubron filling was associated with a non-significant increase in the anterior distribution of the blood perfusion signal, from 46 ± 17% to 53 ± 6% (p = 0.4). However, combined to the effects on ventilation, TLV had an instantaneous effect on ventilation-perfusion relationship (p = 0.03), suggesting better coupling. Conclusion: transition to TLV requires at least 10 min, and involves air evacuation or dissolution in perflubron, dependent lung recruitment and rapid ventilation-perfusion coupling modifications. During that time interval, the total lung volume transiently increases. Considering the potential deleterious effect of high lung volumes, one must manage this transition phase with care and, we suggest using a real-time monitoring system such as electrical impedance tomography.

Experimental Pain Decreases Corticomuscular Coherence in a Force- But Not a Position-Control Task

Differences in neural drive could explain variation in adaptation to acute pain between postural and voluntary motor actions. We investigated whether cortical contributions, quantified by corticomuscular coherence, are affected differently by acute experimental pain in more posturally focused position-control tasks and voluntary focused force-control tasks. Seventeen participants performed position- and force-control contractions with matched loads (10% maximum voluntary contraction) before and during pain (injection of hypertonic saline into the infrapatellar fat pad of the knee). Surface electromyography (EMG) of right knee extensor and flexor muscles was recorded. Electroencephalography (EEG) was recorded using a 128-channel sensor net. Corticomuscular coherence was calculated between 4 EEG electrodes that approximated the contralateral motor cortical area, and EMG. Coherence, EEG, EMG, and target performance accuracy were compared between task types and pain states. Before pain, coherence EEG and EMG did not differ between tasks. During pain, EMG increased in both tasks, but the force-control task showed greater pain interference (decreased coherence, higher EEG frequencies, and increased force fluctuations). Neural substrates of motor performance of postural functions are changed uniquely by experimental pain, which might be explained by differences in cortical demands. Our results provide new insights into the mechanisms of motor adaptations during acute pain. PerspectiveUnderstanding of the mechanisms underlying adaptations to motor function in acute pain is incomplete. Experimental work almost exclusively focuses on voluntary motor actions, but these adaptations may be inappropriate for postural actions. Our results show less pain-related interference in brain activity and its relationship to muscle activation during position-control tasks.

An Intraplantar Hypertonic Saline Assay in Mice for Rapid Screening of Analgesics.

Development of new analgesics is limited by shortcomings of existing preclinical screening assays such as wide variations in response, suitability for a narrow range of analgesics, and propensity to induce tissue damage. Our aim was to determine the feasibility of a new in vivo animal assay as an analgesic screen based on nociceptive responses (licking and biting) after intraplantar (i.pl.) injection of hypertonic saline (HS) in mice. With approval from the Institutional Animal Care Committee, we conducted a randomized, investigator-blinded in vivo study in adult CD-1 mice. We first studied the concentration-response relationship, time course, and sex difference of animals' nociceptive responses to HS. Subsequently, we assessed the screening ability of the HS assay to detect a range of established analgesics belonging to different classes. Finally, we performed histopathologic studies to assess potential tissue damage. The response produced by i.pl. HS was greater and longer in female than in male mice. The responses to HS were concentration dependent with minimal variance. Ten percent HS evoked a maximal response within the first 5 minutes. Morphine dose-dependently attenuated animals' nociceptive responses (1-10 mg/kg intraperitoneally [i.p.]). The peripherally restricted µ-opioid receptor agonist, loperamide, reduced nociceptive responses when injected locally (30-100 µg/paw, i.pl.) but not systemically (1-10 mg/kg, i.p.). Acetylsalicylic acid (300 mg/kg, i.p.), naproxen (150 mg/kg, i.p), and acetaminophen (300 mg/kg, i.p.) all decreased nociceptive responses, as did i.pl. coinjections of lidocaine (0.003%-1%) with 10% HS. Histopathologic assessment revealed no tissue damage due to HS. The i.pl. HS assay is easily performed, rapidly detects standard analgesics, and produces minimal animal suffering without tissue damage. We propose this assay as a useful addition to the armamentarium of existing preclinical analgesic screens.

