Injection Of Hypertonic Saline Research Articles

Effects of deep brain stimulation and verbal suggestions on pain in Parkinson's disease.

In Parkinson's disease (PD) patients, verbal suggestions have been shown to modulate motor and clinical outcomes in treatment with subthalamic deep brain stimulation (DBS). Furthermore, DBS may alleviate pain in PD. However, it is unknown if verbal suggestions influence DBS' effects on pain. Twenty-four people with PD and DBS had stimulation downregulated (80-60 to 20%) and upregulated (from 20-60 to 80%) in a blinded manner on randomized test days: (1) with negative and positive suggestions of pain for down- and upregulation, respectively, and (2) with no suggestions to effect (control). Effects of DBS and verbal suggestions were assessed on ongoing and evoked pain (hypertonic saline injections) via 0-10 numerical rating scales along with motor symptoms, expectations, and blinding. Stimulation did not influence ongoing and evoked pain but influenced motor symptoms in the expected direction. Baseline and experimental pain measures showed no patterns in degree of pain. There was a trend toward negative suggestions increasing pain and positive suggestions decreasing pain. Results show significant differences in identical stimulation with negative vs positive suggestions (60% conditions AUC 38.75 vs 23.32, t(13) = 3.10, p < 0.001). Expectations to pain had small to moderate effects on evoked pain. Patients estimated stimulation level correctly within 10 points. Stimulation does not seem to influence ongoing and evoked pain, but verbal suggestions may influence pain levels. Patients appear to be unblinded to stimulation level which is an important consideration for future studies testing DBS in an attempted blind fashion.

Effects of intratesticular injection of hypertonic mannitol and saline on the quality of donkey sperm, indicators of oxidative stress and testicular tissue pathology

ObjectivesThe aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS).MethodsRandomly assigned to five treatment groups were 15 adult male donkeys: (1) Control group (no treatment), (2) Surgery group (surgical castration for testosterone control), (3) NS group (normal saline intratesticular injection), (4) HS group (hypertonic saline), and (5) HM group. We injected 20 mL per testicle. We took 5 mL blood from all donkeys before injection. Castration was performed under general anesthesia 60 days later. Samples included blood and testicular tissue. Total motility (TM), progressive motility (PM), movementy features, DNA damage, morphology, viability, and plasma membrane functionality were evaluated. Hormone analyses, histomorphometric studies and oxidative stress indices including total antioxidant capacity (TAC), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and NADP+/NADPH were evaluated. Apoptosis, pyroptosis-related Bax, Caspase-1, GSDMD, and Bcl-2 expression were also assessed.ResultsIn HS and HM groups, testosterone, epididymal sperm count, motility, viability, and plasma membrane functionality dropped while sperm DNA damage increased. HS and HM groups had significantly lower histomorphometric parameters, TAC, GPx, SOD, GSH, and Bcl-2 gene expression. MDA, NADP+/NADPH, Bax, Caspase-1, and GSDMD gene expression were substantially higher in the HS and HM groups than in the control group.ConclusionsToxic effects of hypertonic saline and mannitol on reproductive parameters were seen following, hence, they might be considered as a good chemical sterilizing treatment in donkeys.

Mirror Therapy Reduces Pain and Preserves Corticomotor Excitability in Human Experimental Skeletal Muscle Pain.

Approaches to preserve corticomotor excitability (CE) are attracting interest as a treatment for pain-induced changes in neural plasticity. We determined the effects of mirror therapy (MT) on skeletal muscle pain. Fifteen healthy adults who received hypertonic saline injections (5.8% NaCl, 0.2 mL) into the first dorsal interosseous (FDI) muscle of the right hand to induce experimental skeletal muscle pain were assigned to either the "MT and injection" or "injection only" group. Post-injection, the "MT and injection" group observed their left index finger abducting and adducting for 4 min, creating the illusion that the right index finger was moving. The "injection only" group remained at rest. CE and pain were assessed by measuring motor-evoked potentials (MEPs) of the right FDI triggered by transcranial magnetic stimulation and the numerical rating scale (NRS), respectively. MEP amplitudes were significantly higher in the "MT and injection" group, a trend that persisted post-MT intervention (MT intervention; p < 0.01, post-1; p < 0.05). The time for the NRS score to reach 0 was notably shorter in the "MT and injection" group (p < 0.05). Our preliminary results suggested that MT decreases CE and pain in skeletal muscles, potentially preventing neural plasticity changes associated with skeletal muscle pain and providing early pain relief.

