The effect of oral massage intervention on oral hygiene at home care.

INTRODUCTION: Oral hygiene for individuals with disabilities living at home heavily relies on caregiver assistance. This study investigates differences in mouth opening, dental plaque index and halitosis grade among home-dwelling individuals with and without oral massage intervention. It is important to consider that extended bedridden periods, the presence of nasogastric tubes and difficulties in mouth opening can affect caregivers' oral cleaning effectiveness. METHOD: This single-blind controlled experiment spanned 12 weeks. Primary caregivers underwent a 15- to 20-min demonstration. The experimental group received guidance on the Bass brushing method, instructions for using oral cleaning tools and training in oral massage. The control group received guidance on the Bass brushing method and instructions for oral cleaning tools. Measurement tools included basic participant information, oral examination records, mouth opening assessments, dental plaque index evaluations and halitosis ratings. RESULTS: The study included 38 subjects, all over 80 years old with disabilities. Dental plaque index significantly improved after massage (p = 0.001). Compared to their pre-massage conditions, the experimental group showed significant improvements in maximum mouth opening (11.65-20.71 mm, p = 0.001), dental plaque index (98.04%-59.74%, p < 0.0001) and halitosis rating (4.12-3.76, p = 0.034). CONCLUSIONS: Oral massage effectively improved mouth opening, reduced the dental plaque index and lowered halitosis ratings in the experimental group, underscoring its positive impact on oral hygiene. The study's insights can significantly benefit oral care for individuals with disabilities living at home.

Star-ECG: Visualization of Electrocardiograms for Arrhythmia and Heart Rate Variability.

Conventional electrocardiograms (ECG) are displayed in one dimension. Reading one-dimensional ECG waveform becomes challenging when one wants to visualize the heart rate variability with naked eye. Some ECG visualization techniques have been proposed. However, they rely on domain knowledge to comprehend the heart rate variability. To improve the readability for patients and non-experts, we introduce Star-ECG, a novel ECG visualization approach. Such approach projects ECG waveforms onto a two-dimensional plane in a circular form. We demonstrate that Star-ECG offers not only easily deciphered visualization of cardiac abnormalities and heart rate variability, but also the application of state-of-the-art arrhythmia classification with integrated deep neural networks. We also report positive user feedback from both experts and non-experts that Star-ECG can provide readable and helpful information to monitor cardiac activities.

Effect of tongue-to-palate resistance training on tongue strength in healthy adults.

OBJECTIVE: Tongue strength is crucial for safe and efficient oropharyngeal swallowing. This study examined the effect of tongue-to-palate resistance training (TPRT) on anterior and posterior tongue strength by conducting a prospective, randomized, parallel allocation trial. METHODS: Ninety-one healthy adults were recruited in this study and were randomly assigned to an experimental group (n = 44) or a control group (n = 47). The experimental group performed TPRT for 8 weeks (5 days per week), whereas the control group performed the usual daily activities. Tongue strength was measured using the Iowa Oral Performance Instrument (IOPI) before and after the practice program was conducted at weeks 2, 4, 6, and 8, to evaluate the feasibility of the developed training protocol. RESULTS: This experimental group demonstrated more improvements in both anterior tongue strength (p < .05) and posterior tongue strength (p < .05). The positive effects of the intervention on tongue strength appeared at 8 weeks for the anterior region and 2 weeks for the posterior region. CONCLUSIONS: These findings illustrate that TPRT can improve tongue strength. It is suggested that people integrate this exercise protocol into their daily life, positive change in tongue strength may prevent or halt presbyphagia.

Neuroprotection in the Acute Stage Enables Functional Recovery Following Repair of Chronic Cervical Root Transection After a 3-Week Delay.

BACKGROUND: Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery. OBJECTIVE: To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair. METHODS: First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury. RESULTS: Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance. CONCLUSION: Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.

Elevated galanin receptor type 2 primarily contributes to mechanical hypersensitivity after median nerve injury.

In this study, we investigated temporal changes in galanin receptor type 2 (GalR2) expression in NF200-, galanin-, neuropeptide Y (NPY)-, and neuronal nitric oxide synthase (nNOS)-like immunoreactive (LI) dorsal root ganglion (DRG) neurons after median nerve chronic constriction injury (CCI), and the effects of GalR2 on c-Fos expression in the cuneate nucleus (CN). Double immunofluorescence labeling methods were used to appraise changes in GalR2 expression in NF200-LI, galanin-LI, NPY-LI, and nNOS-LI DRG neurons after CCI. The von Frey assay was used to assess the efficiency of intraplantar administration of saline, M871 (a GalR2 antagonist), or AR-M1896 (a GalR2 agonist) on neuropathic signs of rats with CCI. The effects of alterations in c-Fos expression were assessed in all treatments. The percentage of GalR2-LI neurons in lesioned DRGs increased and peaked at 1 week after CCI. We further detected that percentages of GalR2-LI neurons labeled for NF200, galanin, NPY, and nNOS significantly increased following CCI. Furthermore, M871 remarkably attenuated tactile allodynia, but the sensation was slightly aggravated by AR-M1896 after CCI. Consequentially, after electrical stimulation of the CCI-treated median nerve, the number of c-Fos-LI neurons in the cuneate nucleus (CN) was significantly reduced in the M871 group, whereas it increased in the AR-M1896 group. These results suggest that activation of GalR2, probably through NPY or nitric oxide, induces c-Fos expression in the CN and transmits mechanical allodynia sensations to the thalamus.

