Intrathecal Baclofen Injection Research Articles

Pendulum test parameters are useful for detecting knee muscle hypertonia and quantifying response to an intrathecal baclofen bolus injection.

Our objective was to determine which pendulum test parameters are useful for detecting hypertonia in the knee muscles and assessing the group and individual responses to intrathecal baclofen (ITB) bolus injection among prospective pump recipients. We included 15 neurological patients with lower limb hypertonia (mainly spinal cord injury, n = 7) and collected data the day before (baseline), and 2.5 and 5.0 h after the 50-µg ITB bolus injection. For comparison, data were collected in 15 healthy controls. The average over six test repetitions was obtained for the number of oscillations, swing time (SwingT), amplitudes of the first flexion and extension, maximum angular velocities of the first flexion (F1V) and extension (E1V), relaxation index, and damping coefficient (DampC). Across the patient group, all pendulum parameters indicated a significant decrease in hypertonia from baseline to postinjection (analysis of variance P ≤ 0.004), except DampC. On the basis of the cutoffs from the receiver operating characteristic curve, all parameters were good or excellent discriminators of hypertonia in patients from normotonia in controls (area under the curve ≥0.85), with the highest sensitivity for SwingT and E1V (≥93%). Furthermore, all parameters except F1V revealed a significant shift from preinjection hypertonia to postinjection normotonia among patients (McNamar test P ≤ 0.002, DampC excluded due to missing data), with the greatest responsiveness for E1V and relaxation index (≥73%). The results confirm the overall usefulness of pendulum test parameters in this patient population and indicate that some parameters are better at detecting hypertonia (SwingT, E1V) whereas others (E1V, relaxation index) are more responsive to the ITB injection.

Activation of GABAB Receptor Suppresses Diabetic Neuropathic Pain through Toll-Like Receptor 4 Signaling Pathway in the Spinal Dorsal Horn.

Diabetic neuropathic pain (DNP) is a prevalent complication in diabetes patients. Neuronal inflammation and activation of Toll-like receptor 4 (TLR4) are involved in the occurrence of DNP. However, the underlying mechanisms remain unclear. Downregulation of gamma-aminobutyric acid B (GABAB) receptor contributes to the DNP. GABAB receptor interacts with NF-κB, a downstream signaling factor of TLR4, in a neuropathic pain induced by chemotherapy. In this study, we determined the role of TLR4/Myd88/NF-κB signaling pathways coupled to GABAB receptors in the generation of DNP. Intrathecal injection of baclofen (GABAB receptor agonist), LPS-RS ultrapure (TLR4 antagonist), MIP (MyD88 antagonist), or SN50 (NF-κB inhibitor) significantly increased paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) in DNP rats, while intrathecal injection of saclofen (GABAB receptor blocker) decreased PWT and PWTL in DNP rats. The expression of TLR4, Myd88, NF-κBp65, and their downstream components IL-1 and TNF-α was significantly higher in the spinal cord tissue in DNP rats compared to control rats. Following inhibition of TLR4, Myd88, and NF-κB, the expression of IL-1 and TNF-α decreased. Activation of GABAB receptors downregulated the expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. Blockade of GABAB receptors significantly upregulated expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. These data suggest that activation of the TLR4/Myd88/NF-κB signaling pathway is involved in the occurrence of DNP in rats. Activation of GABAB receptor in the spinal cord may suppress the TLR4/Myd88/NF-κB signaling pathway and alleviate the DNP.