Microglial involvement in ocular hypertension

Glaucoma, a chronic and multifactorial neurodegenerative disease, is the leading cause of irreversible blindness. It is characterized by the degeneration of retinal ganglion cells (RGCs), loss of their axons, and damage to the lamina cribrosa. To study glaucomatous optic neuropathy, experimental rodent models are commonly used due to their low cost, ease of handling, and similarities to the human retina. The ideal model must reproduce tissue changes observed in human glaucoma, such as alterations of the optic nerve head, thinning of the retinal nerve fibre layer, activation of glial cells, and progressive degeneration of RGCs.The DBA/2J transgenic mouse model is the most commonly used genetic model, characterized by a gradual increase in intraocular pressure (IOP) with age, leading to rapid and progressive loss of RGCs and optic nerve degeneration. However, limitations such as iris atrophy and peripheral anterior synechiae can alter the anterior segment and influence IOP measurement. Induced models of ocular hypertension (OHT) have a predictable IOP increase following experimental procedures, but this increase is usually rapid and sustained for a relatively short time, which may not represent the slow and sustained IOP elevation observed in primary open‐angle glaucoma. Nonetheless, induced models produce similar pathophysiological mechanisms to genetic models. Other models include the injection of hypertonic saline into episcleral veins to cause scarring of the trabecular meshwork and elevate IOP, and the intracameral injection of polystyrene or magnetic microbeads to obstruct normal drainage flow of aqueous humour, resulting in an IOP increase. A new model employs an intracameral injection of a cross‐linking polymer that produces a viscosity increase, impeding normal drainage of the aqueous humour and resulting in an IOP increase and loss of RGCs.In this SIS, we review the different glaucoma models, their methods, and the retinal tissue changes, with a focus on microglial cell changes.

Bilateral Corticomotor Reorganization and Symptom Development in Response to Acute Unilateral Hamstring Pain: A Randomized, Controlled Study

Accumulating evidence demonstrates that pain induces adaptations in the corticomotor representations of affected muscles. However, previous work has primarily investigated the upper limb, with few studies examining corticomotor reorganization in response to lower limb pain. This is important to consider, given the significant functional, anatomical, and neurophysiological differences between upper and lower limb musculature. Previous work has also focused on unilateral corticomotor changes in response to muscle pain, despite an abundance of literature demonstrating that unilateral pain conditions are commonly associated with bilateral motor dysfunction. For the first time, this study investigated the effect of unilateral acute hamstring pain on bilateral corticomotor organization using transcranial magnetic stimulation (TMS) mapping. Corticomotor outcomes (TMS maps), pain, mechanical sensitivity (pressure pain thresholds), and function (maximal voluntary contractions) were recorded from 28 healthy participants at baseline. An injection of pain-inducing hypertonic (n = 14) or pain-free isotonic (n = 14) saline was then administered to the right hamstring muscle, and pain ratings were collected every 30 seconds until pain resolution. Follow-up measures were taken immediately following pain resolution and at 25, 50, and 75 minutes post-pain resolution. Unilateral acute hamstring pain induced bilateral symptom development and changes in corticomotor reorganization. Two patterns of reorganization were observed—corticomotor facilitation and corticomotor depression. Corticomotor facilitation was associated with increased mechanical sensitivity and decreased function bilaterally (all P < .05). These effects persisted for at least 75 minutes after pain resolution. PerspectiveThese findings suggest that individual patterns of corticomotor reorganization may contribute to ongoing functional deficits of either limb following acute unilateral lower limb pain. Further research is required to assess these adaptations and the possible long-term implications for rehabilitation and reinjury risk in cohorts with acute hamstring injury.

