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Quinn Hogan

Publications and source records attributed to Quinn Hogan.

9 recordsLinked to original sources
PubMed2004

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. Perforated patches were allowed to take place spontaneously. The percentage loss of I(Ca) per min (within the first 20 min) was significantly less after beta-escin (0.0518%) (n = 18), versus either amphotericin (1.82%) (n = 12) or standard patch (4.52%) (n = 7), (P < 0.001). The slope of the rundown after linear fit was also less after beta-escin (P < 0.001). Minimal "steady-state" access resistance (R(a)) of 6.6 +/- 1.6 MOmega was achieved within 7.1 +/- 9.3 min following perforation with beta-escin, 7.9 +/- 3.5 MOmega within 44 =/- 14 min after amphotericin B, and 6.8 +/- 1.9 MOmega with standard patch (P < 0.05 for R(a), and P < 0.01 for permeabilization time, respectively). Success rates were 59% with beta-escin versus 27% with amphotericin. Leak >10% of peak I(Ca) was present in 25% of cells after beta-escin versus 20% after amphotericin, and 12% after standard technique. Perforated patches using beta-escin were stable for 15-60 min. We conclude that beta-escin may be used as an alternative ionophore for perforated patch-clamp studies in neurons, and results in minimal rundown that can facilitate long-term recordings of I(Ca). Limited rundown may be due to better preservation of cytosolic ATP content.

Afferent Pathways↗
PubMed2004

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). RESULTS: Substantial variance was evident in all sensory tests at baseline. After surgery, tests using brush, cold, or heat stimulation showed minimal distinctions between surgical groups. Postsurgical thresholds for flexion withdrawal from mechanical stimulation with von Frey fibers were decreased bilaterally in SNL and sham groups. In contrast, the probability of a complex hyperalgesia-type response with prolonged elevation, shaking, or licking of the paw was selectively increased on the ipsilateral side in the SNL group. Nonetheless, the effect of SNL on behavior was inconsistent, regardless of the sensory test. The behavioral measure that best distinguishes between SNL and sham groups and thereby best identifies animals with successful SNL-induced neuropathic pain is increased ipsilateral postsurgical probability of a hyperalgesia-type response to noxious mechanical stimulation. Using receiver operating characteristics analysis, mechanical hyperalgesia identifies a local SNL effect in approximately 60% of animals when specificity is required to be 90% or higher. CONCLUSIONS: Simple withdrawal from von Frey tactile stimulation, although frequently used, is not a valid measure of peripheral nerve injury pain in rats, whereas a complex hyperalgesic-type response is a specific neuropathy-induced behavior.

Animals↗
PubMed2003

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. Outward current in cells from rats with peripheral nerve injury was not sensitive to modulators of K(ATP) channels. Gabapentin, a putative K(ATP) channel opener, had minimal effect on currents in either group of neurons. We conclude that normal primary afferent neurons express K(ATP) channels that conduct current which is eliminated by peripheral nerve injury. Gabapentin does not affect this current significantly.

ATP-Binding Cassette Transporters↗
PubMed2002

The analgesic effect of gabapentin and mexiletine after breast surgery for cancer.

UNLABELLED: We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients. They were randomized to receive, in a double-blinded manner, mexiletine 600 mg/d, gabapentin 1200 mg/d, or placebo for 10 days. Anesthesia was standardized, and all patients had access to routine postoperative analgesics on demand. The visual analog scale score assessed pain at rest and after movement. Three months later, all patients were interviewed to identify intensity of chronic pain and analgesic requirements. Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50% (P = 0.029; P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons, respectively). Total paracetamol consumption was also reduced during the same time (P = 0.0085; P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control, respectively). Pain at rest and after movement was reduced by both drugs on the third postoperative day. Pain after movement also was reduced by gabapentin between the second and fifth postoperative day. Three months later, the incidence of chronic pain, its intensity, and need for analgesics were not affected by either treatment. However, burning pain was more frequent in the control group (P = 0.033). IMPLICATIONS: Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.

