Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior.

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .

Idiopathic pulmonary fibrosis: the role of the pharmacy benefit manager in providing access to effective, high-value care.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause that primarily affects individuals aged 60 and older. The economic costs of the disease are significant, with patients twice as likely to be hospitalized and twice as likely to require outpatient medical care as compared with those without IPF, resulting in an additional annual cost to the Medicare system of $1 billion. The first pharmacologic treatments for IPF, nintedanib and pirfenidone, were approved in 2014 for conditional use.

Biorecognition by DNA oligonucleotides after exposure to photoresists and resist removers.

Combining biological molecules with integrated circuit technology is of considerable interest for next generation sensors and biomedical devices. Current lithographic microfabrication methods, however, were developed for compatibility with silicon technology rather than bioorganic molecules, and consequently it cannot be assumed that biomolecules will remain attached and intact during on-chip processing. Here, we evaluate the effects of three common photoresists (Microposit S1800 series, PMGI SF6, and Megaposit SPR 3012) and two photoresist removers (acetone and 1165 remover) on the ability of surface-immobilized DNA oligonucleotides to selectively recognize their reverse-complementary sequence.

Herpes simplex virus vector-mediated expression of interleukin-10 reduces below-level central neuropathic pain after spinal cord injury.

Background: Neuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury.

Objective: The aim of this study was to examine the role of neuroimmune activation in below-level neuropathic pain after traumatic spinal cord injury (SCI).

Methods: Right hemilateral SCI was created in male Sprague-Dawley rats by controlled blunt impact through a T12 laminectomy.

Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons.

Patients with central pain (CP) typically have chronic pain within an area of reduced pain and temperature sensation, suggesting an impairment of endogenous pain modulation mechanisms. We tested the hypothesis that some brain structures normally activated by cutaneous heat stimulation would be hyperresponsive among patients with CP but not among patients with a central nervous system lesion causing a loss of heat or nociceptive sensation with no pain (NP). We used H(2)(15)O positron emission tomography to measure, in 15 healthy control participants, 10 NP patients, and 10 CP patients, increases in regional cerebral blood flow among volumes of interest (VOI) from the resting (no stimulus) condition during bilateral contact heat stimulation at heat detection, heat pain threshold, and heat pain tolerance levels.

Programmed assembly of DNA-coated nanowire devices.

Combining biomolecular function with integrated circuit technology could usher in a new era of biologically enabled electronics. A key challenge has been coupling different molecular functions to specific chip locations for communication with the circuit. We used spatially confined electric fields to assemble different populations of DNA-coated nanowires to desired positions with an accuracy that enabled postassembly fabrication of contacts to each individual nanowire, with high yield and without loss of DNA function.

Electrofluidic Positioning of Biofunctionalized Nanowires.

We functionalized nanowires with three different probe peptide nucleic acid (PNA) sequences, and assembled the three populations onto a lithographically patterned chip. Electrofluidic assembly enabled positioning each set of nanowires to span a different pair of guiding electrodes. Fluorescence imaging was used to probe whether the PNA on the individual nanowires remained able to selectively bind complementary DNA targets following assembly and integration of the positioned nanowires onto the chip surface.

Nanowire sensors for multiplexed detection of biomolecules.

Nanowire-based detection strategies provide promising new routes to bioanalysis that could one day revolutionize the healthcare industry. This review covers recent developments in nanowire sensors for multiplexed detection of biomolecules such as nucleic acids and proteins. We focus on encoded nanowire suspension arrays and semiconductor nanowire-based field-effect transistors.

Bottom-up assembly of large-area nanowire resonator arrays.

Directed-assembly of nanowire-based devices will enable the development of integrated circuits with new functions that extend well beyond mainstream digital logic. For example, nanoelectromechanical resonators are very attractive for chip-based sensor arrays because of their potential for ultrasensitive mass detection. In this letter, we introduce a new bottom-up assembly method to fabricate large-area nanoelectromechanical arrays each having over 2,000 single-nanowire resonators.

Animal models of painful diabetic neuropathy: the STZ rat model.

Painful peripheral neuropathy is a common secondary complication of diabetes. The streptozotocin (STZ)-induced diabetic rat is the most commonly employed animal model used to study mechanisms of painful diabetic neuropathy and to evaluate potential therapies. A low dose STZ protocol is described for inducing experimental diabetes in the rat.

Concurrent activation of the somatosensory forebrain and deactivation of periaqueductal gray associated with diabetes-induced neuropathic pain.

We combined behavioral testing with brain imaging using (99m)Tc-HMPAO (Amersham Health) to identify CNS structures reflecting alterations in pain perception in the streptozotocin (STZ) model of type I diabetes. We induced diabetic hyperglycemia (blood glucose >300 mg/dl) by injecting male Sprague-Dawley rats with STZ (45 mg/kg i.p.

The costs and consequences of multiple sclerosis relapses: a managed care perspective.

One of the more common "rare diseases," multiple sclerosis (MS) offers a prototype to managed care for a unique and cost-effective model to better manage the outcomes of this dreaded disease. Using a specialty pharmacy model, the application of traditional disease management processes, including monthly contact, selected clinical assessments combined with targeted interventions, and data collection and analysis, hold the promise to significantly lower the relapse rate and disability progression for patients with MS. At the same time, savings in both direct and indirect costs should occur.