Case Series: Intrathecal Baclofen Therapy in Stiff-Person Syndrome

Stiff-person syndrome (SPS) is associated with axial rigidity superimposed on sustained muscle spasms. These symptoms commonly interfere with the performance of activities of daily living including ambulation. This retrospective case series evaluates the outcomes of screening tests and chronic infusion of intrathecal baclofen (ITB) in patients diagnosed with SPS treated in our spasticity clinic. Patients were identified from an institutional review board-approved clinical registry of ITB therapy. Data from clinical encounters were extracted from the registry and from the patients' electronic medical record. All patients with medically refractory spasticity related to SPS screened with an ITB injection were included. In addition to pertinent demographic and clinical information, data from validated outcome measures routinely used in the clinic were collected: pain Numeric Rating Scale, Spasm Frequency Scale, lower extremity Modified Ashworth Scale (MAS), and Timed 25 Foot Walk. Outcomes data for chronic ITB infusion were assessed at early (<6 months) and late follow-up (6-12 months) visits after surgery. Nine patients were included, and seven received chronic ITB infusion. MAS scores were improved at early and late follow-up, and five patients experienced a reduction in pain scores. Walking performance remained stable in previously ambulatory patients. Four patients experienced complications related to ITB implantation, which resolved with medical or surgical treatment. Consistent with other case series, our results suggest that ITB is an effective therapy for medically intractable spasticity due to SPS, and symptom reduction can be achieved without compromising ambulation.

Improved response after intrathecal administration of baclofen in a patient with impaired consciousness – A case study

Disorders of consciousness present some of the most difficult diagnostic and therapeutic challenges in brain rehabilitation. Within the spectrum of these disorders, diagnosis remains clinical and depends on the response to various stimuli in the environment rather than objective physiological markers. In recent years, various cases have been reported in the medical literature in which patients with such diagnoses reacted to various stimuli indirectly. Spasticity is a common sequela of brain injury and may significantly impair a patient's ability to respond to stimuli in their environment. A case study of a patient in a state of minimal reactivity demonstrating significantly improved responses to their environment following intrathecal injection of Baclofen. A 59-year-old man who was admitted for rehabilitation following subarachnoid hemorrhage secondary to anterior coronary artery aneurysm (ACA) requiring subsequent periventricular shunt placement. At admission, the patient presented in a vegetative state. During hospitalization, there was a temporary improvement in level of consciousness until the appearance of infection along the VPS drain necessitating removal of the shunt. Upon completion of treatment, the patient returned to our department with inconsistent, minimal reactivity on exam. Due to severe spasticity in all four limbs unresponsive to oral treatment and local injection, a one-time intrathecal injection of Baclofen was administered. Directly following treatment, the patient demonstrated decreased tone and immediate improvement in responsiveness and ultimately the production of a number of intelligible words and phrases. In evaluating patients suffering from disorders of consciousness, it is important to recognize that limited responsiveness results not only from the impairment of information reception, processing, and response initiation, but also from tonal disturbances that may be causing difficulty in performing such movements. This case study supports previous literature demonstrating improved communication following cellophane pump implantation following severe head injury.

Intrathecal Baclofen Injection to Avoid Withdrawal in a Multiple Sclerosis Patient Undergoing Lumbar Spine Surgery: A Case Report.

Spasticity of spinal or cerebral origin is frequently treated with baclofen. Treatment interruption initially results in rebound spasticity; life-threatening withdrawal symptoms may follow. Severe rebound spasticity of leg muscles occurred in a multiple sclerosis patient after a 10-hour long perioperative pause of oral baclofen intake. In a subsequent spine surgery, recurrence was prevented by substituting a cumulative 12-hour oral baclofen dose with an intraoperative intrathecal injection. Administration of intrathecal baclofen during prolonged surgery in patients dependent on oral baclofen may improve patient comfort and prevent early withdrawal symptoms. The most optimal conversion ratio from oral to intrathecal baclofen is still undetermined.

Poster 373 Paradoxically Increased Rigidity After Intrathecal Baclofen Injection in a Patient with Multiple Sclerosis: A Case Report.

Poster 373 Paradoxically Increased Rigidity After Intrathecal Baclofen Injection in a Patient with Multiple Sclerosis: A Case Report.

