Discover the most talked about and latest scientific content & concepts.

Concept: Intrathecal


TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1(-/-) mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, activate mouse and human TRPA1. These metabolites also activate native TRPA1 and, as a consequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons. The N-acetyl-p-benzoquinoneimine metabolite L-cysteinyl-S-acetaminophen was detected in the mouse spinal cord after systemic acetaminophen administration. In the hot-plate test, intrathecal administration of N-acetyl-p-benzoquinoneimine, p-benzoquinone and the electrophilic TRPA1 activator cinnamaldehyde produced antinociception that was lost in Trpa1(-/-) mice. Intrathecal injection of a non-electrophilic cannabinoid, Δ(9)-tetrahydrocannabiorcol, also produced TRPA1-dependent antinociception in this test. Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain.

Concepts: Neuron, Pain, Sensory system, Paracetamol, Rat, Rodent, Mouse, Intrathecal


BACKGROUND:: Intrathecal baclofen (ITB) is an effective therapy for spasticity and dystonia in pediatric populations; however, there are associated infectious complications. METHODS:: Patients who had an initial ITB device implanted at our center were followed to determine the proportion of patients with infectious and non-infectious complications, identify risk factors for infection and describe the clinical presentations, treatment and outcomes of infectious complications. RESULTS:: Over the 15 year study period, 139 patients had an initial ITB device placed. The mean age at placement was 13.6 years (range- 6 months to 41 years). In the first year of follow-up, 83% had no complications or secondary procedures, 17% had at least one secondary procedure and 5% had an infectious complication. The median time until infection was 14 days (mean 33 ± 42 days). Patients with secondary spasticity or dystonia were more likely to have infections than patients with cerebral palsy (86% vs.14%; p<0.0001). In the 94 patients with a first secondary procedure, 29% had at least one other procedure and 8% had an infection in the one year follow-up. Overall, 24 patients had 27 infections; 22% superficial, 33% deep and 45% organ space. Staphylococcus aureus was isolated in 50% of those with cultures obtained. Explantation was required in 59% of patients with an infection and differed by infection type: superficial (17%), deep (44%) and organ space (92%) (p=0.004). CONCLUSIONS:: Infectious complications were relatively uncommon; however, when present, frequently led to the explantation of the ITB pump device.

Concepts: Staphylococcus aureus, Infection, Median, Transmission and infection of H5N1, Intrathecal, Spastic diplegia, Intrathecal pump, Baclofen


Dexmedetomidine, a selective alpha 2-adrenoceptor (α2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the α2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.

Concepts: Present, Molecular biology, Signal transduction, Effect, Pain, Agonist, Intrathecal, Functional selectivity


BACKGROUND:The epidural test dose, used to identify unintended intrathecal placement, should reliably produce a spinal block without posing a threat to the patient. Most anesthesiologists administer a dose of local anesthetic, commonly lidocaine 45 mg. Pregnant patients are more sensitive to local anesthetics; high and total spinal anesthesia have been reported in the pregnant population with this dose. We hypothesized that lidocaine 30 mg was as effective as lidocaine 45 mg in creating rapid objective evidence of a sensory or motor block.METHODS:In this prospective, randomized, double-blind trial, patients scheduled for cesarean delivery were assigned to 1 of 4 groups: lidocaine 30 mg in the spinal or epidural space, or lidocaine 45 mg by the same routes. A blinded observer assessed the degree of sensory and motor block. The ability to identify intrathecal injection of each dose was compared. Sensory block above T6 dermatome and hypotension were recorded as side effects.RESULTS:Intrathecal administration of lidocaine 30 mg produced rapid subjective and objective signs of neuroblockade within 3 minutes (100%, 95% confidence interval CI, 85%-100% for each). Lidocaine 45 mg produced similar results. All patients in both groups described their legs as warm or heavy after 3 minutes and had a motor block by 5 minutes. On the basis of an intrathecal catheter rate of 1:380, the observed negative predictive value for intrathecal placement if the patient described no sensory changes at 3 minutes was 100% (95% CI, 99.95%-100%) for 30 mg and 100% (95% CI, 99.93%-100%) for 45 mg. We did not identify a decrease in the rate of side effects with the lower dose.CONCLUSIONS:Our results suggest that there is unlikely to be a large difference in the ability of these doses to detect unintentional intrathecal catheter placement. While the negative predictive value for intrathecal injection is very high for both doses, the 95% CI for the sensitivity of either dose is too wide to demonstrate clinical safety to identify all intrathecal catheters. A much larger study is warranted to assess whether there is a lower sensitivity with the 30-mg dose, or a propensity toward high cephalad motor block levels with the 45-mg dose.

Concepts: Childbirth, Randomized controlled trial, Anesthesia, Epidural, Catheter, Intrathecal, Local anesthetic, Spinal anaesthesia


Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor-bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs.