Impact of medial versus lateral knee pain on deep tissue hyperalgesia and muscle strength.

Accumulating evidence indicates that knee pain gives rise to sensory and motor alterations, however, whether different profile of knee pain causes different alterations has not been investigated. The purpose of this experimental study is to clarify characteristics of medial and lateral knee pain and its potential for modulating sensory and motor function in humans. Fourteen healthy men were included. Medial knee pain (MP) was induced by injection of hypertonic saline (0.5mL) into the tibial insertion of the medial collateral ligament. For comparison, lateral knee pain (LP) was induced by injection of hypertonic saline identically into the iliotibial tract. Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a continuous electronic visual analogue scale (VAS). Before, during and after the painful state, pressure pain thresholds from the knee (PPTs), maximal isometric muscle strength of the quadriceps and grip power were assessed bilaterally. MP demonstrated significantly higher VAS scores than LP and compared with control. PPTs decreased on medial and lateral knee in MP but only on the lateral knee in LP. Quadriceps muscle strength and grip power reduced bilaterally in both models, however, MP caused significantly greater reduction of ipsilateral quadriceps strength compared with LP. Medial knee pain has a greater impact on deep tissue hyperalgesia and reduction of the muscle strength compared with lateral knee pain. This is a novel finding that should be taken into consideration in a treatment strategy for painful knee patients. The experimental medial knee pain model demonstrated higher pain intensity, more localized pain distribution, widespread deep tissue hyperalgesia and more severe inhibition of muscle strength compared with the lateral knee pain model.

Angiotensin 1–7 Action in the Lateral Preoptic Area is Involved in Urinary Bladder Regulation in Female Wistar Rats.

BackgroundChemical lesions of the lateral preoptic area (LPA) enhance water intake induced by subcutaneous injection of hypertonic saline in rats. On the other hand, the LPA section abolishes the increase in intravesical pressure (IP) induced by olfactory tubercle stimulation in dogs. Immunohistochemical labeling has demonstrated the presence of Mas receptors for Angiotensin‐(1–7) in LPA. It is not known whether neurons with Mas receptors in LPA are involved in urinary bladder regulation.AimWe investigated the effects of activation or blockade of Mas receptors for angiotensin‐(1–7) in LPA on intravesical pressure in anesthetized female rats.Materials and methodsFemale Wistar rats (~240 g, N=6) underwent to a stereotaxic surgery for implantation of stainless steel guide cannulas into the LPA under ketamine and xylazin anesthesia. After 7 days, the animals were anesthetized and maintained with 2% isoflurane in 100% O2 and submitted to cannulation of the femoral artery and vein, placement of a miniaturized Doppler flow probe around the left renal artery to measure the renal blood flow and cannulation of the urinary bladder for IP measurements. After baseline IP and cardiovascular parameters recordings for 15 min, angiotensin‐(1–7) (5 nmol/ uL) or saline (1 uL) or A‐779 (Mas receptor antagonist, 50 nmol/uL) was injected into the LPA and the variables were measured for additional 60 min.ResultsUnilateral injection of angiotensin‐(1–7) into LPA evoked a significant increase in IP (187.5±37.2%) compared to saline (−2.1±1.9%). Unilateral injection of A‐779 into LPA decreased the IP (−15.9±2.8%) in comparison to saline (2.0±1.1%). Interestingly, the decrease in IP was enhanced after bilateral injection of A‐779 into LPA (−27.3±3.4%) compared to the unilateral injection of this drug and also in comparison to saline (−2.9±1.6%) bilaterally into LPA. No significant changes in cardiovascular parameters after angiotensin‐(1–7) or saline or A‐779 in APL were observed.ConclusionThe data suggest that LPA is an important part of the circuit that regulates the urinary bladder activity mediated by angiotensin‐(1–7).Support or Funding InformationFinancial support: FAPESP and NEPAS‐FMABCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Light Touch Contact Improves Pain-Evoked Postural Instability During Quiet Standing