Acetates↗
PubMed1991

Epidural opiates and local anesthetics for the management of cancer pain.

The role of epidural morphine in chronic cancer pain treatment is unresolved. In a population of 1205 cancer patients, the aggressive use of systemic opiates limited the trial of epidural analgesia to 16 cases. Successful analgesia was achieved with epidural morphine alone in 6 of these 16 cases following systemic opiate failure. The addition of bupivacaine produced analgesia in all of the 10 remaining cases and was successful chronically in 6 cases. Complications occurred in 11 of the 16 cases of epidural analgesia and included dislodged or broken catheters, pain on injection, hyperesthesia from epidural morphine and bleeding or infection related to the epidural catheter. Epidural morphine is indicated only in selected cancer pain patients and, although bupivacaine extends the efficacy of epidural analgesia, these methods are accompanied by problems and limitations.

Adult↗
PubMedDate not supplied

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. METHODS: Male rats were prepared according to the chronic constriction injury (CCI) model. The L4 and L5 dorsal root ganglia of those selected as CCI or control after appropriate behavioral testing were removed, and neurons were enzymatically dissociated. Fluorescent dye (DiI) placed at the injury site allowed identification of neurons projecting to that site. These were acutely studied using whole-cell, perforated (with beta-escin) patch-clamp recordings. Additionally, neurons from sham or nonoperated rats were also studied. RESULTS: Although there was marked variability among cells, concentrations of GBP ranging from 0.1 to 300 micromol/L decreased neuronal peak ICa in midsized neurons (30 to 40 microm) of both sham and neuropathic rats, in a fast, reversible, and concentration-dependent manner. Intergroup differences were not significant, however the concentration-response EC50s were 2.7 micromol/L for the sham and 16.5 micromol/L for the CCI neurons. The drug suppressed I(Ca) in nonoperated rats to a lesser degree, but changes did not differ significantly from the operated groups. Calcium currents in either small or large diameter neurons were also variably decreased by 10 micromol/L of GBP in sham and CCI neurons. Current inhibition by GBP was partly voltage dependent. CONCLUSIONS: GBP, at clinically relevant concentrations, results in significant reduction of I(Ca) in both sham and neuropathic neurons, while in nonoperated rats reduced I(Ca) to a smaller degree. Sensitivity to drug was not affected by neuropathy. This current inhibition is partly voltage dependent. Depression of I(Ca) may be partly related to the binding of the drug to the alpha(2)delta modulatory subunit of the voltage activated calcium channels (VACC). Analgesia may be due to diminished release of neurotransmitter by sensory neurons, a Ca(2+)-dependent process.

Acetates↗
PubMedDate not supplied

Distribution of solution in the epidural space: examination by cryomicrotome section.

BACKGROUND AND OBJECTIVES: The routes of distribution and barriers to flow of solutions in the epidural space are incompletely determined. This study examined macroscopic details of epidural injectate spread in postmortem humans by cryomicrotome imaging. METHODS: Soon after death, 3 nonembalmed adult human subjects were injected with ink through epidural catheters inserted by standard techniques. Following freezing, microtome sectioning was performed to reveal anatomic features down to 100 microm. To control for effects of death, an adult baboon was injected during general anesthesia and subsequently examined in the same fashion. RESULTS: Injected ink was readily evident and showed spread as rivulets through numerous small channels rather than as a unified advancing front. The fascia that extends laterally from the posterior longitudinal ligament is an important barrier restricting solution flow. Solution preferentially traveled along the nerve root sheath through the intervertebral foramen. CONCLUSIONS: Distribution of solution in the epidural space is nonuniform. Rather than a uniform advancing front, spread is directed among paths between structures according to pressures by which they are compressed. No structural barriers block flow through the intervertebral foramina or spinal canal other than the fascia of the posterior longitudinal ligament.

Adult↗
PubMedDate not supplied

Animal pain models.

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Animals↗