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Neuropathic pain is a chronic disability associated with a dysfunction of the nervous system, initiated by a primary lesion or disease. Even after resolution of the initiating pathology, neuropathic pain often persists, leading to a significantly diminished quality of life. A vast literature has documented alterations in the expression and distribution of various pain-related proteins in the peripheral nervous system following injury or disease. The current review examines pain-related molecules in the pathogenesis of peripheral nerve injury-induced pain and discusses potentially useful therapeutic targets on the basis of preclinical findings in rodent neuropathic pain models. There are indeed a number of cellular processes that are involved in maintaining the neuropathic pain state, but the current review will focus on transmembrane proteins, particularly the voltage-gated and ligand-gated ion channels, which modulate peripheral nerve function. Given the complexity of the process involved in peripheral nerves, clinical efficacy could be greatly enhanced if several of these targets are engaged at once. A key advantage of therapy directed peripherally is that penetration of the therapeutic into the CNS is not entirely necessary, thereby reducing the risk of adverse psychomotor effects. While a number of fascinating targets have been identified in preclinical rodent models, there is a need to confirm that they are in fact relevant to clinical neuropathic pain. Thus, the current review will also discuss the extent to which clinical data confirms the findings of preclinical studies.

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested that there be greater utilization of non-human primates (NHP) in preclinical pain studies. Methods to induce chronic pain-like states and quantify changes in nociception that have been developed in rodents could be adapted to the NHP. Similarly, human experimental injury-induced sensitization, which attempts to temporarily mimic the neuropathology and symptoms observed in the chronic pain state, could be adapted to the NHP. The NHP could then serve as a platform to validate human experimental models as well as proof-of-concept studies. Beyond experimentally modeled pain states, a number of naturally occurring disease states, such as osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis testing and proof-of-concept studies. While NHP studies are logistically cumbersome, it is envisioned that NHP pain models will add value to current preclinical data and greatly facilitate the discovery of novel analgesic treatments.

This study concerns twist phenomena occurring in curved hat channel products and aims to clarify the causes of twist using physical quantities obtained by finite element analysis. Several drawing heights were examined. We evaluated the torque around the longitudinal axis, which can be regarded as the driving force of the twist. In addition, transitions of the torque during the process of tool removal were analyzed. After removing the die and blank holder, the twist torque in models with larger drawing heights became negative, accounting for the positive twist, which occurs after punch and pad removal. On the other hand, the twist torque in models with smaller drawing heights remained positive, accounting for the negative twist. Such analyses of the transition of twist torque provide useful information when considering measures for reducing twist.

Si ion implantation was widely used to synthesize specimens of SiO 2 containing supersaturated Si and subsequent high temperature annealing induces the formation of embedded luminescent Si nanocrystals. In this work, the potentialities of excimer UV-light (172 nm, 7.2 eV) irradiation and rapid thermal annealing (RTA) to enhance the photoluminescence and to achieve low temperature formation of Si nanocrystals have been investigated. The Si ions were introduced at acceleration energy of 180 keV to fluence of 7.5 × 10 16 ions/cm 2 . The implanted samples were subsequently irradiated with an excimer-UV lamp. After the process, the samples were rapidly thermal annealed before furnace annealing (FA). Photoluminescence spectra were measured at various stages at the process. We found that the luminescence intensity is strongly enhanced with excimer-UV irradiation and RTA. Moreover, effective visible photoluminescence which is not observed with a simple FA treatment, is found to be observed even after FA at 900 °C, only for specimens treated with excimer-UV lamp and RTA. Based on our experimental results, we discuss the effects of excimer-UV lamp irradiation and RTA process on Si nanocrystals related photoluminescence.

Si ion implantation was widely used to synthesize specimens of SiO2 containing supersaturated Si and subsequent high temperature annealing induces the formation of embedded luminescent Si nanocrystals. In this work, the potentialities of excimer UV-light (172 nm, 7.2 eV) irradiation and rapid thermal annealing (RTA) to enhance the photoluminescence and achieve low temperature (below 1000 o C) formation of Si nanocrystals have been investigated. The Si ions were introduced at acceleration energy of 180 keV to fluence of 7.5 x 10 16 ions/cm 2 . The implanted samples were subsequently irradiated with a excimer-UV lamp. After the process, the samples were rapidly thermal annealed before furnace annealing (FA). Photoluminescence spectra were measured at various stages at the process. We found that the luminescence intensity is strongly enhanced with excimer-UV irradiation and RTA prior to conventional FA at 1050 o C. Moreover, effective visible photoluminescence is found to be observed even after FA at 900 o C, only for specimens treated with excimer-UV lamp and RTA, prior to a low temperature FA process. Based on our experimental results, we discuss the effects of excimer-UV lamp irradiation and RTA process on the luminescence.