To investigate if attention to additional sensory information from the fingertip can improve postural stability during pain, which is known to impair balance. In 16 healthy volunteers, experimental pain was induced by intramuscular injection of hypertonic saline in the right vastus medialis muscle (isotonic saline used as nonpainful control, intramuscular injection in the same location). Pain intensity was assessed on an 11-point numeric rating scale (NRS; 0 representing "no pain" and 10 "maximum pain"). Subjects were asked to stand as still as possible on a force plate for 40 seconds with their eyes closed. Their postural stability was quantified by the area and velocity of center of pressure (CoP) displacement. The CoP was recorded with and without pain during two different conditions: 1) no touch and 2) the subjects were asked to lightly touch a curtain with their right index finger and focus their attention on keeping it as still as possible. Hypertonic injections induced higher NRS scores compared with control injections (P < 0.05). During the hypertonic injection condition, the CoP area and velocity in both directions increased during no touch compared with the light touch condition (P < 0.05). No differences were found during light touch between the hypertonic and isotonic injection conditions. Although experimental knee-related pain impaired postural stability, lightly touching a curtain with the fingertip decreased postural sway during painful conditions. Providing additional sensory information while pain patients are performing balance exercises may improve postural stability and increase the quality of exercise, consequent rehabilitation protocols, and clinical outcomes.

Hypertonic Saline Injection Model of Experimental Glaucoma in Rats.

A reliable method of creating chronic elevation of intraocular pressure (IOP) in rodents is an important tool in reproducing and studying the mechanisms of optic nerve injury that occur in glaucoma. In addition, such a model could provide a valuable method for testing potential neuroprotective treatments. This paper outlines the basic methods for producing obstruction of aqueous humor outflow and IOP elevation by injecting hypertonic saline (a sclerosant) into the aqueous outflow pathway. This is one of several rodent glaucoma models in use today. In this method, a plastic ring is placed around the equator of the eye to restrict injected saline to the limbus. By inserting a small glass microneedle in an aqueous outflow vein in the episclera and injecting hypertonic saline toward the limbus, the saline is forced into Schlemm's canal and across the trabecular meshwork. The resultant inflammation and scarring of the anterior chamber angle occurs gradually, resulting in a rise in IOP after approximately 1 week. This article will describe the equipment necessary for producing this model and the steps of the technique itself.

Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake

Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, OxtrPBN neurons were activated by fluid satiation and hypertonic saline injection. OxtrPBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (OxtPVH neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated OxtrPBN neurons. Our results suggest that OxtrPBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

Running-based pica and taste avoidance in rats.

Running in an activity wheel generates pica behavior (kaolin clay intake) in rats. Wheel running also results in Pavlovian conditioned avoidance of the taste solution consumed immediately before the running. Since pica has been considered a behavioral marker of nausea in rats, these findings suggest that wheel running induces nausea, which is the underlying physiological state for establishing taste avoidance. This article reports a replication of running-based pica in rats (Experiment 1) and concurrent demonstrations of running-based pica and taste avoidance in the same animals (Experiments 2 and 3). Also shown is that pica does not alleviate running-based taste avoidance (Experiment 3). Another finding is that pica is generated by a nausea-inducing lithium chloride injection but not by a pain-inducing hypertonic saline injection (Experiment 4). These results, when taken together, support the hypothesis that pica behavior generated by wheel running reflects nausea in rats.

Muscle Pain Induces a Shift of the Spatial Distribution of Upper Trapezius Muscle Activity During a Repetitive Task: A Mechanism for Perpetuation of Pain With Repetitive Activity?