The Use of Hypertonic Saline Injection in Peritonsillar Fossa during Monopolar Tonsillectomy

The Use of Hypertonic Saline Injection in Peritonsillar Fossa during Monopolar Tonsillectomy

Proteomics-Based Identification of Retinal Protein Networks Impacted by Elevated Intraocular Pressure in the Hypertonic Saline Injection Model of Experimental Glaucoma.

Elevated intraocular pressure is considered a major cause of glaucomatous retinal neurodegeneration. To facilitate a better understanding of the underlying molecular processes and mechanisms, we report a study focusing on alterations of the retina proteome by induced ocular hypertension in a rat model of the disease. Glaucomatous processes were modeled through sclerosing the aqueous outflow routes of the eyes by hypertonic saline injections into an episcleral vein. Mass spectrometry-based quantitative retina proteomics using a label-free shotgun methodology identified over 200 proteins significantly affected by ocular hypertension. Various facets of glaucomatous pathophysiology were revealed through the organization of the findings into protein interaction networks and by pathway analyses. Concentrating on retinal neurodegeneration as a characteristic process of the disease, elevated intraocular pressure-induced alterations in the expression of selected proteins were verified by targeted proteomics based on nanoflow liquid chromatography coupled with nano-electrospray ionization tandem mass spectrometry using the parallel reaction monitoring method of data acquisition. Acquired raw data are shared through deposition to the ProteomeXchange Consortium (PXD042729), making a retina proteomics dataset on the selected animal model of glaucoma available for the first time.

Intra- and interindividual reliability of muscle pain induced by an intramuscular injection of hypertonic saline injection into the quadriceps.

Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis. Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs. Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%). Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures. Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.

The Effect of Pre-Electroacupuncture on Nociceptive Discharges of Spinal Wide Dynamic Range Neurons in Rat.

Spinal wide dynamic range (WDR) neurons are well studied in pain models and they play critical roles in regulating nociception. Evidence has started to accumulate that acupuncture produces a good analgesic effect via activating different primary fibers with distinct intensities. The purpose of the present study was to compare the distinct intensities of pre-electroacupuncture (pre-EA) at local muscular receptive fields (RFs), adjacent or contralateral non-RFs regulating the nociceptive discharges of spinal WDR neurons evoked by hypertonic saline (HS). Spinal segments of electrophysiological recording were identified by neural tracers applied at the left gastrocnemius muscle. The thresholds of Aβ (TAβ), Aδ (TAδ) and C (TC) components of WDR neurons were measured to determine the intensity of pre-EA by extracellular recording. The discharges of WDR neurons induced by distinct intensities of pre-EA and 200 µL HS (6%) injection in left gastrocnemius muscle of rats were observed by extracellular recording. The spinal segments of WDR neurons were confirmed in lumbar (L)5-6 area according to the projective segments of dorsal root ganglion. TAβ, TAδ and TC of WDR neurons was determined to be 0.5, 1, and 2 mA, respectively. The pre-EA with intensities of TAβ (P < 0.05), TAδ (P < 0.05), TC (P < 0.05) or 2TC (P < 0.01) at ipsilateral adjacent non-RFs significantly reduced the discharges of WDR neurons, while at local RFs only pre-EA of TAδ (P < 0.05), TC (P < 0.05) and 2TC (P < 0.01) could inhibit the nociceptive discharges. In addition, intensity of pre-EA at contralateral non-RFs should reach at least TC to effectively inhibit the firing rates of WDR neurons (P < 0.01). Pre-EA could suppress nociceptive discharges of WDR neurons and the inhibitory effects were dependent on the distinct intensities and locations of stimulation.

The temporal expression of circulating microRNAs after acute experimental pain in humans.

MicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection. Twenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30minutes, 3hours, and 24hours post-injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no-pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate was p< 0.05. After 30minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24hours from baseline (p< 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli. This exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model. This exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow-up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.

Neuromuscular adaptations to experimentally induced pain in the lumbar region: systematic review and meta-analysis.