Data on the expression of leptin and leptin receptor in the dorsal root ganglion and spinal cord after preganglionic cervical root avulsion.

Leptin (Lep) is mainly, although not exclusively, secreted by adipocytes. In addition to regulating lipid metabolism, it is also a proinflammatory factor and involved in the development of neuropathic pain after peripheral nerve injuries (PNI) (Lim et al., 2009; Maeda et al., 2009) [1,2]. Leptin or its messenger ribonucleic acid expression has been found in various brain regions normally and in the dorsal horn after PNI (Lim et al., 2009; Ur et al., 2002; La Cava et al., 2004; White et al., 2004) [1,[3], [4], [5]]. However, the expression pattern of Lep and Leptin receptor (LepR) after preganglionic cervical root avulsion (PCRA) is still unknown. We provide data in this article related to Chang et al. (2017) [6]. Here, our data showed a profound Lep and LepR expression in the neurons of dorsal root ganglion (DRG) after PCRA. Moreover, the expression of Lep and LepR were also identified in significant portions of the neurons and microglia located in the dorsal horn. The roles of these increased expressions in the development of neuropathic pain after PCRA deserve further study.

Leptin is essential for microglial activation and neuropathic pain after preganglionic cervical root avulsion.

AIMS: Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown. MAIN METHODS: Preganglionic avulsion of the left 6th-8th cervical roots was performed in C57B/6J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal and supraspinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity. KEY FINDINGS: Leptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis in the dorsal horn and brainstem. Furthermore, increase in the expression of CD86 and iNOS, and Wallerian degeneration were noted in the spinal cord. The administration of exogenous leptin to leptin-deficient mice reversed these effects. SIGNIFICANCE: We concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.

Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection.

Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in the treatment of spinal cord injury.

Repairing the ventral root is sufficient for simultaneous motor and sensory recovery in multiple complete cervical root transection injuries.

AIM: In multiple cervical root transection injuries, motor and sensory recovery has been demonstrated after repairing both dorsal and ventral roots with autologous grafts applied to the dorsal and ventral aspects, respectively. However, in clinical situations, autologous grafts may not be sufficient to repair both roots in this situation. In this study, the authors evaluated whether repairing ventral root alone is sufficient for simultaneous sensory and motor function recovery. MAIN METHODS: In the transected group, the left 6th-8th cervical roots were pulled and transected at the spinal cord junction. In the repair group, the transected root was anastomosed to a single autologous nerve graft, which was inserted into the ventral horn through a pial incision. Acidic fibroblast growth factor mixed with fibrin glue was applied to the surgical area. Motor function, sensory function, cortical somatosensory evoked potentials (SSEPs), axon tracing, and CGRP(+) fibers were evaluated. KEY FINDINGS: The repaired rats exhibited simultaneous sensory and motor function recovery. At the 16th weeks, SSEPs reappeared in all animals of the repair group, but not in the transected group. Retrograde axon tracing demonstrated an increased number of sensory neurons in the dorsal root ganglia and regenerating nerve fibers in the dorsal horn. CGRP(+) fibers were significantly increased in the repair group and restricted to laminae I and II. SIGNIFICANCE: This is the first report that in multiple root avulsions with insufficient grafts, repairing ventral roots alone leads to both sensory recovery and motor recovery. This finding may help patients with multiple cervical root avulsions.

Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus.

In this study, we investigated the role of nitric oxide (NO) in lysophosphatidylcholine (LPC) induced peripheral neuropathy by the use of nitric oxide synthase (NOS) inhibitors and NO donor. We found that LPC treatment of the median nerve induced neuropathic pain behaviors (allodynia and hyperalgesia) and nerve demyelination. Immunohistochemistry revealed that the amounts of neuronal NOS-like immunoreative (nNOS-LI) neurons in both the dorsal root ganglion (DRG) and cuneate nucleus (CN) increased and peaked at 1 week after LPC treatment. Following electrical stimulation of the LPC-treated nerve, the number of c-Fos-LI neurons in the ipsilateral CN also increased in a dose-dependent manner following LPC injection and peaked at 1 week. Administration of L-NAME (Nω-Nitro-L-arginine methyl ester) or 7-NI (7-nitroindazole) 1 week after 4% LPC injection attenuated tactile allodynia and thermal hyperalgesia. However, the application of the NO donor S-Nitroso-N-acetylpenicillamine (SNAP) only exacerbated thermal hyperalgesia. After electrical stimulation of the LPC-treated median nerve, the number of c-Fos-LI neurons in the CN diminished in the L-NAME and 7-NI groups, but increased in the SNAP group. Taken together, our findings suggest that advanced NO made by the dramatically increased number of nNOS in the DRG and CN might be involved in the neuropathic sensation and boosted neuronal activity in the CN after LPC treatment.