Si ion implantation was widely used to synthesize specimens of SiO 2 containing supersaturated Si and subsequent high temperature annealing induces the formation of embedded luminescent Si nanocrystals. In this work, the potentialities of excimer UV-light (172 nm, 7.2 eV) irradiation and rapid thermal annealing (RTA) to achieve low temperature (below 1000 °C) formation of luminescent Si nanocrystals in SiO 2 have been investigated. The Si ions were introduced at acceleration energy of 180 keV to fluences of 7.5 × 10 16 and 1.5 × 10 17 ions/cm 2 . The implanted samples were subsequently irradiated with an excimer-UV lamp for 2 h. After the process, the samples were rapidly thermal annealed at 1050 °C for 5 min before furnace annealing (FA) at 900 °C. Photoluminescence spectra were measured at various stages at the process. Effective visible photoluminescence is found to be observed even after FA at 900 °C, only for specimens treated with excimer-UV lamp and RTA, prior to a low temperature FA process. Based on our experimental results, we discuss the mechanism for the initial formation process of the luminescent Si nanocrystals in SiO 2 , together with the effects with excimer lamp irradiation and RTA process on the luminescence.

We studied the growth technique for the dislocation reduction in a-plane GaN grown by metal organic chemical vapour deposition (MOCVD) using AlInN buffer layer, high temperature atomic layer epitaxy, and trenched r-sapphire technique. By using these techniques, the crystal quality was much improved. We also fabricated blue light emitting diodes (LEDs) on a-plane GaN film over r-sapphire substrate and on a-plane bulk GaN substrate. The electroluminescence (EL) characteristics of the LED samples were examined, and we found that the EL near field pattern from homo-epitaxially grown a-GaN based LED was spatially uniform, although the pattern from the LED on r-sapphire substrate was not uniform. The output power at the wavelength of 430nm was 0.72mW at the 20mA injection current for the sample on a-plane bulk GaN. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The behavior of relative intensity noise of GaInNAsSb 1300-nm-range vertical-cavity surface-emitting lasers (VCSELs) is presented for the first time. The relative intensity noise drastically increases beyond a critical optical feedback. It was theoretically and experimentally found that the increase of relaxation oscillation frequencies was effective for the sensitivity of the optical feedback in the single-mode long-wavelength VCSELs. In our experiment, the critical feedback levels were -32 and -29 dB when frequencies were 4.0 and 5.8 GHz. This result is in good agreement with a theory.

Potentialities of rapid thermal annealing to enhance the photoluminescence emission of Si nanocrystals in SiO2 have been investigated. Ion implantation was used to synthesize specimens of SiO2 containing excess Si with different concentrations. Si precipitation to form nanocrystals in implanted samples takes place with a conventional furnace anneal. The photoluminescence intensity and the peak energy of emission from Si nanocrystals depend on implanted ion fluence. Moreover, the luminescence intensity is strongly enhanced with a rapid thermal anneal prior to a conventional furnace anneal. The luminescence intensity, however, decreases with a rapid thermal anneal following a conventional furnace anneal. It is found that the order of heat treatment is an important factor in intensities of the luminescence. Moreover, the luminescence peak energy is found to be dependent, but a little, on thermal history of specimens. Based on our experimental results, we discuss about the mechanism of an enhancement of the photoluminescence, together with the mechanism of photoemission from encapsulated Si nanocrystals produced in a SiO2 matrix by ion implantation and annealing.