An association exists between repetitive movements and the development or perpetuation of neck-shoulder muscle pain. The mechanisms underlying this association remain unclear. This observational study investigated the effect of upper trapezius muscle pain on the distribution of upper trapezius activity during repetitive lifting. It was hypothesized that nociception would change the distribution of activity resulting in activation of muscle regions which would not normally be active during the task. Healthy men repeatedly lifted a box with a cycle time of 3 seconds for 50 cycles, at baseline, following injection of isotonic and hypertonic saline into the upper trapezius muscle and 15 minutes after the last injection. High-density surface electromyography (EMG) was recorded from the upper trapezius using a grid of 64 electrodes. The EMG amplitude was computed for each location to form a map of the EMG amplitude distribution. During the painful condition, the overall EMG amplitude was lower compared with all other conditions (P<0.05) and in addition, the center of upper trapezius activity was shifted toward the caudal region of the muscle (P<0.01), a region not normally active during the task. The described alterations of muscle activity likely play an important role in the perpetuation of pain during repetitive activity. Novel mapping of the spatial distribution of upper trapezius muscle activity showed that nociception induced a redistribution of activity during repetitive lifting. This knowledge provides new insights into the mechanisms underlying the perpetuation of pain with repetitive activity.

Dose-dependent mortality involving convulsions due to subarachnoid Urografin® injection in rats.

An ionically hypertonic contrast medium Urografin® was inadvertently administered into the subarachnoid space of an individual and this resulted in convulsions and acute respiratory failure. We examined the effects of subarachnoid Urografin® injections on the rat central nervous system. The onset and frequency of the convulsions, as well as fatality, were dependent on the amount of Urografin® administered. No convulsions were observed in rats receiving injections of hypertonic NaCl solution or saline. The results confirmed that subarachnoid injections of Urografin® cause convulsions and death, as previously reported in human cases, and our study ascertained the causal relationship between the above malpractice and fatal outcomes.

Facilitatory and inhibitory pain mechanisms are altered in patients with carpal tunnel syndrome.

Preliminary evidence from studies using quantitative sensory testing suggests the presence of central mechanisms in patients with carpal tunnel syndrome (CTS) as apparent by widespread hyperalgesia. Hallmarks of central mechanisms after nerve injuries include nociceptive facilitation and reduced endogenous pain inhibition. Methods to study nociceptive facilitation in CTS so far have been limited to quantitative sensory testing and the integrity of endogenous inhibition remains unexamined. The aim of this study was therefore to investigate changes in facilitatory and inhibitory processing in patients with CTS by studying hypersensitivity following experimentally induced pain (facilitatory mechanisms) and the efficacy of conditioned pain modulation (CPM, inhibitory mechanisms). Twenty-five patients with mild to moderate CTS and 25 age and sex matched control participants without CTS were recruited. Increased pain facilitation was evaluated via injection of hypertonic saline into the upper trapezius. Altered pain inhibition through CPM was investigated through cold water immersion of the foot as the conditioning stimulus and pressure pain threshold over the thenar and hypothenar eminence bilaterally as the test stimulus. The results demonstrated that patients with CTS showed a greater duration (p = 0.047), intensity (p = 0.044) and area (p = 0.012) of pain in response to experimentally induced pain in the upper trapezius and impaired CPM compared to the control participants (p = 0.006). Although typically considered to be driven by peripheral mechanisms, these findings indicate that CTS demonstrates characteristics of altered central processing with increased pain facilitation and reduced endogenous pain inhibition.

Hypertonic NaCl versus osmotic stimuli: distinct OVLT neurones can sense the difference to control sympathetic outflow and blood pressure.

