Search Results (13)

Myricetin (MYR), a naturally occurring flavonoid widely distributed in fruits and vegetables, was investigated for its potential to reduce inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc), which is associated with hyperalgesia. The study also compared MYR’s impact with that of celecoxib (CEL), a non-steroidal anti-inflammatory drug (NSAID). To induce inflammation, Complete Freund’s adjuvant was injected into the whisker pads of rats. Subsequently, we measured the mechanical escape threshold by applying mechanical stimuli to the orofacial region. We found that inflamed rats exhibited a significantly lower threshold compared to naive rats (each group, n = 4). This reduced threshold returned to the naive level two days after the administration of MYR (16 mg/kg, i.p.), CEL (10 mg/kg, i.p.), and a combination of MYR (8 mg/kg, i.p.) + CEL (5 mg/kg, i.p.). To investigate the nociceptive neural response to orofacial mechanical stimulation, we performed extracellular single-unit recordings to measure the activity of SpVc wide-dynamic range (WDR) neurons in anesthetized subjects. In inflamed rats, administration of MYR, CEL, or 1/2MYR + 1/2CEL (each group, n = 4) significantly reduced both the average spontaneous activity and the evoked firing rate of SpVc neurons in response to non-painful and painful mechanical stimuli. The increased average receptive field size in inflamed rats was normalized to the naive level following treatment with MYR, CEL, or 1/2MYR + 1/2CEL. These findings suggest that MYR administration can mitigate inflammatory hyperalgesia by reducing the heightened excitability of SpVc WDR neurons. This supports the notion that MYR could be a viable therapeutic option in complementary and alternative medicine for preventing trigeminal inflammatory mechanical hyperalgesia, potentially serving as an alternative to selective cyclooxygenase-2 blockers. Full article

This study investigated the potential of astaxanthin (AST), a natural carotenoid, to mitigate inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc) and the associated hyperalgesia. The efficacy of systemic AST application was compared to that of celecoxib (CEL). Inflammation was induced by injecting Complete Freund’s adjuvant into the whisker pads of rats. The mechanical escape threshold was then assessed by delivering mechanical stimuli to the orofacial region. Although inflamed rats exhibited a significantly lower mechanical threshold compared to naïve rats, this threshold was restored to normal levels two days after treatment with AST, CEL, and the 1/2 CEL + 1/2 AST combination. The activity of SpVc wide-dynamic range (WDR) neurons was measured using extracellular single-unit recordings in response to mechanical stimulation of the orofacial area under anesthesia. In inflamed rats, AST, CEL, and 1/2 CEL + 1/2 AST administration significantly reduced the average firing rate of these neurons elicited by both non-noxious and noxious mechanical stimuli. In addition, all three treatments significantly decreased the heightened average spontaneous activity of SpVc neurons and normalized the increased average receptive field size in inflamed rats. This study provides evidence that systemic AST administration attenuates inflammatory mechanical hyperalgesia. This action is associated with the suppression of hyperexcitability in nociceptive SpVc WDR neurons, likely through the inhibition of the cyclooxygenase-2 signaling pathway. These findings support the potential of AST as a therapeutic agent for complementary and alternative medicine. It may provide a valuable alternative to non-steroidal anti-inflammatory drugs for the prevention of trigeminal inflammatory mechanical hyperalgesia. Full article

While the modulation of the excitatory and inhibitory neuronal transmission by the phytochemical flavonoid, myricetin (MYR), has been noted in the nervous system, the way in which MYR affects the excitability of nociceptive sensory neurons in vivo remains to be established. This study aimed to explore whether administering MYR intravenously, in acute doses, to rats, diminishes the excitability of SpVc wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Recordings of extracellular single units were obtained from SpVc neurons when orofacial mechanical stimulation was applied to anesthetized rats. The average firing rate of SpVc WDR neurons, to both non-noxious and noxious mechanical stimuli, was significantly and dose-dependently inhibited by MYR (1–5 mM, intravenously), and the maximum reversible inhibition of the discharge frequency, for both non-noxious and noxious mechanical stimuli, occurred within 5–10 min. The suppressive effects of MYR continued for about 20 min. These findings indicate that an acute, intravenous administration of MYR reduces the SpVc nociceptive transmission, likely through the inhibition of the CaV channels and by activating the Kv channels. Therefore, MYR might be utilized as a treatment for trigeminal nociceptive pain, without causing side effects. Full article