The positive allosteric GABAB receptor modulator rac-BHFF enhances baclofen-mediated analgesia in neuropathic mice

Neuropathic pain is associated with impaired inhibitory control of spinal dorsal horn neurons, which are involved in processing pain signals. The metabotropic GABAB receptor is an important component of the inhibitory system and is highly expressed in primary nociceptors and intrinsic dorsal horn neurons to control their excitability. Activation of GABAB receptors with the orthosteric agonist baclofen effectively reliefs neuropathic pain but is associated with severe side effects that prevent its widespread application. The recently developed positive allosteric GABAB receptor modulators lack most of these side effects and are therefore promising drugs for the treatment of pain. Here we tested the high affinity positive allosteric modulator rac-BHFF for its ability to relief neuropathic pain induced by chronic constriction of the sciatic nerve in mice. rac-BHFF significantly increased the paw withdrawal threshold to mechanical stimulation in healthy mice, indicating an endogenous GABABergic tone regulating the sensitivity to mechanical stimuli. Surprisingly, rac-BHFF displayed no analgesic activity in neuropathic mice although GABAB receptor expression was not affected in the dorsal horn as shown by quantitative receptor autoradiography. However, activation of spinal GABAB receptors by intrathecal injection of baclofen reduced hyperalgesia and its analgesic effect was considerably potentiated by co-application of rac-BHFF. These results indicate that under conditions of neuropathic pain the GABAergic tone is too low to provide a basis for allosteric modulation of GABAB receptors. However, allosteric modulators would be well suited as an add-on to reduce the dose of baclofen required to achieve analgesia.

Effect of Intrathecal Baclofen Bolus Injection on Ankle Muscle Activation During Gait in Patients With Acquired Brain Injury

Background. Intrathecal baclofen (ITB) bolus injection effectively decreases spinal excitability but the impact on lower limb muscle activation during gait has not been thoroughly investigated. Objective. Examine activation of medial gastrocnemius (MG) and tibialis anterior (TA) muscles during gait before and after ITB bolus injection in patients with resting hypertonia after acquired brain injury. Methods. Lower extremity Ashworth score, temporospatial gait parameters, characteristics of the linear relationship between electromyogram (EMG) and lengthening velocity (LV) in MG during stance, and the duration and magnitude of TA-MG coactivation were assessed before and at 2, 4, and 6 hours after a 50-µg ITB injection via lumbar puncture in 8 hemorrhagic stroke and 11 traumatic brain injury subjects. Results. Temporospatial gait parameters did not significantly differ across the evaluation points (P ≥ .170). However, Ashworth score (P < .001), frequency and gain of significant positive EMG-LV slope (P ≤ .020), and duration of TA-MG coactivation (P ≤ .013) significantly decreased in the more-affected leg after ITB bolus. EMG changes were not significantly different between patients who did (n = 10) and did not (n = 9) increase gait speed after the injection. The timing of the largest decrease in Ashworth score and the largest decrease in EMG parameters coincided in 36% of cases, on average. Conclusions. ITB bolus injection alters the activation of MG and TA during gait. However, the changes in muscle activation are not closely related to the changes in gait speed or resting muscle hypertonia. The analysis of ankle muscle activation during gait better characterizes the response to ITB bolus injection than gait kinematics.

Activation of spinal GABAB receptors normalizes N-methyl-D-aspartate receptor in diabetic neuropathy

N-methyl-D-aspartate receptor (NMDAR) activity is increased, while GABAB receptor is downregulated in the spinal cord dorsal horn in diabetic neuropathy. In this study, we determined the interaction of NMDARs and GABAB receptors in streptozotocin (STZ)-induced diabetic neuropathy. The paw withdrawal threshold (PWT) was significantly lower in STZ-treated rats than in vehicle-treated rats. Intrathecal injection of baclofen, a GABAB receptor agonist, significantly increased the PWT in STZ-treated rats, an effect that was abolished by pre-administration of the GABAB receptor specific antagonist CGP55845. Spinal NR2B, an NMDA receptor subunit, protein and mRNA expression levels were significantly higher in STZ-treated rats than in vehicle-treated rats. Intrathecal baclofen significantly reduced the NR2B protein and mRNA expression levels in STZ-treated rats. Intrathecal administration of CGP55845 eliminated baclofen-induced reduction of NR2B protein and mRNA levels in STZ-treated rats. In addition, the phosphorylated cAMP response element-binding (CREB) protein level was significantly higher in the spinal cord dorsal horn in STZ-treated rats compared with vehicle-treated rats. Intrathecal injection of baclofen significantly decreased phosphorylated CREB protein level in STZ-treated rats; an effect was blocked by CGP55845. These data suggest that activation of GABAB receptors in the spinal cord dorsal horn normalizes NMDAR expression level in diabetic neuropathic pain.