Despite large fluctuations in salt and water intake, mammals are able to maintain electrolyte concentrations, particularly sodium (Na+) as the major determinant of osmolality of the extracellular fluid (ECF), within narrow physiological limits (∼300 mOsm kg−1). The two distinct sensory systems monitoring Na+ concentration and osmolality in the hypothalamic area of the brain are located outside the blood–brain barrier and are therefore known as circumventricular organs (CVOs). The osmosensitive neurones of CVOs are located in the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT). Direct projections from these areas to hypothalamic nuclei containing neurosecretory magnocellular neurones promote the release of water-conserving hormones such as arginine vasopressin (McKinley et al. 2001). Interestingly, these neurones also project to smaller parvocellular neurones located within other brain structures, such as the paraventricular nucleus of the hypothalamus (PVN) that modulate sympathetic nerve activity (SNA), an important mechanism in blood pressure (BP) homeostasis. The distinct physiological responses to maintain fluid balance triggered by infusion of hypertonic sodium chloride (NaCl) and equi-osmolar solutions have been debated for decades. McKinley and colleagues (1978) have shown that a peripheral osmoreceptor mechanism was most likely to be responsible for the thirst and antidiuresis induced by intracarotid infusion of hypertonic NaCl or sucrose in sheep. However, they also found support for a periventricular Na+ receptor mechanism because of differential drinking responses to intracerebroventricular (i.c.v.) administration of hypertonic NaCl or sucrose. The SFO seems to be the primary locus of NaCl sensing for the control of salt-intake behaviour at the central level, identified as a sensory mechanism that relies on activation of a Na+ channel (Nax); it is not osmosensing (Hyiama et al. 2004). The SFO is also involved in mediating the central Na+-induced pressor response, since administration of NaCl-rich artificial cerebrospinal fluid (aCSF) into the SFO caused an increase in BP, which was blunted by an angiotensin II type 1 (AT1) receptor antagonist at the same site. However, equi-osmotic infusion of manitol did not change BP, indicating that the pressor response is Na+ specific and not due to osmolality or volume effects (Tiruneh et al. 2013). Not only SFO, but also OVLT neurones are capable of detecting extracellular NaCl concentration and altering the sympathetic nerve discharge in order increase BP (Kinsman et al. 2017b). However, to date, no study has been able to show whether distinct cellular processes of osmosensitive neurones can differentiate between hyperosmolality versus hypertonic NaCl stimulus to selectively control SNA and BP. In this issue of The Journal of Physiology, Kinsman and co-workers (2017a) addressed this important issue by performing an elegant in vivo neurophysiological study. They determined how subsets of OVLT neurones respond differentially to hypertonic NaCl versus osmolality and subsequently regulate the sympathetic nervous system. More precisely, they showed that local injection of hypertonic saline into the OVLT produced an increase in SNA and BP, whereas an equi-osmotic stimulus of mannitol/sorbitol solutions had no effect. Moreover, these authors combined in vitro whole-cell recordings to demonstrate that stimulation with hypertonic saline caused the discharge frequency of OVLT neurones to increase, unlike stimulation with the equi-osmotic mannitol solution. These findings by Kinsman and colleagues (2017a) open several interesting perspectives for further investigation regarding the functional significance of distinct cellular responses of Na+ and osmosensitive OVLT neurones: (i) What are the physiological mechanisms, phenotype and neurotransmitters released by the functionally distinct OVLT neurones? (ii) How do these differences translate to hypertonic NaCl and osmotically driven sympathetic responses and BP control? (iii) Do salt-sensitive rats (e.g. Dahl-Salt) show alterations in OVLT neuronal populations that control hydroelectrolytic balance, sympathetic hyperactivity and hypertension in response to high salt diet? (iv) It would be interesting to determine the contribution of the SFO compared to the OVLT to the sympathetic responses to hypertonic saline and osmolality challenges. Understanding the characteristics of the CVO neurones relating to control of body fluid and cardiovascular homeostasis in response to distinct osmotic stimuli will require a range of techniques from anatomical, molecular, biochemical and pharmaco/opto-genetic tools, and this paper by Kinsman and co-workers (2017a) is a great kick-off in elucidating the complex hierarchy and mechanisms of the osmoregulatory signalling network at the CNS level. None declared. V.R.A. is supported by The National Council for Scientific and Technological Development (CNPq) Research Fellow, and The State of Sao Paulo Research Funding Agency (FAPESP) no. 2016-21991-3.

Modeling liver electrical conductivity during hypertonic injection.