Experimental pain models are frequently used to understand the influence of pain on the control of human movement. In this systematic review, we assessed the effects of experimentally induced pain in the lumbar region of healthy individuals on trunk muscle activity and spine kinematics. Databases were searched from inception up to January 31, 2022. In total, 26 studies using either hypertonic saline injection (n = 19), heat thermal stimulation (n = 3), nociceptive electrical stimulation (n = 3), or capsaicin (n = 1) were included. The identified adaptations were task dependent, and their heterogeneity was partially explained by the experimental pain model adopted. Meta-analyses revealed an increase of erector spinae activity (standardized mean difference = 0.71, 95% confidence interval [CI] = 0.22-1.19) during full trunk flexion and delayed onset of transversus abdominis to postural perturbation tasks (mean difference = 25.2 ms, 95% CI = 4.09-46.30) in the presence of pain. Low quality of evidence supported an increase in the activity of the superficial lumbar muscles during locomotion and during voluntary trunk movements during painful conditions. By contrast, activity of erector spinae, deep multifidus, and transversus abdominis was reduced during postural perturbation tasks. Reduced range of motion of the lumbar spine in the presence of pain was supported by low quality of evidence. Given the agreement between our findings and the adaptations observed in clinical populations, the use of experimental pain models may help to better understand the mechanisms underlying motor adaptations to low back pain.

Motor Unit Recruitment is Altered When Acute Experimental Pain is Induced at a Site Distant to the Contracting Muscle

Acute pain alters motor unit discharge properties in muscles that are painful or influence loading of painful structures. Less is known about the changes in discharge when pain is induced in distant tissues that are unable or have limited capacity to modify the load of the contracting muscle. We aimed to determine whether acute experimental pain alters quadriceps motor unit discharge when pain is induced in; (i) a muscle that is unlikely to be mechanically influenced by modified quadriceps activity (tibialis anterior: TA), or (ii) the antagonist muscle (biceps femoris: BF). Using a within-subject design, 16 adults performed force-matched isometric knee extension during pain-free control conditions, and trials after painful hypertonic saline injections into TA or BF. Surface and intramuscular electromyography recordings were made. Despite maintained force, discharge rate of quadriceps motor units was lower during Pain than Control conditions for TA and BF trials (both P < 0.001). Redistribution of motor unit activity was observed; some units were recruited in control or pain but not both. As modified quadriceps motor unit discharge has limited/no potential to modify load in the painful tissue to protect the painful part, the findings might support an alternative hypothesis that activity is redistributed to larger motor units.

Deletion of Prorenin Receptor in the Rostral Ventrolateral Medulla Results in Biphasic and Sex‐Dependent Pressor Responses in Deoxycorticosterone Acetate‐salt Hypertension

In models of low renin hypertension such as the deoxycorticosterone acetate (DOCA)‐salt model, the local generation of angiotensin II in the brain mediates the increase in blood pressure. The prorenin receptor (PRR) might play a potential role in the local activation of prorenin in the brain. We have new evidence that prorenin and PRR are co‐expressed in the proximity to the rostral ventrolateral region of the medulla oblongata (RVL). Therefore, we hypothesized that selective ablation of PRR targeting the RVL attenuates responses to DOCA‐salt in mice. PRR ablation was targeted to the RVL by stereotactic microinjections of adeno‐associated virus (AAV) expressing Cre recombinase in PRR‐flox mice (PRRRVL‐KO). AAV mCherry was used as a control virus (WT). Pressor response to L‐glutamate in the injection site served as confirmatory stereotactic target hit. During the first week of DOCA‐salt treatment, RVL‐targeted ablation of PRR resulted in lower pressor responses to DOCA‐salt in females (WT=115±3 vs KO=104±4 mmHg; p&lt;0.05; n=8), but not males. However, after week 2 on DOCA‐salt treatment, female PRRRVL‐KO unexpectedly exhibited an exaggerated increase in systolic blood pressure (WT=149±3 vs KO=163±3 mmHg; p=0.004; n=8) and this was accompanied by a trending increase in urinary norepinephrine (WT=177±28 vs KO=270±38 ng/ml; p=0.07; n=7‐8). Next, female mice were challenged with an intraperitoneal hypertonic saline injection equivalent to 10% of their body weight followed by 4 hours of urine collection at baseline and on DOCA‐salt treatment. Urinary sodium excretion in female PRRRVL‐KO was significantly lower when compared to WT in both conditions (p&lt;0.05). Finally, using nuclear magnetic resonance/bioimpedance spectroscopy we assessed body fluid compartmentalization. We observed no difference in total body fluid among groups at any time point, but there was a significant mobilization of extracellular fluid to the intracellular compartment in PRRRVL‐KO. Our data indicate that the role of PRR in the RVL is sex‐dependent and biphasic. That is, PRR contributes to the pressor response during the initial stage of DOCA‐salt hypertension in females, presumably by facilitating the generation of angiotensin peptides in the RVL, while it plays a protective role by promoting renal sodium excretion and preventing blood pressure elevation during the maintenance stage of DOCA‐salt hypertension. This study also suggests that distinct PRR expressing cell populations within the RVL might elicit diverging physiological functions.