1.3-/spl mu/m-range GaInNAsSb vertical-cavity surface-emitting lasers (VCSELs) with the doped mirror were investigated. GaInNASb active layers that include a small amount of Sb can be easily grown in a two-dimensional manner as compared with GaInNAs due to the suppression of the formation of three-dimensional growth in MBE growth. The authors obtained the lowest J/sub th/ per well (150 A/cm/sup 2//well) for the edge-emission type lasers due to the high quality of GaInNAsSb quantum wells. Using this material for the active media, the authors accomplished the first continuous wave operation of 1.3-/spl mu/m-range GaInNAsSb VCSELs. For the reduction of the threshold voltage and the differential resistance, they used the doped mirror grown by metal-organic chemical vapor deposition (MOCVD). By three-step growth, they obtained 1.3-/spl mu/m GaInNAs-based VCSELs with the low threshold current density (3.6 kA/cm/sup 2/), the low threshold voltage (1.2 V), and the low differential resistance (60 /spl Omega/) simultaneously for the first time. The back-to-back transmission was carried out up to 5 Gb/s. Further, the uniform operation of 10-ch VCSEL array was demonstrated. The maximum output power of 1 mW was obtained at 20/spl deg/C by changing the reflectivity of the front distributed Bragg reflector mirror. GaInNAsSb VCSELs were demonstrated to be very promising material for realizing the 1.3-/spl mu/m signal light sources, and the usage of the doped mirror grown by MOCVD is the best way for 1.3-/spl mu/m VCSELs.

A possible mechanism for the photoemission from Si nanocrystals in an amorphous SiO 2 matrix fabricated by ion implantation is reported. We have measured the implantation dose dependence on the photoluminescence behavior images of Si nanocrystals in SiO 2 layers, fabricated by ion implantation and a subsequent annealing step. After annealing, a photoluminescence band, peaking just below 1.7 eV, was observed. The peak energy of the photoluminescence was found to be affected by the dose of implanted Si ions, but to be independent of annealing time. We also present experimental results of high-resolution transmission electron microscopy (HRTEM) for each annealing step. The size of Si nanocrystals increases with increasing ion dose and annealing time. These results indicate that whilst the excitation photons are absorbed by Si nanocrystals, the emission is not simply due to electron–hole recombination inside the Si nanocrystals, but is related to the presence of some kind of defects, most likely located at the interface between the Si nanocrystals and the SiO 2 , for which the characteristic energy levels are affected by cluster–cluster interactions.

Persistent sensitivity to noxious and innocuous somatic stimuli results from peripheral nerve injury. Following chronic constriction injury (CCI) of the sciatic nerve in the rat, the hind paw ipsilateral to the injury displays significantly decreased response latencies to a noxious heat stimulus (thermal hyperalgesia), compared with the contralateral uninjured paw. The ligated paw also shows increased lifting and duration of lifting from a cooled (4 +/- 1 degrees C) surface. To characterize the peripheral nerve component of increased sensitivity to cold, CCI rats were systemically injected with the potent capsaicin analog resiniferatoxin (RTX). Twenty-four hours following RTX injection response latencies to noxious heat were significantly increased for both the ligated and unligated hind paws. In addition, increased responsiveness of the ligated paw to the cold surface was significantly attenuated. The results demonstrate that the enhanced responsiveness to cold and heat following a CCI are mediated in part by RTX-sensitive primary afferents.

A lack of efficacy of some analgesic drugs has been previously described in rats with neuropathic spinal cord injury (SCI) pain. It has been suggested that repeated dosing in these animals over time may eventually lead to efficacy. However, it is also possible that efficacy may diminish over time with repeated dosing. This study evaluated the efficacy of various drugs upon repeated dosing over time in a rat model of SCI pain. Four weeks following an acute spinal cord compression at the mid-thoracic level, rats developed decreased hind paw withdrawal threshold, suggestive of below level neuropathic hypersensitivity. Either cannabinoid (CB) receptor agonist CP 55,940, the anticonvulsant carbamazepine or gabapentin, the antidepressant amitriptyline or vehicle was administered over a period of 7 days. Neither carbamazepine nor amitriptyline demonstrated efficacy either after a single or repeated dosing. Beginning with a 50% efficacious dose of gabapentin, the effect of gabapentin in SCI rats neither increased nor decreased over the treatment period. The antinociceptive effect of CP 55,940 was maintained for the entire treatment period, which was mediated by CB1 but not CB2 receptors. The current data suggest that sustained antinociception can be obtained with some drugs in rats with neuropathic SCI pain. Furthermore, the current data do not substantiate the notion that repeated treatment with initially ineffective drugs will eventually lead to efficacy; treatments that are not acutely effective are unlikely to demonstrate clinical efficacy.

Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

Light-induced degradation and light-induced degradation after current-induced degradation of several types of a-Si solar cells were compared in order to investigate the difference between current-induced degradation and light-induced degradation. Very little difference in the efficiency after long-term light irradiation is observed between samples which were degraded by light- after current-induced degradation and those which were degraded by light only. Little difference in the collection efficiency spectra and the depth profiles of the DICE (dynamic inner collection efficiency) is also observed between the cells degraded by these two processes. The possibility of applying the current-induced degradation method to the stabilization of a-Si solar modules is indicated.

Structural properties for CuInSe2 films formed by two methods, (a) three-source co-evaporation and (b) selenization of Cu/In/Se-stacked layer, were studied using X-ray diffraction, Raman scattering and SEM imaging. It is found that films by co-evaporation show stronger (112) orientation than the selenization films and A1 mode peak in Raman spectra is seen for selenized films even with a ratio of Cu/In < 0.6 in which composition the peak relating to A1 mode disappeas in co-evaporated films. A conversion efficiency of 10.5% was obtained for a CuInSe2 solar cell using the co-evaporated film.

Dark current‐voltage (J‐V) characteristics of p‐i‐n a‐Si solar cells are studied to clarify the effect of the p/i interface layer on the open‐circuit voltage (Voc). It is shown that the recombination current in the p/i interface region is predominant in the a‐Si solar cells with an i‐layer thickness of less than 200 nm and has a great effect on the dark‐current transport in the solar cells. It is also shown that the current transport of the cells with the p/i interface layer of constant band gap of a thickness of more than 14 nm is effectively the same as that of a cell in which the band gap of the whole i layer is equal to that of the interface layer. A model in which the dark current of the cell consists of the recombination current at the p/i interface and the recombination current in the bulk region of the i layer is proposed. Using this model, the Voc degradation for the a‐Si solar cells with the p/i interface layer is shown to be due to the defects generated in the i layer.

Inserting an endoscope into colon requires very technical procedure and it is difficult in some cases even for experienced doctors. Although active colonoscopes have been researched, these instruments are still in the development stage. Mechanisms for this application are required to be soft enough not to injure the colon wall and being deformable enough to adapt to the curves of the colon. In addition, the mechanisms must generate distributed force adequate for traveling. These requirements are difficult to be satisfied using conventional mechanisms and actuators. We have designed and developed two types of new driving mechanism using pneumatic rubber actuators and made their feasibility tests. One mechanism is "thin tube wave generator": introducing pulse pneumatic flows to a thin rubber tube causes traveling deformation waves on the tube surface, which drives an object placed on the tube. The other mechanism is "round bubbler": a rubber tube which has four chambers in it is wound around the colonoscope to cause traveling deformation waves on the scope surface by sending pneumatic pressures to each chamber sequentially. In this paper, first, we discuss the driving mechanisms, pneumatic control systems, and basic characteristics of these two mechanisms. Then, based on the basic experimental discussions, we fabricated special rubber mechanisms to fit around a conventional colonoscope, and conducted insertion experiments using an intestinum model and an existing colonoscope under various conditions. The experimental results are very promising

The reliability of oxide confined 850 nm VCSELs for 10 Gb/s operation was investigated. The median life with criteria of 2 dB decrease of output power at environmental temperature of 25/spl deg/C was over 10 million hours.

1.3 /spl mu/m GaInNAsSb based VCSELs with improved active region structure are reported. By changing the active region, maximum lasing temperature of over 105/spl deg/C and single mode output power at 85/spl deg/C of 0.35 mW were obtained.

P2P content distribution networks are collecting interest to efficiently deliver rich contents such as audio and video. Stream interruption caused by relay peers dropping out of the P2P network is a problem in P2P live streaming systems. In this paper, we propose a P2P live streaming system with low stream interruption. In the proposed system, peers are connected to the peers with low drop-out probability and a wide and short P2P network is constructed. Also, multiple paths to the source is considered. We show the improvement in the interruption time by our algorithm through simulations.