Metastases in the liver frequently grow as scattered tumor nodules that neither can be removed by surgical resection nor focally ablated. Previously, we have proposed a novel technique based on irreversible electroporation that may be able to simultaneously treat all nodules in the liver while sparing healthy tissue. The proposed technique requires increasing the electrical conductivity of healthy liver by injecting a hypersaline solution through the portal vein. Aiming to assess the capability of increasing the global conductivity of the liver by means of hypersaline fluids, here, it is presented a mathematical model that estimates the NaCl distribution within the liver and the resulting conductivity change. The model fuses well-established compartmental pharmacokinetic models of the organ with saline injection models used for resuscitation treatments, and it considers changes in sinusoidal blood viscosity because of the hypertonicity of the solution. Here, it is also described a pilot experimental study in pigs in which different volumes of NaCl 20% (from 100 to 200mL) were injected through the portal vein at different flow rates (from 53 to 171 mL/minute). The in vivo conductivity results fit those obtained by the model, both quantitatively and qualitatively, being able to predict the maximum conductivity with a 14.6% average relative error. The maximum conductivity value was 0.44second/m, which corresponds to increasing 4 times the mean basal conductivity (0.11second/m). The results suggest that the presented model is well suited for predicting on liver conductivity changes during hypertonic saline injection.

P83: Heel height affects lower extremity joint moments during walking with OpenSim software

Laterally wedged insoles are one of the gait modifications potentially slowing down progression of medial knee osteoarthritis. Clinical studies have, however, found large individual differences in the biomechanical effect and an insufficient pain reduction. To clarify if and how pain mediates mechanical changes during gait the current study investigated how acute experimental knee pain changes the mechanical effect of laterally wedged insoles in healthy subjects during walking.3D gait analysis was carried out for twelve healthy individuals. The study followed a cross-over design and data were collected with both a neutral and a 10-degree laterally wedged insole with experimental pain induced by hypertonic and isotonic saline injections into the infrapatellar fat pad. Peak knee adduction moment was the primary outcome. A repeated ANOVA (analysis of variance) was used to evaluate the relationship between the factors wedge, condition and test number.Wedges significantly reduced peak knee adduction moment but experimental knee pain did only marginally affect its magnitude in either condition. While frontal plane mechanics were relatively unaffected by pain, the sagittal plane knee extension moment increased with laterally wedging (P = 0.008), whereas late knee flexion moment was reduced by experimental knee pain (P = 0.04).The effect of laterally wedged insoles in attenuating knee adduction moment during walking is independent of experimental knee pain. The present study provides evidence that subjects with experimental knee pain reduce knee loading by reducing extension moment, whereas lateral wedges have the opposite effect and increase the extension moment.

Experimental neck muscle pain increase pressure pain threshold over cervical facet joints

Abstract Aims Evaluate pressure pain threshold (PPT) over cervical facet joints before and after injection of experimental pain in the trapezius and multifidus muscles. Methods Fourteen healthy subjects (6 women) received randomized ultrasound-guided injections of hypertonic saline (5.8%), in the right multifidus muscle medial to C4/C5 facet joint and in the right trapezius muscle at the midpoint between C7 spinous process and acromion. The saline-induced pain intensity was assessed on a VAS scale. Before and during saline-induced pain PPTs were assessed by pressure algometry bilaterally over C2/C3 and C5/C6 facet joints. Three-way repeated-measures ANOVA with factors PPT location, injection site, and time was used for analysis. Post-hoc analysis was done by Bonferroni. Results Saline-induced trapezius muscle pain increased PPTs over all facet joints (P &lt; 0.05) compared with before pain. Saline-induced multifidus muscle pain increased PPTs bilaterally over C2/C3 facet joints and over the left C5/C6 facet joint (P &lt; 0.05) compared with before pain. Conclusions Trapezius muscle pain increased PPT over assessed facet joints. Similar results were found for multifidus muscle pain except for the right C5/C6 facet joint, which was close to the injection site. Such findings may reflect descending inhibitory control acting on structures furthest away from the painful structure.