Preliminary results in comparison of caudal epidural injection of hyaluronidase versus hypertonic saline in managing lumbosacral canal stenosis: A randomized clinical trial

Background: Lumbosacral spinal stenosis (LSS) is one of the most common causes of back pain and disability. Its treatment varies from conservative and medical to surgical treatment, and the indications for its optimal management are not obviously defined. Epidural steroid injection is commonly used for pain relief in LSS. This study aims to compare the adjuvant efficacy of caudal epidural injection (CEI) of hyaluronidase with steroid versus hypertonic saline with steroid in patients with LSS. Methods: This clinical trial was done in a prospective, randomized, double-blind approach; it was conducted among 30 patients aged between 45 – 75 years who suffered from low back and leg pain in recent 6 months due to LSS. The patients were randomly allocated to two groups. Group A included 15 patients who received fluoroscopically guided CEI containing steroid, local anesthetic, and hyaluronidase, and Group B consisted of 15 patients who received fluoroscopically guided CEI containing steroid, local anesthetic, and hypertonic saline. The outcome measures included the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Quebec Back Pain Disability Scale (QBPDS), which were obtained from patients before the CEI as a baseline and after the second, fourth, and eighth weeks. Results: Before injection, there were no statistically significant differences between the two studied groups, neither in demographic characteristics nor in VAS, ODI, and QBPDS parameters. After injection, the mean of ODI and QBPDS improved from the baseline to the 2nd, 4th, and the 8th weeks in both groups (p &lt; 0.001) without any superiority between the two groups (p &gt; 0.05). However, there was a significant improvement of the mean VAS score through the second and fourth weeks in Group A (p = 0.032, 0.050). VAS score in the eighth week was equal without any superiority in both groups (p &gt; 0.05). Additionally, the mean social life status was significantly improved in group A in the 4th and 8th weeks after the intervention. Conclusions: In short-term follow-up, Caudal epidural injection of hyaluronidase, as well as hypertonic saline, seems to be effective in the management of LSS without any superiority in both materials. However, in the 2nd and 4th weeks after the procedure, better improvement of means VAS score was observed in the hyaluronidase group.

The effect of hypertonic saline evoked muscle pain on neurophysiological changes and exercise performance in the contralateral limb

Non-local muscle pain may impair endurance performance through neurophysiological mechanisms, but these are relatively unknown. This study examined the effects of muscle pain on neuromuscular and neurophysiological responses in the contralateral limb. On separate visits, nine participants completed an isometric time to task failure (TTF) using the right knee extensors after intramuscular injection of isotonic saline (CTRL) or hypertonic saline (HYP) into the left vastus lateralis. Measures of neuromuscular fatigue were taken before, during and after the TTF using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation. Mean pain intensity was greater in the left leg in HYP (3.3 ± 1.9) compared to CTRL (0.4 ± 0.7; P < 0.001) which was combined with a reduced TTF by 9.8% in HYP (4.54 ± 0.56 min) compared to CTRL (5.07 ± 0.77 min; P = 0.005). Maximum voluntary force was not different between conditions (all P > 0.05). Voluntary activation was lower in HYP compared to CTRL (P = 0.022). No difference was identified between conditions for doublet amplitude (P > 0.05). Furthermore, no difference in MEP·Mmax−1 or the TMS silent period between conditions was observed (all P > 0.05). Non-local pain impairs endurance performance of the contralateral limb. This impairment in performance is likely due to the faster attainment of the sensory tolerance limit from a greater amount of sensory feedback originating from the non-exercising, but painful, left leg.

