Calcium signaling in intact dorsal root ganglia: new observations and the effect of injury.

Background: Ca is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca recording techniques use high K or field stimulation and dissociated neurons.

Depletion of calcium stores in injured sensory neurons: anatomic and functional correlates.

Background: Painful nerve injury leads to disrupted Ca signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This study examines potential causes and functional consequences of Ca store limitation after injury.

Methods: Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals.

Perioperative genomic profiles using structure-specific oligonucleotide probes.

Objectives: Many complications in the perioperative interval are associated with genetic susceptibilities that may be unknown in advance of surgery and anesthesia, including drug toxicity and inefficacy, thrombosis, prolonged neuromuscular blockade, organ failure and sepsis. The aims of this study were to design and validate the first genetic testing platform and panel designed for use in perioperative care, to establish allele frequencies in a target population, and to determine the number of mutant alleles per patient undergoing surgery. DESIGN/SETTING/PARTICIPANTS AND METHODS: One hundred fifty patients at Marshfield Clinic, Marshfield, Wisconsin, 100 patients at the Medical College of Wisconsin Zablocki Veteran's Administration Medical Center, Milwaukee, Wisconsin, and 200 patients at the University of Wisconsin Hospitals and Clinics, Madison, Wisconsin undergoing surgery and anesthesia were tested for 48 polymorphisms in 22 genes including ABC, BChE, ACE, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, beta2AR, TPMT, F2, F5, F7, MTHFR, TNFalpha, TNFbeta, CCR5, ApoE, HBB, MYH7, ABO and Gender (PRKY, PFKFB1).

Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons.

Background: We have previously shown that a decrease of inward Ca(2+) flux (I(Ca)) across the sensory neuron plasmalemma, such as happens after axotomy, increases neuronal excitability. From this, we predicted that increasing I(Ca) in injured neurons should correct their hyperexcitability.

Methods: The influence of increased or decreased I(Ca) upon membrane biophysical variables and excitability was determined during recording from A-type neurons in nondissociated dorsal root ganglia after spinal nerve ligation using an intracellular recording technique.

Modulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons.

Background: Chronic neuropathic pain resulting from neuronal damage remains difficult to treat, in part, because of incomplete understanding of underlying cellular mechanisms. We have previously shown that inward Ca2+ flux (I(Ca)) across the sensory neuron plasmalemma is decreased in a rodent model of chronic neuropathic pain, but the direct consequence of this loss of I(Ca) on function of the sensory neuron has not been defined. We therefore examined the extent to which altered membrane properties after nerve injury, especially increased excitability that may contribute to chronic pain, are attributable to diminished Ca2+ entry.

Hyperpolarization-activated current (I(h)) contributes to excitability of primary sensory neurons in rats.

In various excitable tissues, the hyperpolarization-activated, cyclic nucleotide-gated current (I(h)) contributes to burst firing by depolarizing the membrane after a period of hyperpolarization. Alternatively, conductance through open channels I(h) channels of the resting membrane may impede excitability. Since primary sensory neurons of the dorsal root ganglion show both loss of I(h) and elevated excitability after peripheral axonal injury, we examined the contribution of I(h) to excitability of these neurons.