Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.

Cannabinoid type 1 receptors (CB1Rs) orchestrate brain reward circuitry and are prevalent neurobiological targets for endocannabinoids and cannabis in the mammalian brain. Decades of histological and electrophysiological studies have established CB1R as presynaptic G-protein coupled receptors (GPCRs) that inhibit neurotransmitter release through retrograde signaling mechanisms. Recent seminal work demonstrates CB1R expression on astrocytes and the pivotal function of glial cells in endocannabinoid-mediated modulation of neuron-astrocyte signaling. Here, we review key facets of CB1R-mediated astroglia regulation of synaptic glutamate transmission in the nucleus accumbens with a specific emphasis on cocaine-directed behaviors.

Long-term tolerability of capnography and respiratory inductance plethysmography for respiratory monitoring in pediatric patients treated with patient-controlled analgesia.

BACKGROUND: The Anesthesia Patient Safety Foundation has advocated the use of continuous electronic monitoring of oxygenation and ventilation to preemptively identify opioid-induced respiratory depression. In adults, capnography is the gold standard in respiratory monitoring. An alternative technique used in sleep laboratories is respiratory inductance plethysmography (RIP). However, it is not known if either monitor is well tolerated by pediatric patients for prolonged periods of time. AIM: The goal of this study was to determine whether capnography or RIP is better tolerated in nonintubated, spontaneously breathing pediatric patients being treated with intravenous patient-controlled analgesia (IVPCA). METHODS: Nasal cannula capnography with oral sampling and thoracic and abdominal inductance plethysmography bands were placed along with the routine monitors on pediatric patients being treated for acute pain with IVPCA. Study monitors were left in place for as long as they were tolerated by the patient, up to a maximum of 24 consecutive hours. If the patient did not wear a particular study monitor for any reason, but tolerated the remaining monitor, participation in the study continued. If the patient would not wear either monitor, participation was terminated. RESULTS: Twenty-six patients (18 female, eight male, average age 10.1 ± 5.5 years) consented to participate, but only 14 patients attempted to wear one or both the devices. Among those who wore either device, median time to device removal was 8.33 h (range 0.3-23.6 h) for capnography and 23.5 h (range 0.7-24 h) for RIP bands. CONCLUSION: Children did not tolerate wearing capnography cannulae for prolonged periods of time, limiting the usefulness of this device as a continuous monitor of ventilation in children. RIP bands were better tolerated; however, they require further assessment of their utility. Until more effective, child-friendly monitors are developed and their utility is validated, guidelines recommended for adult patients cannot be extended to children.

Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1.

Transient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. Pirt is expressed in most nociceptive neurons in the dorsal root ganglia (DRG) including TRPV1-positive cells. Pirt null mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in Pirt-deficient DRG neurons are significantly attenuated. Heterologous expression of Pirt strongly enhances TRPV1-mediated currents. Furthermore, the C terminus of Pirt binds to TRPV1 and several phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), and can potentiate TRPV1. The PIP2 binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.