Systemic hypertonic saline enhances glymphatic spinal cord delivery of lumbar intrathecal morphine

The blood-brain barrier significantly limits effective drug delivery to central nervous system (CNS) targets. The recently characterized glymphatic system offers a perivascular highway for intrathecally (i.t.) administered drugs to reach deep brain structures. Although periarterial cerebrospinal fluid (CSF) influx and concomitant brain drug delivery can be enhanced by pharmacological or hyperosmotic interventions, their effects on drug delivery to the spinal cord, an important target for many drugs, have not been addressed. Hence, we studied in rats whether enhancement of periarterial flow by systemic hypertonic solution might be utilized to enhance spinal delivery and efficacy of i.t. morphine. We also studied whether the hyperosmolar intervention affects brain or cerebrospinal fluid drug concentrations after systemic administration. Periarterial CSF influx was enhanced by intraperitoneal injection of hypertonic saline (HTS, 5.8%, 20 ml/kg, 40 mOsm/kg). The antinociceptive effects of morphine were characterized, using tail flick, hot plate and paw pressure tests. Drug concentrations in serum, tissue and microdialysis samples were determined by liquid chromatography-tandem mass spectrometry. Compared with isotonic solution, HTS increased concentrations of spinal i.t. administered morphine by 240% at the administration level (T13–L1) at 60 min and increased the antinociceptive effect of morphine in tail flick, hot plate, and paw pressure tests. HTS also independently increased hot plate and paw pressure latencies but had no effect in the tail flick test. HTS transiently increased the penetration of intravenous morphine into the lateral ventricle, but not into the hippocampus. In conclusion, acute systemic hyperosmolality is a promising intervention for enhanced spinal delivery of i.t. administered morphine. The relevance of this intervention should be expanded to other i.t. drugs and brought to clinical trials.

Dose-Dependent Pain and Pain Radiation after Chemical Stimulation of the Thoracolumbar Fascia and Multifidus Muscle: A Single-Blinded, Cross-Over Study Revealing a Higher Impact of Fascia Stimulation.

Acute low back pain can be experimentally induced by injections of hypertonic saline into deep tissues of the back, such as fascia and muscle. The current study investigated the dose-dependency of peak-pain and spatial extent of concomitant radiating pain following 50, 200 and 800 μL bolus injections of hypertonic saline (5.8%) into the thoracolumbar fascia and multifidus muscle, since data on dose-dependency is lacking in humans. Sixteen healthy subjects rated (11 female, 5 male; 23.3 ± 3.1 years, mean ± SD) intensity and spatial extent of pain. Injections into the fascia resulted in significantly higher peak-pain (+86%, p < 0.001), longer pain durations (p < 0.05), and larger pain areas (+65%, p < 0.02) and were less variable than intramuscular injections. Peak-pain ratings and pain areas were 2–3-fold higher/larger for 200 μL vs. 50 μL. In contrast, peak pain increased only marginally at 800 μL by additional 20%, while pain areas did not increase further at all in both, fascia and muscle. Thus, higher injection volumes did also not compensate the lower sensitivity of muscle. Peak-pain ratings and pain areas correlated between fascia and muscle (r = 0.530, p < 0.001 and r = 0.337, p < 0.02, respectively). Peak-pain ratings and pain areas correlated overall (r = 0.490, p < 0.0001), but a weak correlation remained when the impact of between-tissue differences and different injection volumes were singled out (partial r = 0.261, p < 0.01). This study shows dose-dependent pain responses of deep tissues where an injection volume of 200 μL of hypertonic saline is deemed an adequate stimulus for tissue differentiation. We suggest that pain radiation is not simply an effect of increased peripheral input but may afford an individual disposition for the pain radiation response. Substantially higher pain-sensitivity and wider pain areas support fascia as an important contributor to non-specific low back pain.