1.3 /spl mu/m-range GaInNAsSb material and its application to VCSELs were investigated. GaInNAsSb active layer that include the small amount of Sb can be easily grown in 2 dimensional manner as compared with GaInNAs due to the suppression of the formation of 3-dimensional growth in MBE growth. We obtained the lowest Jth per well (150A/cm/sup 2//well) as for the edge-emission type lasers due to the high quality of GaInNAsSb-QW. Using this material for the active media, we accomplished the first CW operation of 1.3 /spl mu/m-range GaInNAsSb VCSELs.

1.3 /spl mu/m-range GaInNAsSb quantum well lasers that include small amount of Sb as the composition were confirmed to increase the critical thickness at which the growth mode changes from the 2-dimentional (2-D) growth to the 3-dimentional (3-D) growth. By adopting GaNAs barriers instead of GaAs barriers, we obtained the very low Jth of 160A/cm/sup 2//well up to 5QWs. We applied this material to the VCSELs, and the obtained threshold currents of 10ch-arrays are as uniform as 1.85/spl plusmn/0.15mA at 25/spl deg/C.

Effects of preparation conditions for precursors in selenization with H/sub 2/Se on film properties of CuInSe/sub 2/ and CuIn/sub 1-x/Ga/sub x/Se/sub 2/ were studied. Using a Cu/In stacked layer precursor prepared at temperature of 200 C, grain sizes for selenized CuInSe/sub 2/ films became as large as 2 /spl mu/m. It was found from XRD analysis that MoSe/sub 2/ was formed at the boundary to the Mo back electrode for a selenization process using the stacked layer precursors. Formation of MoSe/sub 2/ was suppressed using a Cu-In-Se mixed compound precursor. Grain sizes for selenized CuInSe/sub 2/ films with Cu-In-Se precursors prepared at 200 C were about 1 /spl mu/m. A glass/Mo/CuIn(Ga)Se/sub 2CdZnS/ZnO cell structure was fabricated to study the effects of the precursor on cell performances. It was found that Voc was improved for Cu-In-Se precursors as substrate temperature increased. A fill factor exceeding 0.7 was obtained using Cu-In-Se precursors prepared at 200 C. A value of Voc was improved with Ga doping near the boundary to the Mo back electrode. Using Se mixed precursors, conversion efficiencies of 12.6% and 11.7% were obtained for CuInSe/sub 2/ solar cells and CuIn/sub 1-x/Ga/sub x/Se/sub 2/ solar cells. >

A study was made of properties of CuInSe/sub 2/, CuInGaSe/sub 2/ and CdZnS films and the performance of solar cells fabricated with these films. An efficiency of 10.5% for the cell with CuInSe/sub 2/ film prepared by coevaporation and Cd/sub 1-x/Zn/sub x/ S (x=0.19) film by EB evaporation was obtained. For the CuInGaSe/sub 2/-based cell, an efficiency of 10.0% was obtained. PL emission spectra obtained on CuInSe/sub 2/ films resulting in high-efficiency devices has two peaks in the range of 0.85-0.93 eV. For the low-efficiency CuInSe/sub 2/ films, a single peak is observed at a higher photon energy. >

Hydrogenated amorphous silicon (a-Si:H)-based solar cells with a double-junction tandem structure have been studied with a view to improving the light-induced degradation in photovoltaic performance. Conversion efficiencies of 11.4% for a 1 cm/sup 2/ tandem cell. 9.7% (in total area efficiency) for a 30 cm*40 cm tandem submodule, and 8.5% (in total area efficiency) for a 40 cm*120 cm tandem submodule were achieved. The stabilized efficiency of the 11.4% cell after a 1000 h light soaking was 10% under open-circuit conditions. >

For the short-distance and high-speed optical interconnection light source, 850 nm vertical cavity surface emitting lasers (VCSELs) are very attractive. VCSELs are expected to be used with a high frequency modulation over 10 Gbps. In this study, we fabricated 850 nm oxide confined VCSELs, and measured 10 Gbps operations for both VCSELs confirmed on carrier and TO-can.