Spinal Cord Stimulation and Intrathecal Baclofen Therapy: Combined Neuromodulation for Treatment of Advanced Complex Regional Pain Syndrome

Objective: Spinal cord stimulation (SCS) is one of the widely used procedures for the treatment of complex regional pain syndrome (CRPS). However, complete pain relief is rarely achieved, and the SCS effect diminishes over time. Recently intrathecal baclofen (ITB) therapy is reported to be a modality for treating fixed dystonia related to CRPS. Other reports have suggested that ITB therapy can enhance the effect of SCS in patients with neuropathic pain. We report the effectiveness of combined SCS and ITB therapy, focusing on the role of ITB therapy as an adjunctive therapy for controlling symptoms of advanced CRPS. Methods: Five affected extremities of 4 patients with CRPS (2 male; mean age, 32.5 years) refractory to conservative treatment were evaluated retrospectively. Three patients underwent SCS implantation first, with ITB pumps being implanted a few years later. Bolus ITB injection was administered under temporary percutaneous SCS in 1 patient. Pain intensity was evaluated using the visual analogue scale (VAS) before and after ITB administration. Results: Pain relief of more than 50% was observed in the upper extremity of 1 patient and one of more than 30% was observed in 2 patients. The mean pain reduction rate in all 4 patients was 28.9% before and 43.8% after treatment. All patients, including those without any improvements in VAS score, showed decreased postural abnormalities after combined SCS and ITB therapy. Improvement in postural abnormalities, such as fixed dystonia or paroxysmal tremor-like movements, resulted in overall pain relief by reducing pain fluctuations. Conclusions: Combined SCS and ITB neuromodulation decreases pain intensity in refractory CRPS cases or improves associated abnormal dystonic posture and movement disorders and reduces pain fluctuations.

Optimized double emulsion-solvent evaporation process for production of solid lipid nanoparticles containing baclofene as a lipid insoluble drug

Intrathecal injection of baclofen is the reference treatment for severe spasticity of cerebral-spinal origin. Solid lipid nanoparticles (SLNs) could be considered as a beneficial delivery system for enhancing penetration of drug through the blood brain barrier (BBB). In this study, baclofen- loaded SLNs were prepared using double emulsification-solvent evaporation method and a Box-Behnken design, based on three independent variables, was used to reduce the number of required experiments. Variable parameters were drug/lipid ratio, w/o phase ratio and the amount of surfactant. It was deduced that SLNs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity could be produced by this method and experimental design method could be useful for predicting optimum baclofen loaded SLNs with minimum numbers of experiments. Characterization of optimum formulation, provided by evaluation of experimental data, showed no significant difference between calculated and measured data.

Effectiveness of GABA agonist for treatment in mice with complete freud’s adjuvants induced chronic pain: molecular modeling approach

The present study was designed to investigate the effectiveness of gaba agonist in behavioral changes of inflammatory mice with molecular docking approach. Forty mice were divided into 8 groups i.e. sham, gabapentin (10, 30 and 100 nmol), baclofen (1, 10 and 30 nmol) and negative control. Chronic pain was induced by inflammatory agent such as Complete Freud’s Adjuvant (CFA). On day 8 after intraplantar injection of CFA, mice were treated by intrathecal with normal saline (sham and negative control groups), gabapentin and baclofen with three different doses, once a day for seven consecutive days. Latency time toward thermal stimulus was measured on days 1,2,8,9,11 and 15 after induction. The molecular docking was examined by Mollegro virtual docker program. The result showed that intrathecal injection of gabapentin and baclofen increased time latency toward thermal stimulus compared to negative control. There were differences between gabapentin and baclofen doses for chronic pain treatment. Molecular docking showed that the differences of effective dose were related to type of amino acid binding between gabapentin and baclofen.DOI: http://dx.doi.org/10.3329/icpj.v2i2.13194 International Current Pharmaceutical Journal 2013, 2(2): 29-32