Interhemispheric Inhibition Between Primary Sensory Cortices is not Influenced by Acute Muscle Pain

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Altered interhemispheric inhibition (IHI) between primary sensory cortices (S1s) is one mechanism that could explain this phenomenon. However, IHI between S1s in response to acute muscle pain, and the relationship between IHI and pressure pain sensitivity in the unaffected limb have not been examined. In 21 healthy individuals, IHI was assessed using somatosensory evoked potentials in response to paired median nerve electrical stimulation at: 1) baseline; 2) immediately following pain resolution; and 3) at 30-minutes follow-up. Acute muscle pain was induced by injection of hypertonic saline into the right abductor pollicis brevis (APB) muscle. Pressure pain thresholds were assessed at the right and left APB muscles before and 30-minutes after pain resolution. Compared to baseline, IHI from the affected to unaffected S1 was unaltered in response to acute muscle pain immediately following pain resolution, or at 30-minutes follow-up. Pressure pain thresholds were reduced over the right (P = .001) and left (P = .001) APB muscles at 30-minutes follow-up. These findings suggest IHI between S1s is unaffected by acute, short-lasting muscle pain, despite the development of increased sensitivity to pressure in the unaffected APB muscle. PerspectiveIHI from the affected S1 (contralateral to the side of pain) to unaffected S1 is unaltered following the resolution of acute muscle pain. This finding suggests that IHI between S1s may not be relevant in the development of bilateral sensorimotor symptoms in unilateral pain conditions.

VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma

AbstractPurposeThere is an unmet need for new drugs in glaucoma that can effectively prevent glaucoma progression. We assessed the effects of VSN16S and AG‐020, the agonists of the cannabinoid receptor, on intraocular pressure (IOP) and neuroprotection using a rat model of ocular hypertension (OHT).Methods20 male Dark Agouti (DA) rats aged 8–10 weeks were randomly located into 4 groups (n = 5): OHT‐only, OHT+vehicle, OHT+VSN16S, and OHT+AG‐020. All animals had IOP surgically elevated in the left eye (OS) by injection of hypertonic saline into the episcleral veins. Except for OHT‐only, animals in the other 3 groups have received eye drops in OS either vehicle or VSN16S or AG‐0202 at 10 mg/ml, twice daily for 3 weeks following OHT‐induction. IOPs were recorded in both eyes at baseline (BL), day1, week1, 2, and 3 using a Tonopen. Animals were in vivo imaged for retinal ganglion cell (RGC) apoptosis in both eyes using DARC (Detection of Apoptotic Retinal Cells) at BL and week3 before culled. Retinal whole‐mounts were immunostained with a Brn‐3a antibody to assess RGC survival. DARC spots and RGC counts were assessed by blinded algorithm analysis.ResultsSurgical procedure induced a significant increase in IOP profiles in all animal groups compared to the contralateral eye (OD), and peak levels occurred at day1 (p &lt; 0.001). In the OHT eyes treated with VSN16S, IOPs at week1 exhibited a sharp reduction (p &lt; 0.05), and integrate IOP at week3 was significantly lower than vehicle controls (p &lt; 0.01). However, AG020 showed no effect on IOP. IOP elevation resulted in a significant increase in DARC counts (RGC apoptosis) in all groups, compared to the baseline. DARC counts revealed a significant reduction in the OHT eyes treated by VSN16S, compared to the OHT‐only and vehicle groups (p &lt; 0.01), but less of a reduction of DARC counts was observed with AG‐020 treatment (p &lt; 0.05). A significant reduction of Brn‐3a+RGC density was seen in the OHT‐only group compared to naïve controls (p &lt; 0.05), and VSN16S treatment demolished the difference although no significance was found on Brn‐3a+RGC density between VSN16S and controls.ConclusionsVSN16S exerted neuroprotective properties in OHT‐induced RGC loss, which may be associated with lowering IOP profiles. DARC is a useful tool in the assessment of drug efficacy in retinal neurodegenerative diseases.

Epidural steroid injection of hypertonic saline for degenerative lumbar spinal stenosis: A randomized controlled trial

Epidural steroid injection of hypertonic saline for degenerative lumbar spinal stenosis: A randomized controlled trial