The analgesic effect of intrathecal injection of epibatidine, clonidine and neostigmine, compounds that elevate ACh, was examined in the formalin test, a model of post-injury central sensitization in the rat. The compounds were injected alone and in combination. Intrathecal injection of epibatidine alone did not alter pain behaviors, compared to vehicle-treated rats. Intrathecal injection of clonidine dose-dependently reduced tonic pain behaviors (ED(50)+/-95% confidence limits=6.7+/-4.8 microg). The combination of clonidine and epibatidine (C:E), in the ratio of 26:1, dose-dependently reduced tonic pain behaviors; and the ED(50) of C:E was 1.1+/-0.98 microg a significant 6-fold leftward shift of the dose response curve, compared with clonidine alone. The antinociceptive effect of C:E (26:1) was attenuated by pre-treatment with the nAChR antagonist mecamylamine. Neostigmine dose-dependently reduced tonic pain behaviors (ED(50)=1.5+/-1.3 microg). The combination of neostigmine and epibatidine, in a ratio of 8:1, significantly shifted the dose response curve 4-fold to the left (ED(50)=0.4+/-0.3 microg). The effect is mediated in part by the activation of the nAChR and possibly by the enhanced release of ACh. These data demonstrate significant enhancement of the antinociceptive effects of spinally delivered analgesics by a nAChR agonist, suggesting that this class of compounds may have utility as adjuvants when combined with conventional therapeutics.

Following tissue injury, spinal neurons increase in spontaneous activity and in responsiveness to peripheral stimulation. These changes in spinal neurons may underlie abnormal pain behavior. Nicotinic acetylcholine receptor (nAChR) agonists are analgesic when evaluated in animal models of pain, but it is not known if the nAChRs differentially modulate acute and tonic pain. To test this, mecamylamine, a non-subtype selective nAChR antagonist, was systemically injected into rats prior or after hind paw injection of formalin. Formalin injection results in biphasic pain-related behaviors, characterized by a first phase (i.e. acute pain) immediately following formalin injection, then by a second phase (i.e. tonic pain) 15-60 min after formalin injection. Either pre- or post-formalin treatment with mecamylamine decreased phase 1 behaviors and significantly increased phase 2 pain behaviors in a dose-dependent manner. These results suggest that nAChRs may exert opposing effects on acute versus tonic pain and, as such, may have implications for the potential development of nAChR ligands for the treatment of pain.

Abnormal pain-related behaviour that accompanies peripheral nerve injury may be the result of altered spinal neuronal function. The long-term loss of inhibitory function by GABA neurons in particular may be a mechanism by which abnormal neural hyperactivity occurs, leading to exaggerated sensory processing following nerve injury. In order to assess this, changes in spinal GABA immunoreactivity at several time points following constriction nerve injury were quantified in parallel with behavioural assessments of abnormal sensory responses to noxious and innocuous stimuli. In addition, the effects of spinal adrenal medullary transplants were determined since previous findings have demonstrated alleviation of behavioural pain symptoms by such transplants. In response to unilateral sciatic nerve injury, GABAergic profiles normally found in lumbar dorsal horn laminae I-III significantly decreased. The decrease was apparent three days following ligation, particularly on the side ipsilateral to the nerve injury. By two weeks, no GABAergic profiles could be seen, with the deficit appearing in the spinal dorsal horn both ipsilateral and contralateral to the unilateral peripheral nerve injury. Marked decreases in GABA-immunoreactive profiles persisted for at least up to five weeks post-injury, with partial restoration occurring by seven weeks. However, even at seven weeks, losses in GABA-immunoreactive profiles persisted in the dorsal horn ipsilateral to peripheral nerve injury. These findings were comparable in animals receiving control striated muscle transplants. In contrast, adrenal medullary transplants markedly reduced the loss in GABA-immunoreactive profiles at all time-points examined. In addition, GABA-immunoreactive profile levels were normalized near that of intact animals by five to seven weeks following nerve injury in animals with adrenal medullary transplants. Parallel improvements in sensory responses to innocuous and noxious stimuli were also observed in these animals. The results of this study indicate that peripheral nerve injury can result in severe losses in spinal inhibitory mechanisms, possibly leading to exaggerated sensory processes in persistent pain states. In addition, adrenal medullary transplants may provide a neuroprotective function in promoting recovery and improving long-term survival of GABAergic neurons in the spinal dorsal horn which have been damaged by excitotoxic injury.