Novel epidural baclofen infusion trial for intractable spasticity with long-term follow-up observation and a focused review of the literature

Background Intrathecal baclofen (ITB) infusion has been increasingly used in patients with intractable spasticity. Prior to the implantation of the permanent pump, a trial is usually conducted to document efficacy. Intrathecal bolus injection of baclofen, followed by serial evaluations to confirm the improvement of spasticity, has been most commonly used during such trials. However, for patients who refused to undergo ITB trial injection due to previous untoward complications such as intractable headache, there has been no other alternatives. Objective To report the first case of a successful epidural baclofen infusion trial, conducted as outpatient in a lady with severe spasticity due to multiple sclerosis; to report the long term follow-up observation (3 years) following the permanent intrathecal pump placement; and to conduct a focused review of the literature pertaining to epidural baclofen. Design Case report. Setting: Tertiary-care pain clinic. Case Report: A 62-year-old female with progressive spasticity of bilateral lower extremities and left upper extremity due to multiple sclerosis, not responding to multiple oral antispasticity drugs, was referred to clinic for ITB therapy. The patient adamantly declined ITB bolus trial due to previous episode of severe headache following lumbar puncture. Thus an outpatient epidural baclofen infusion was performed and was successful. Based on the positive response from the epidural infusion trial, a permanent IT pump was subsequently placed and the patient has had sustained reduction of her spasticity since pump implantation 3 years ago. Limitation: Single center case report. Conclusion In patients who are reluctant to the ITB bolus trial due to previous complication such as headache, an outpatient epidural baclofen infusion trial, when done properly, can serve as an alternative approach to the ITB trial and provides needed information

Influence of Intraventricular Application of Baclofen on Arterial Blood Pressure and Neurotransmitter Concentrations in the Hypothalamic Paraventricular Nucleus of Rats

The hypothalamic paraventricular nucleus (PVN) is a key site for regulating neuroendocrine functions in the magnocellular part and autonomic activities in the parvocellular part. Its anatomical proximity to the third ventricle could be a good target for intrathecal injection of baclofen. We investigated the correlation of intrathecal application of baclofen (a specific GABAB receptor agonist) and the release of epinephrine, norepinephrine, dopac, homovanillinic acid (HVA), glutamate and aspartate from the PVN. The decomposition products HVA, dopa and dopac of norepinephrine, epinephrine and dopamine, respectively, were used as parameters for the secretion of dopamine. We implanted a microdialysis probe in the PVN of 25 Wistar rats. In 13 rats, 1.5 μg baclofen was injected in the lateral ventricle and the equivalent quantity of Ringer's lactate solution injected in the remaining 12 rats as a control group. Neurotransmitters and amino acids were quantified by high-performance liquid chromatography. There was a conspicuous but not significant effect of baclofen concerning the secretion of epinephrine, norepinephrine, dopac, glutamate and aspartate from the PVN. A significant increase in HVA concentration was observed only in rats treated with baclofen compared with the control group. These findings suggest that baclofen influences the secretion of neurotransmitters and amino acids involved in autonomic activities mediated by GABAB receptors.

Intrathecal Baclofen Facilitated Postanesthetic Tracheal Extubation in a Dystonic Patient Associated with Neurodegeneration of Brain Iron Accumulation (Hallervorden-Spatz Disease)

Patients with Hallervorden-Spatz disease may be confronted by invasive procedure, like gastrostomy and thalamotomy for care of the status of extreme dystonia and rigidity. This rare disorder possesses potential perioperative risks, such as difficult airway management, aspiration pneumonia, hyperpyrexia, dehydration, acute renal failure, and postoperative pulmonary insufficiency. As patients were usually in the state of uncontrollable dystonia and rigidity, delayed endotracheal extubation had been suggested by several previous case reports. We report the anesthetic management of a 34-year-old Hallervorden-Spatz disease woman scheduled for intrathecal baclofen pump implantation under general anesthesia. Preoperatively she had suffered from severe dystonia, confusion and repeated attacks of respiratory insufficiency and pneumonia requiring mechanical ventilation and critical care. Anesthesia was induced uneventfully and the catheter of the pump reached the CSF via T2 interspace. Intraoperative intrathecal baclofen injection mildly relieved her severe dystonia and rigidity. Hemodynamics and arterial blood gas were improved than preoperative. She was extubated after consciousness was regained. Postanesthetic visit demonstrated a fair outcome. Whether this treatment applies to every case confronted by general anesthesia needs to be elucidated. Nevertheless, we suggest intrathecal baclofen may help postanesthetic pulmonary care by attenuating dystonia and rigidity and can be an adjuvant for anesthesia care in patients with Hallervorden-Spatz disease.