Concepts: Pain management, Intrathecal


BACKGROUND: Shivering during regional anesthesia is a common complication and is related to a decrease in the patient’s core body temperature. Previous studies have shown that acupuncture on specific acupoints can preserve core body temperature. The present study evaluated the effect of electroacupuncture in preventing the shivering caused by regional anesthesia. METHODS: This prospective and randomized controlled study analyzed the data from 80 patients undergoing urological surgery, who were classified as ASA I or II. Spinal anesthesia was performed in all patients using 15 mg of bupivacaine. The patients were randomly allocated to receive either placebo acupuncture (Group P, n = 40) or electroacupuncture (Group A, n = 40) for 30 min before administration of spinal anesthesia. Shivering score was recorded at 5 min intervals, with 0 representing no shivering and 4 representing the most severe shivering possible. Heart rate, blood pressure, and tympanic temperature were recorded before the intrathecal injection, and again every 5 min thereafter until 30 min. RESULTS: After spinal anesthesia, the decrease in tympanic temperature was less for Group A patients than Group P, with the difference being statistically significant. After 15 min, 13 patients in Group P attained a shivering score of 3 or more, compared with 3 patients in Group A. Significantly more patients in Group P attained a shivering score of at least 1. CONCLUSIONS: The prophylactic use of electroacupuncture might maintain core body temperature, and may effectively prevent the shivering that commonly develops during regional anesthesia.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12612000096853.

Concepts: Clinical trial, Randomized controlled trial, Statistical significance, Pharmaceutical industry, Clinical research, Acupuncture, Intrathecal, Spinal anaesthesia


Intrathecal analgesia is more effective than conservative delivery methods such as drugs administered orally or intravenously. Programmable devices such as Medtronic’s SynchroMed systems have often been applied for long-term intrathecal analgesia. However, the totally implanted systems are very expensive in China. Considering cost-effectiveness, a reliable transmission protocol for a ZigBee-Based wireless analgesia pump system was used for long-term intrathecal analgesia in the home care of patients.

Concepts: Health economics, Intrathecal, Data transmission, Patient-controlled analgesia


Clinical studies suggest that descending inhibitory controls from the brainstem are important for speeding recovery from pain following surgery. We examined the effects of destroying spinally projecting noradrenergic neurons via intrathecally administered antibody to dopamine β-hydroxylase conjugated to saporin (DβH-saporin) on recovery in an acute incisional pain model. Mechanical and thermal paw withdrawal thresholds and non-evoked spontaneous guarding scores were tested for several weeks postoperatively and analyzed using mixed effects growth curve modeling. DβH-saporin treatment resulted in a significant prolongation in the duration of mechanical and to a lesser degree thermal hypersensitivity in the ipsilateral paw of incised rats but did not increase the duration of spontaneous guarding. DβH-saporin treatment was also associated with increased microglial and astrocyte activation in the ipsilateral spinal cord 21 days post-incision compared to IgG-saporin treated controls. Chronic intrathecal administration of the α2 adrenergic receptor antagonist atipamezole (50-200 μg/day) produced similar effects. These data suggest that spinally projecting noradrenergic pathways and spinal α2 adrenergic receptor activation are important for speeding recovery from hypersensitivity following surgical incision possibly by reducing spinal glial activation. Interventions that augment the noradrenergic system may be important to speed recovery from pain after surgery.

Concepts: Neuron, Receptor, Neurotransmitter, Agonist, Rat, Norepinephrine, Intrathecal, Adrenergic receptor


OBJECT Intrathecal baclofen (ITB) is an effective management option for childhood hypertonia. Given the potential complications of implanted ITB pumps, trials of ITB are usually performed as part of the workup for ITB pumps. Two methods are used for ITB trials, lumbar puncture (LP) and catheter insertion into the intrathecal space. Little has been written to date on the number of positive trials and complications in trials. This study aimed to report the outcomes and complications in ITB trials for childhood hypertonia (dystonia, spastic, or mixed). METHODS A retrospective case notes review was conducted of all patients who underwent ITB trials at the Evelina London Children’s Hospital between 2005 and 2012 (inclusive). Positive trials were defined as a reduction in Modified Ashworth Scale by a minimum of 1 point in at least 2 muscle groups and improvement reported by the caregivers in the areas of goals agreed upon between professionals and the families. RESULTS Our patient group comprised children with dystonia (n = 7), mixed spasticity/dystonia (n = 29), spasticity (n = 4), and pain (n = 1). A total of 47 trials were attempted in 41 children. Forty trials were successfully completed, with 39 being positive. Thirty-three were catheter trials, and 14 were LPs. The overall complication rate in the 47 attempted trials was 53%: 61% in catheter trials, and 36% in LP trials. This difference was not statistically significant. The most common complications were vomiting (n = 9) and CSF leak (n = 4). The most serious complication was meningitis (n = 1) in a catheter trial. No patients experienced a permanent injury. CONCLUSIONS There is a high risk of minor self-limiting complications with ITB trials, which needs to be factored into the decision process of progression to trials. The rate of positive trials in this study was 98%, of which 21% did not progress to pump implantation. While the authors would still advocate for ITB trials prior to ITB pump insertion to aid parental decision-making, this figure suggests that with good patient selection, ITB pumps could be placed without a preceding trial.

Concepts: Decision making, Muscle, Cerebrospinal fluid, Intrathecal, Spastic diplegia, Lumbar puncture, Spasticity, Baclofen


The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0weeks) and chronic (at 4weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration.

Concepts: Spinal cord, Cellular differentiation, Injury, Spinal cord injury, Physical trauma, Intrathecal, Sonic hedgehog, Damage