Strain differences in cortical electroencephalogram associated with isoflurane-induced loss of consciousness.

Introduction: Previously observed increased sensitivity to noxious stimulation in the Dahl salt-sensitive rat strain (SS/JrHsdMcwi, abbreviated as SS) compared to Brown Norway rats (BN/NhsdMcwi abbreviated as BN) is mediated by genes on a single chromosome. The current study used behavioral and electrocortical data to determine if differences also exist between SS and BN rats in loss of consciousness.

Methods: Behavioral responses, including loss of righting, (a putative index of consciousness) and concurrent electroencephalogram recordings, in 12 SS and BN rats were measured during isoflurane at inhaled concentrations of 0, 0.

Ca²⁺-dependent regulation of Ca²⁺ currents in rat primary afferent neurons: role of CaMKII and the effect of injury.

Currents through voltage-gated Ca²⁺ channels (I(Ca)) may be regulated by cytoplasmic Ca²⁺ levels ([Ca²⁺](c)), producing Ca²⁺-dependent inactivation (CDI) or facilitation (CDF). Since I(Ca) regulates sensory neuron excitability, altered CDI or CDF could contribute to pain generation after peripheral nerve injury. We explored this by manipulating [Ca²⁺](c) while recording I(Ca) in rat sensory neurons.

Quantification of gene expression after painful nerve injury: validation of optimal reference genes.

Stably expressed housekeeping genes (HKGs) are necessary for standardization of transcript measurement by quantitative real-time polymerase chain reaction (qRT-PCR). Peripheral nerve injury disrupts expression of numerous genes in sensory neurons, but the stability of conventional HKGs has not been tested in this context. We examined the stability of candidate HKGs during nerve injury, including the commonly used 18S ribosomal RNA, β-tubulin I and β-tubulin III, actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and hypoxanthine phosphoribosyltransferase 1 (HPRT1), and mitogen-activated protein kinase 6 (MAPK6).

Norepinephrine infusion into nucleus basalis elicits microarousal in desflurane-anesthetized rats.

Background: The nucleus basalis of Meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. Its role in the modulation of general anesthesia was investigated.

Methods: Rats were chronically implanted with bilateral infusion cannulae in the nucleus basalis of Meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices.

Acupuncture for 'frequent attenders' with medically unexplained symptoms: a randomised controlled trial (CACTUS study).

Background: Medically unexplained physical symptoms (MUPS) are common and difficult to treat.

Aim: To investigate the effectiveness of adding five-element acupuncture to usual care in 'frequent attenders' with MUPS.

Design And Setting: Randomised controlled trial in four London general practices.

KATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy.

Background: ATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the KATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy.

Results: PCR demonstrated Kir6.

Suppressed Ca2+/CaM/CaMKII-dependent K(ATP) channel activity in primary afferent neurons mediates hyperalgesia after axotomy.

Painful axotomy decreases K(ATP) channel current (IK(ATP)) in primary afferent neurons. Because cytosolic Ca(2+) signaling is depressed in injured dorsal root ganglia (DRG) neurons, we investigated whether Ca(2+)-calmodulin (CaM)-Ca(2+)/CaM-dependent kinase II (CaMKII) regulates IK(ATP) in large DRG neurons. Immunohistochemistry identified the presence of K(ATP) channel subunits SUR1, SUR2, and Kir6.

Nitric oxide activates ATP-sensitive potassium channels in mammalian sensory neurons: action by direct S-nitrosylation.

Background: ATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain.

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons.

Unlabelled: Calcium-activated potassium channels regulate AHP and excitability in neurons. Since we have previously shown that axotomy decreases I(Ca) in DRG neurons, we investigated the association between I(Ca) and K((Ca)) currents in control medium-sized (30-39 microM) neurons, as well as axotomized L5 or adjacent L4 DRG neurons from hyperalgesic rats following L5 SNL. Currents in response to AP waveform voltage commands were recorded first in Tyrode's solution and sequentially after: 1) blocking Na(+) current with NMDG and TTX; 2) addition of K((Ca)) blockers with a combination of apamin 1 microM, iberiotoxin 200 nM, and clotrimazole 500 nM; 3) blocking remaining K(+) current with the addition of 4-AP, TEA-Cl, and glibenclamide; and 4) blocking I(Ca) with cadmium.

Painful peripheral nerve injury decreases calcium current in axotomized sensory neurons.

Background: Reports of Ca(2+) current I(Ca) loss after injury to peripheral sensory neurons do not discriminate between axotomized and spared neurons. The spinal nerve ligation model separates axotomized from spared neurons innervating the same site. The authors hypothesized that I(Ca) loss is a result of neuronal injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4 neurons, as well as neurons from rats undergoing skin incision alone.

Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons in rats.

Background: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage.

Beta-escin diminishes voltage-gated calcium current rundown in perforated patch-clamp recordings from rat primary afferent neurons.

Perforated patch recordings of neuronal calcium currents (I(Ca)) with amphotericin B or nystatin reduce dialysis of intracellular constituents and current rundown, but can be difficult and frequently unsuccessful. We investigated the saponin beta-escin as a putative ionophore for perforated patch I(Ca) recordings in acutely dissociated, rat dorsal root ganglion neurons. I(Ca) was recorded in time-course studies after including either beta-escin (50 microM), or amphotericin B (240 microg/ml) as perforating ionophores in the internal pipette solution, in comparison to standard ruptured-patch technique, using suction.

Detection of neuropathic pain in a rat model of peripheral nerve injury.

Background: Behavioral criteria that confirm neuropathic pain in animal injury models are undefined. Therefore, the authors sought clinically relevant measures that distinguish pain behavior of rats with peripheral nerve injury from those with sham injury.

Methods: The authors examined mechanical and thermal sensory sensitivity, comparing responses at baseline to responses after spinal nerve ligation (SNL group), sham nerve injury (sham group), or skin incision alone (control group).

ATP-sensitive potassium channels in rat primary afferent neurons: the effect of neuropathic injury and gabapentin.

ATP-sensitive potassium (K(ATP)) currents were examined in dorsal root ganglion neurons from neuropathic and control rats using whole-cell voltage clamp recordings. K(ATP) channel openers (diazoxide and pinacidil) enhanced, and the blocker glibenclamide inhibited an outward current in control neurons in a manner dependent on the pipette ATP concentration. Analysis of reversal potentials showed that this current is carried by K(+) ions.

Loss of T-type calcium current in sensory neurons of rats with neuropathic pain.

Background: Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown.

Gabapentin decreases membrane calcium currents in injured as well as in control mammalian primary afferent neurons.

Background And Objectives: Neuropathic pain following injury to peripheral sensory neurons is a common clinical problem and frequently difficult to treat. Gabapentin (GBP), a novel anticonvulsant, has significant analgesic effects in clinical neuropathic states and in relevant preclinical models, but its mechanism of action remains unclear. Because calcium currents play a significant role in neuronal function, this study was designed to assess the effect of GBP on the membrane voltage-activated inward calcium currents (I(Ca)) in dorsal root ganglia (DRG) primary afferent neurons of neuropathic versus control rats.