37. H-reflex and F-wave of the patients of spinal cord injury before and after intrathecal baclofen injection

37. H-reflex and F-wave of the patients of spinal cord injury before and after intrathecal baclofen injection

The occurrence of the Babinski sign in complete spinal cord injury

The purpose of the present study was to explore factors that influence the occurrence of the Babinski sign (BS) in complete spinal cord injury patients. At Balgrist University Hospital, Zurich, Switzerland, thirty-five subjects suffering from a complete traumatic spinal cord injury (ASIA A) were examined for the occurrence of the BS, tendon reflex excitability and spastic muscle tone (Modified Ashworth Scale). Five subjects were acute/subacute (1-6 months after spinal cord injury (SCI)), 30 were chronic (SCI > 1 year). In one subject, the measures were examined before and after injection of intrathecal Baclofen. Subjects with a negative BS were investigated electrophysiologically for possible peripheral nerve damage. In 17 subjects (49%), the BS was present, while it was absent in 18 subjects (51%). The occurrence of the BS did not depend on the level of lesion. Most patients with a positive BS also presented a high spastic muscle tone, while those with a negative BS showed low level or absent spastic muscle tone. In 11 SCI subjects, absence of the BS was associated with peripheral nerve damage. In one patient, the BS along with spastic signs disappeared after intrathecal injection of Baclofen. In complete SCI subjects, the occurrence of the BS is connected with spastic muscle tone. The absence of the BS is frequently due to associated peripheral nerve damage.

Reciprocal inhibition between Gal1 and GABAB receptors: functional implications in neuropathic pain sensitization

Event Abstract Back to Event Reciprocal inhibition between Gal1 and GABAB receptors: functional implications in neuropathic pain sensitization Rabia Bouali-Benazzouz1, 2*, Frederic Naudet1, 2, Yves Lefeuvre1, 2, Alexandre Favereaux1, 2, Zhi-Qinq Xu3, Frédéric Nagy1, 2 and Marc Landry1, 2 1 Neurocentre Magendie, INSERM U862 , Physiopathologie des reseaux neuronaux medullaires , France 2 Universite de Bordeaux, France 3 Karolinska Institutet, Department of Neurosciences, Sweden In dorsal spinal horn, nociceptive transmission is controlled by excitatory and inhibitory modulations. Our general objective is to study desinhibition processes that may disrupt this balance and cause pain sensitization. Beside classical neurotransmitters, neuropeptides also contribute to inhibitory modulations. Galanin is such an inhibitory peptide released from primary afferents and from local GABAergic interneurons. GABA and Galanin metabotropic receptors, GABAB and Gal1 respectively, initiate similar intracellular events and share the same intracellular targets. In the present study, we investigated whether co-activation of these two inhibitory systems cooperate in limiting neuropathic pain sensitization. Intrathecal injection of either Baclofen or Galanin, GABAB and Gal1 agonists respectively, reduced mechanical and cold allodynia in neuropathic rats. Surprisingly, the co-injection of Baclofen and Galanin together totally abolished these inhibitory effects. Colocalisation of GABAB and Gal1 mRNAs in spinal neurons suggests direct interactions between both receptors. Moreover, [35S] GTP gamma S binding assay showed cross-suppression of receptor-induced cellular signalling in superficial laminae. In vitro patch clamp electrophysiology demonstrated that galanin abolished Baclofen-induced potassium currents in spinal cord cultures. Taken together, these data confirmed the above hypothesis of direct interactions between receptors. Finally, we showed physical interaction between Gal1 and GABAB2 subunit by using co-immunoprecipitation and FRET/FLIM imaging. Our study provides direct evidence of peptidergic modulatory roles on classical neurotransmission. More importantly, it suggests a new mechanism for controlling GABAB activity, through direct interaction with other metabotropic receptors. Moreover, it demonstrates behavioural implications of such interactions in processes leading to pain sensitization. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Citation: Bouali-Benazzouz R, Naudet F, Lefeuvre Y, Favereaux A, Xu Z, Nagy F and Landry M (2009). Reciprocal inhibition between Gal1 and GABAB receptors: functional implications in neuropathic pain sensitization. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.172 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Nov 2009; Published Online: 26 Nov 2009. * Correspondence: Rabia Bouali-Benazzouz, Neurocentre Magendie, INSERM U862, Physiopathologie des reseaux neuronaux medullaires, Bordeaux, France, rabia.benazzouz@bordeaux.inserm.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rabia Bouali-Benazzouz Frederic Naudet Yves Lefeuvre Alexandre Favereaux Zhi-Qinq Xu Frédéric Nagy Marc Landry Google Rabia Bouali-Benazzouz Frederic Naudet Yves Lefeuvre Alexandre Favereaux Zhi-Qinq Xu Frédéric Nagy Marc Landry Google Scholar Rabia Bouali-Benazzouz Frederic Naudet Yves Lefeuvre Alexandre Favereaux Zhi-Qinq Xu Frédéric Nagy Marc Landry PubMed Rabia Bouali-Benazzouz Frederic Naudet Yves Lefeuvre Alexandre Favereaux Zhi-Qinq Xu Frédéric Nagy Marc Landry Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Aseptic meningitis after intrathecal baclofen injection