Although astaxanthin (AST) has demonstrated a modulatory effect on voltage-gated Ca²⁺ (Cav) channels and excitatory glutamate neuronal transmission in vitro, particularly on the excitability of nociceptive sensory neurons, its action in vivo remains to be determined. This research sought to determine if an acute intravenous administration of AST in rats reduces the excitability of wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. In anesthetized rats, extracellular single-unit recordings were carried out on SpVc neurons following mechanical stimulation of the orofacial area. The average firing rate of SpVc WDR neurons in response to both gentle and painful mechanical stimuli significantly and dose-dependently decreased after the application of AST (1–5 mM, i.v.), and maximum suppression of discharge frequency for both non-noxious and nociceptive mechanical stimuli occurred within 10 min. These suppressive effects persisted for about 20 min. These results suggest that acute intravenous AST administration suppresses the SpVc nociceptive transmission, possibly by inhibiting Cav channels and excitatory glutamate neuronal transmission, implicating AST as a potential therapeutic agent for the treatment of trigeminal nociceptive pain without side effects. Full article

Since the inception of spinal cord stimulation (SCS) in 1967, the technology has evolved dramatically with important advancements in waveforms and frequencies. One such advancement is Nevro’s Senza^® SCS System for HF10, which received Food and Drug and Administration (FDA) approval in 2015. Low-frequency SCS works by activating large-diameter Aβ fibers in the lateral discriminatory pathway (pain location, intensity, quality) at the dorsal column (DC), creating paresthesia-based stimulation at lower-frequencies (30–120 Hz), high-amplitude (3.5–8.5 mA), and longer-duration/pulse-width (100–500 μs). In contrast, high-frequency 10 kHz SCS works with a proposed different mechanism of action that is paresthesia-free with programming at a frequency of 10,000 Hz, low amplitude (1–5 mA), and short-duration/pulse-width (30 μS). This stimulation pattern selectively activates inhibitory interneurons in the dorsal horn (DH) at low stimulation intensities, which do not activate the dorsal column fibers. This ostensibly leads to suppression of hyperexcitable wide dynamic range neurons (WDR), which are sensitized and hyperactive in chronic pain states. It has also been reported to act on the medial pathway (drives attention and pain perception), in addition to the lateral pathways. Other theories include a reversible depolarization blockade, desynchronization of neural signals, membrane integration, glial–neuronal interaction, and induced temporal summation. The body of clinical evidence regarding 10 kHz SCS treatment for chronic back pain and neuropathic pain continues to grow. There is high-quality evidence supporting its use in patients with persistent back and radicular pain, particularly after spinal surgery. High-frequency 10 kHz SCS studies have demonstrated robust statistically and clinically significant superiority in pain control, compared to paresthesia-based SCS, supported by level I clinical evidence. Yet, as the field continues to grow with the technological advancements of multiple waveforms and programming stimulation algorithms, we encourage further research to focus on the ability to modulate pain with precision and efficacy, as the field of neuromodulation continues to adapt to the modern healthcare era. Full article

Vincristine is a vinca alkaloid anti-mitotic drug with a broad spectrum of effects on solid and hematologic cancers. The major dose-limiting factor of this anti-cancer regimen is painful peripheral neuropathy. However, no gold-standard analgesic option has been used clinically. In this study, we investigated the effects and mechanism of bee venom acupuncture (BVA) to alleviate peripheral neuropathic pain induced by repeated intraperitoneal infusions of vincristine (1 mg/kg/day, days 1–5 and 8–12) in rats. Subcutaneous injection with bee venom (BV, 1.0 mg/kg) at the ST36 acupoint ameliorated cold and mechanical hypersensitivity (i.e., aberrant withdrawal responses in acetone drop and von Frey hair tests, respectively). In vivo extracellular recording demonstrated that BVA inhibited cutaneous cold (acetone) and mechanical (brush, press, and pinch) stimuli-elicited abnormal hyperexcitation of the spinal wide dynamic range (WDR) neurons in vincristine-treated rats. In addition, the microinjection of lidocaine into the ipsilateral locus coeruleus or the antagonism of the spinal α₂-adrenergic receptors clearly reversed the effects of BVA on cold and mechanical hypersensitivity, indicating a vital role of the descending noradrenergic modulation in analgesia. These findings suggest that BVA could be a potential therapeutic option for vincristine-induced peripheral neuropathy. Full article