Adrenal medullary chromaffin cells implanted into the spinal subarachnoid space can reduce abnormal pain-related responses in chronic pain models. Persistent pain is thought to involve the activation of N-methyl-D-aspartate (NMDA) receptors and subsequent production of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP). Changes in dorsal horn levels of cGMP in the rat were determined in conjunction with alterations in pain behaviors following peripheral nerve injury and adrenal medullary transplantation. Results indicated increased spinal cGMP levels in parallel with thermal and mechanical hyperalgesia and tactile allodynia consequent to chronic constriction injury of the sciatic nerve in rats. Adrenal medullary, but not control transplants, attenuated the hyperalgesia and allodynia and decreased spinal cGMP content. These results suggest that adrenal medullary transplants may reduce abnormal pain by intervention in the spinal NMDA-NO cascade.

Peripheral nerve injury causes abnormal sensory processing, possibly due in part to neuroplastic changes in the CNS. Following chronic constriction injury of the sciatic nerve, transsynaptic degeneration is suggested by the presence of “dark neurons” found in superficial laminae of spinal cord. Previous studies in our laboratory have shown that grafts of adrenal medullary cells into the spinal subarachnoid space can reduce abnormal pain due to peripheral nerve injury. A possible mechanism for these beneficial effects is the reduction or interruption of excitotoxic events that lead to pathological CNS changes. In order to examine this, 2 weeks after unilateral sciatic nerve ligation using a chronic constriction injury model, animals received either adrenal medullary or control striated muscle tissue implanted in the lumbar subarachnoid space. Control striated muscle-transplanted animals with nerve injury displayed thermal hyperalgesia and elevated numbers of dark neurons in the superficial dorsal horn, compared to intact animals. These dark neurons were increased bilaterally, but predominantly ipsilaterally, to nerve injury. In contrast, in animals with adrenal medullary transplants, reduced numbers of dark neurons were found in parallel with reduced hyperalgesia. The low numbers of dark neurons in these animals were similar to age-matched unoperated controls. Two months after nerve ligation, dark neurons were not found in animals with nerve injury, although abnormal ruffled-appearing neurons were still present in untransplanted animals, suggesting partial recovery of damaged spinal neurons. The results of this study suggest that spinal adrenal medullary transplants can attenuate the neuropathological events perpetuating nerve-injury-induced pain by enhancing recovery of spinal neurons from excitotoxic insult.

A new animal model of neuropathic pain utilizing loose ligation of a peripheral nerve has been previously reported. In addition to displaying abnormal pain symptoms such as allodynia and hyperalgesia, physiologic and morphologic changes are seen in spinal cord dorsal horn neurons. Two weeks after ligation of the right common sciatic nerve, rat dorsal horn spinal cord neurons with signs of transsynaptic changes (dark neurons) were found on the side ipsilateral to the nerve injury. A few dark neurons were also found in the contralateral dorsal horn. The distribution of dark neurons in lumbar dorsal horn was limited to the superficial laminae (I-III). The following changes which suggest altered cellular activity were seen under the electron microscope. The nuclear envelope appeared ruffled while the mitochondria appeared normal. In addition, the dense cytoplasm was filled with rosettes of ribosomes as well as extensively developed rough endoplasmic reticulum and distended Golgi apparatus cisternae. While dark neurons had normal appearing somatic synapses, a few appeared atypical. The altered activity of these neurons may lead to abnormal sensory experiences and may be a consequence of central changes in response to persistent peripheral nerve injury. The purpose of the present study was to assess morphologic, hence functional, changes in spinal cord neurons in response to peripheral nerve constriction injury which evokes chronic pain-related behaviour.