In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion.

Compensatory changes following disruption of neuronal circuitry have been indicated by previous imaging studies of stroke and other brain injury, but evidence of the pathways involved in such dynamic changes has not been shown in vivo. We imaged rats before and after lesion-induced disruption of the lateral olfactory tract to investigate the subsequent recovery and/or reorganization of functional neuronal circuitry. Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+).

Clonidine effects on pain evoked SII activity in humans.

We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi-channel magnetoencephalography (MEG). Pain was elicited by electrical shocks applied intracutaneously to the fingertip. Subjects rated pain intensity and perceptions of tiredness and passiveness by numerical ranking scales.

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury.

Forebrain activation patterns in normal and spinal-injured Sprague-Dawley (SD) rats were determined by measuring regional cerebral blood flow as an indicator of neuronal activity. Data are compared to our previously published findings from normal and spinal-injured Long-Evans (LE) rats and reveal a striking degree of overlap, as well as differences, between strains in the basal (unstimulated) forebrain activation in normal animals. Specifically, 81% of the structures sampled showed similar activation in both strains, suggesting a consistent and identifiable pattern of basal cerebral activation in the rat.

Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat.

Diabetic neuropathy is a common form of peripheral neuropathy, yet the mechanisms responsible for pain in this disease are poorly understood. Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy. We investigated the expression and function of TTX-sensitive (TTX-S) and TTX-R sodium channels in dorsal root ganglion (DRG) neurons and the responses to thermal hyperalgesia and mechanical allodynia in streptozotocin-treated rats between 4-8 weeks after onset of diabetes.

Designing and implementing an effective specialty pharmacy service program.

The universe of high-tech biologic medications is expanding rapidly, and health plans are struggling to control the rising costs associated with the use of these agents. Specialty pharmaceutical networks are gaining greater visibility as a helpful tool in this effort. The author describes how to write the request for proposal and begin the decision-making and implementation processes for specialty pharmacy services.

Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma.

Background: Current literature suggests that anemia at baseline is an important adverse prognostic factor for lymphoma-related outcomes. We evaluated the prevalence, risk factors, and prognostic value of anemia in patients with intermediate-grade non-Hodgkin's lymphoma (IGNHL) treated in a community-based practice.

Methods: The retrospective sample included 591 patients who had IGNHL diagnosed between 1993 and 1999 and who were subsequently treated with CHOP chemotherapy.

A unique representation of heat allodynia in the human brain.

Skin inflammation causes innocuous heat to become painful. This condition, called heat allodynia, is a common feature of pathological pain states. Here, we show that heat allodynia is functionally and neuroanatomically distinct from normal heat pain.

Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat.

We identified long-term (up to 12 weeks), bilateral changes in spontaneous and evoked pain behavior and baseline forebrain activity following a chronic constriction injury (CCI) of the sciatic nerve. The long-term changes in basal forebrain activation following CCI were region-specific and can be divided into forebrain structures that showed either: (1) no change, (2) an increase, or (3) a decrease in activity with regard to the short-term (2 weeks) changes we previously reported. All the rats showed spontaneous pain behaviors that persisted throughout the 12-week observation period, resembling the pattern of change found in four limbic system structures: the anterior dorsal thalamus, habenular complex, and the cingulate and retrosplenial cortices.

Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat.

Lesions in the cingulate cortex have attenuated pain-related behavior in humans. We wished to evaluate an animal model of this effect by studying the effects of bilateral lesions within the medial frontal cortex, including rat cingulate cortex, on performance in 3 behavioral tests: the formalin, hot-plate, and tail-flick tests. Average hot-plate latencies, but not formalin test scores or tail-flick latencies, were significantly increased by an average of 82% in rats with medial frontal cortex lesions, as compared to sham-operated control rats.

Central delay of the laser-activated rat tail-flick reflex.

The latency of the heat-activated rat tail-flick (TF) reflex is dependent upon 4 variables, none of which has previously been determined: activation of cutaneous nociceptors (TN); afferent conduction to the dorsal horn (TA); conduction within the central nervous system (CNS) (central delay); and conduction from the ventral horn (VH) to, and activation of, tail muscles (TE). Using a CO2 infrared laser (10 W, 45 msec) to produce synchronous activation of tail-skin nociceptors, TF latency (EMG response) was measured in 10 awake rats. Based on shifts in response latency from points of stimulation near the tip and base of the tail, conduction velocity in the afferent limb of the reflex was estimated to be 0.

Cutaneous pain and detection thresholds to short CO2 laser pulses in humans: evidence on afferent mechanisms and the influence of varying stimulus conditions.

Pain and detection thresholds to short CO2 laser pulses were studied in healthy human subjects. Pain thresholds were significantly higher than detection thresholds in both hairy and glabrous skin; in the glabrous skin both thresholds were higher in the hairy skin. The range from detection threshold to pain threshold was larger in the glabrous skin.

Responses of single cutaneous fibers to noxious thermal pulse stimulation of cat upper hind limb.

Previous experiments have shown that cats respond to noxious thermal pulse stimulation of the upper hind limb at an average latency of 2.3 sec. To determine if C fiber afferents could mediate this response, we recorded the response latency and threshold of single fibers of cat femoral cutaneous nerve to the same stimuli used in the behavioral experiments.