Two case reports of aseptic meningitis after intrathecal baclofen injection. To report an unusual complication of intrathecal baclofen injection during test injections. Department of Neurological Rehabilitation, R Poincaré Hôpital (Paris-Ile de France-Ouest University). We present two cases of chemical meningitis after intrathecal baclofen injections by lumbar puncture. These cases presented with febrile meningeal syndromes during the 24 h following intrathecal baclofen injection. Direct cerebrospinal fluid (CSF) examination and CSF cultures were negative. An intense cellular reaction was observed with a marked predominance of neutrophils. Meningitis resolved spontaneously over 3-4 days. Chemical meningitis is a rare complication of intrathecal baclofen injections that must be recognized. It is a diagnosis of exclusion and its pathophysiological mechanism remains unclear.

Does gabapentin act as an agonist at native GABA(B) receptors?

Gabapentin, a novel anticonvulsant and analgesic, is a gamma-aminobutyric acid (GABA) analogue but was shown initially to have little affinity at GABA(A) or GABA(B) receptors. It was recently reported to be a selective agonist at GABA(B) receptors containing GABA(B1a)-GABA(B2) heterodimers, although several subsequent studies disproved that conclusion. In the present study, we examined whether gabapentin is an agonist at native GABA(B) receptors using a rat model of postoperative pain in vivo and periaqueductal gray (PAG) slices in vitro; PAG contains GABA(B) receptors, and their activation results in antinociception. An intrathecal injection of gabapentin or baclofen, a GABA(B) receptor agonist, induced antiallodynia in this postoperative pain model. Intrathecal injection of GABA(B) receptor antagonists CGP 35348 and CGP 55845 antagonized baclofen- but not gabapentin-induced antiallodynia. In ventrolateral PAG neurons, baclofen activated G-protein-coupled inwardly rectifying K(+) (GIRK) channels in a manner blocked by CGP 35348 or CGP 55845. However, gabapentin displayed no effect on the membrane current. In neurons unaffected by gabapentin, baclofen activated GIRK channels through GABA(B) receptors. It is concluded that gabapentin is not an agonist at GABA(B) receptors that are functional in baclofen-induced antiallodynia in the postoperative pain model in vivo and in GIRK channel activation in ventrolateral PAG neurons in vitro.