Recent data have suggested that adrenal medullary tissue allografts in the spinal cord subarachnoid space, by releasing catecholamines and opioid peptides, attenuate responses to various acute noxious stimuli and chronic pain-related behaviors. However, the application of this approach is limited by the low availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as the bovine adrenal medulla are plentiful and simple to extract. The goal of this study was to evaluate the potential for bovine chromaffin cell xenografts in the rat spinal subarachnoid space to alleviate chronic pain. This was assessed in an animal model of neuropathic pain induced by loose ligation of the sciatic nerve, which resulted in allodynia, hyperalgesia, and skin temperature abnormalities. Two weeks after nerve injury, animals were implanted with either isolated bovine chromaffin cells or control bovine adrenal fibroblasts in the spinal subarachnoid space at the level of lumbar enlargement and immunosuppressed with cyclosporine A. In animals with chromaffin cell implants, but not fibroblast implants, both cold allodynia and thermal hyperalgesia were markedly reduced or eliminated as early as 1 week following implantation and hind paw skin temperature asymmetry was also normalized. These beneficial effects were maintained without decrement or apparent tolerance for the 9 week course of the symptomology. The analgesic effects of chromaffin cell grafts were partially attenuated following i.t. injection of naloxone and phentolamine separately and in combination, suggesting involvement of spinal opioid and alpha-adrenergic receptors. Following termination of behavioral studies, immunocytochemical analysis revealed robust survival of chromaffin cells in the implants. These results demonstrate that chromaffin cell xenografts may be effective in alleviating pain of neurogenic origin.

Persistent sensory abnormalities consequent to injury may involve prolonged neuroplastic changes in the spinal cord similar to those in long-term potentiation. Molecular markers, like the putative nitric oxide synthase, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), can be useful indicators of increased neuronal activity. Peripheral nerve injury markedly increased NADPH-d-labeling in sensory regions of the spinal cord, paralleling induction of abnormal pain (hyperalgesia). Both NADPH-d activation and hyperalgesia were reversed by transplantation of opioid/catecholamine-producing adrenal medullary tissue into the spinal subarachnoid space. These results suggest that adrenal medullary transplants can attenuate abnormal neuronal activity consequent to injury.

Adrenal medullary transplants in the spinal subarachnoid space, by providing a continual source of opioid peptides and catecholamines, offer a potentially important adjunct in the management of chronic pain. While previous studies have shown that this approach is effective against high-intensity phasic stimuli, adrenal medullary implants need to be evaluated against long-term and abnormal pain syndromes before transplantation can be used for human chronic pain. Using a recently developed model of painful peripheral neuropathy, the effects of adrenal medullary chromaffin cells transplanted into the subarachnoid space was evaluated. Peripheral mononeuropathy was induced by loosely tying 4 ligatures (4-0 chromic gut) around the right sciatic nerve. This procedure produces various pain symptoms including allodynia, hyperalgesia and dysesthesia. Rats were given either adrenal medullary tissue or control striated muscle transplants. Animals with adrenal medullary tissue transplants showed markedly decreased allodynia to innocuous cold as early as 1 week post-transplantation. In addition, hyperalgesia to a noxious thermal stimulus was eliminated by adrenal medullary, but not control, transplants. Touch-evoked allodynia was only slightly reduced by adrenal medullary transplants. In addition, indicators of spontaneous pain appeared reduced in animals with adrenal medullary transplants. These findings indicate that adrenal medullary transplants may be effective in reducing neuropathic pain.

Si ion implantation was widely used to synthesize specimens of SiO2 containing supersaturated Si and subsequent high temperature annealing induces the formation of embedded luminescent Si nanocrystals. In this work, the potentialities of excimer UV-light (172 nm, 7.2 eV) irradiation and rapid thermal annealing (RTA) to enhance the photoluminescence and to achieve low temperature formation of Si nanocrystals have been investigated. The Si ions were introduced at acceleration energy of 180 keV to fluence of 7.5 x 1016 ions/cm2. The implanted samples were subsequently irradiated with an excimer-UV lamp. After the process, the samples were rapidly thermal annealed before furnace annealing (FA). Photoluminescence spectra were measured at various stages at the process. We found that the luminescence intensity is strongly enhanced with excimer-UV irradiation and RTA. Moreover, effective visible photoluminescence is found to be observed even after FA at 900 oC, only for specimens treated with excimer-UV lamp and RTA. Based on our experimental results, we discuss the effects of excimer-UV lamp irradiation and RTA process on Si nanocrystals related photoluminescence.

The good-quality a-SiGe:H is produced in a triode rf glow discharge system from SiH 4 +GeH 4 mixture. This a-SiGe:H possesses very sharp Urbach tail (Urbach energy E 0 =50meV) and better photoelectrical properties as compared with films produced in a conventional diode system. It is also shown that an inhomogeneous microstructure is observed in a-SiGe:H films with poor photoelectrical properties.