The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation. Full article

Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain. Full article

In this paper, a wide dynamic range (WDR) CMOS image sensor (CIS) with a charge splitting gate (SG) and two storage diodes (SDs) is presented. By using single-gate on/off control with the SG, photocurrent path to the first (SD1) or second storage diodes (SD2) is switched alternatively and periodically during exposure and signal electrons generated in a photodiode (PD) are transferred to and accumulated in the SD1 or SD2. By setting a large ratio of the off-time to on-time of the SG, two different sensitivity signals, which are originated by the same photodiode, are generated and a WDR image signal is obtained. This technique has a distinct advantage on mitigating the problem of motion artifact in WDR imaging with high and low sensitivity signals and flexible dynamic control of the dynamic range. An experimental WDR CMOS image sensor with 280 (H) × 406 (V)-pixel array consisting of 14 sub-arrays, each of which have 20 (H) × 406 (V) pixels, was implemented and tested. For the SG on/off-time ratio of 30 and 279, the DR of 93 dB and 104 dB, respectively, was demonstrated. The effect of the proposed WDR imaging operation on the reduced motion artifact was experimentally confirmed. Full article

Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α₁-adrenergic receptor antagonists, 10 μg); however, idazoxan (α₂-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α₁-adrenergic receptors. Full article

Tone mapping algorithms are used to adapt captured wide dynamic range (WDR) scenes to the limited dynamic range of available display devices. Although there are several tone mapping algorithms available, most of them require manual tuning of their rendering parameters. In addition, the high complexities of some of these algorithms make it difficult to implement efficient real-time hardware systems. In this work, a real-time hardware implementation of an exponent-based tone mapping algorithm is presented. The algorithm performs a mixture of both global and local compression on colored WDR images. An automatic parameter selector has been proposed for the tone mapping algorithm in order to achieve good tone-mapped images without manual reconfiguration of the algorithm for each WDR image. Both algorithms are described in Verilog and synthesized for a field programmable gate array (FPGA). The hardware architecture employs a combination of parallelism and system pipelining, so as to achieve a high performance in power consumption, hardware resources usage and processing speed. Results show that the hardware architecture produces images of good visual quality that can be compared to software-based tone mapping algorithms. High peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) scores were obtained when the results were compared with output images obtained from software simulations using MATLAB. Full article

Usually Wide Dynamic Range (WDR) sensors that autonomously adjust their integration time to fit intra-scene illumination levels use a separate digital memory unit. This memory contains the data needed for the dynamic range. Motivated by the demands for low power and chip area reduction, we propose a different implementation of the aforementioned WDR algorithm by replacing the external digital memory with an analog in-pixel memory. This memory holds the effective integration time represented by analog encoding voltage (AEV). In addition, we present a “ranging” scheme of configuring the pixel integration time in which the effective integration time is configured at the first half of the frame. This enables a substantial simplification of the pixel control during the rest of the frame and thus allows for a significantly more remarkable DR extension. Furthermore, we present the implementation of “ranging” and AEV concepts on two different designs, which are targeted to reach five and eight decades of DR, respectively. We describe in detail the operation of both systems and provide the post-layout simulation results for the second solution. The simulations show that the second design reaches DR up to 170 dBs. We also provide a comparative analysis in terms of the number of operations per pixel required by our solution and by other widespread WDR algorithms. Based on the calculated results, we conclude that the proposed two designs, using “ranging” and AEV concepts, are attractive, since they obtain a wide dynamic range at high operation speed and low power consumption. Full article

Modern “smart” CMOS sensors have penetrated into various applications, such as surveillance systems, bio-medical applications, digital cameras, cellular phones and many others. Reducing the power of these sensors continuously challenges designers. In this paper, a low power global shutter CMOS image sensor with Wide Dynamic Range (WDR) ability is presented. This sensor features several power reduction techniques, including a dual voltage supply, a selective power down, transistors with different threshold voltages, a non-rationed logic, and a low voltage static memory. A combination of all these approaches has enabled the design of the low voltage “smart” image sensor, which is capable of reaching a remarkable dynamic range, while consuming very low power. The proposed power-saving solutions have allowed the maintenance of the standard architecture of the sensor, reducing both the time and the cost of the design. In order to maintain the image quality, a relation between the sensor performance and power has been analyzed and a mathematical model, describing the sensor Signal to Noise Ratio (SNR) and Dynamic Range (DR) as a function of the power supplies, is proposed. The described sensor was implemented in a 0.18 um CMOS process and successfully tested in the laboratory. An SNR of 48 dB and DR of 96 dB were achieved with a power dissipation of 4.5 nW per pixel. Full article