Changes in GABA and GABA(B) receptor expressions are involved in neuropathy in the rat cuneate nucleus following median nerve transection.

This study examined the relationship between changes in GABA transmission and behavioral abnormalities after median nerve transection. Following unilateral median nerve transection, the percentage of GABA-like immunoreactive neurons in the cuneate nucleus and that of GABA(B) receptor-like immunoreactive neurons in the dorsal root ganglion in the injured side decreased and reached a nadir at 4 weeks after median nerve transection. Four weeks after bilateral median nerve transection and intraperitoneal application with saline, baclofen (2 mg kg⁻¹), or phaclofen (2 mg kg⁻¹) before unilateral electrical stimulation of the injured median nerve, we investigated the level of neuropeptide Y release and c-Fos expression in the stimulated side of the cuneate nucleus. The neuropeptide Y release level and the number of c-Fos-like immunoreactive neurons in the baclofen group were significantly attenuated, whereas those in the phaclofen group had increased compared to the saline group. These findings indicate that median nerve transection reduces GABA transmission, promoting injury-induced neuropeptide Y release and consequently evoking c-Fos expression in cuneate nucleus neurons. Furthermore, this study used the CatWalk method to assess behavioral abnormalities in rats following median nerve transection. These abnormalities were reversed by baclofen treatment. Overall, the results suggest that baclofen treatment block neuropeptide Y release, subsequently lessening c-Fos expression in cuneate neurons and consequently attenuating neuropathic signal transmission to the thalamus.

Decreases of glycine receptor expression induced by median nerve injury in the rat cuneate nucleus contribute to NPY release and c-Fos expression.

AIMS: This study aimed to investigate temporal changes in glycine and its receptor expressions in cuneate neurons after median nerve transection (MNT), and the effects of glycine on neuropeptide Y (NPY) release and c-Fos expression in the cuneate nucleus (CN). MAIN METHODS: Immunohistochemistry methods were used to appraise changes of glycine- and GlyR-like immunoreactive (LI) neurons in the CN after MNT. The alterations in NPY and c-Fos expressions were used to assess the effects of saline, glycine or strychnine treatment. The CatWalk method was used to assess the efficiency of glycine treatment on the neuropathic signs of rats with MNT. KEY FINDINGS: Approximately half of GlyR-LI neurons were fluorogold-labeled cuneothalamic projection neurons in the CN. Following MNT, the number of GlyR-LI neurons significantly decreased in the injured side of CN at 2 and 4 weeks, but the number of glycine-LI neurons remained unchanged. Four weeks after MNT given with electrical stimulation, strychnine significantly decreased the NPY reduction level in the stimulated side CN compared to that of the saline group. However, numbers of c-Fos-LI neurons in the glycine and strychnine groups were both significantly less than that in the saline group. But the paw print width and area in CatWalk analysis showed only a moderate recovery. SIGNIFICANCE: We conjecture that glycine increases glycine-mediated postsynaptic inhibition of cuneate neurons, and also blocks GABAergic neurons containing GlyRs which mediate presynaptic inhibition causing temperate NPY release. Consequently, the compromise results showed a weak reduction in c-Fos expression and a slight amelioration of neuropathic behaviors.

Nitric oxide implicates c-Fos expression in the cuneate nucleus following electrical stimulation of the transected median nerve.

In this study, we investigated whether nitric oxide (NO) modulated injury-induced neuropeptide Y (NPY) releasing and c-Fos expression in the cuneate nucleus (CN) after median nerve transection (MNT). We first examined the temporal changes of neuronal nitric oxide synthase (nNOS) expression in the dorsal root ganglion (DRG) and CN after MNT. Following MNT, the amounts of nNOS-like immunoreactive (nNOS-LI) neurons in the DRG and CN significantly increased as compared with those of the sham-operated rats. Furthermore, 4 weeks after MNT, the increases of nNOS-LI neurons in the DRG and CN were attenuated by pre-emptive lidocaine treatment in a dose-dependent manner. Finally, 4 weeks after MNT, pre-stimulation administration of L-NAME (N (ω)-Nitro-L: -arginine methyl ester) or 7-NI (7-nitroindazole) suppressed the amount of NPY release from the stimulated terminals and thus attenuated c-Fos expression in the CN. Our data implied that NO would modulate neuronal activity in the DRG and CN both after MNT.

Pre-emptive treatment of lidocaine attenuates neuropathic pain and reduces pain-related biochemical markers in the rat cuneate nucleus in median nerve chronic constriction injury model.

This study investigates the effects of lidocaine pre-emptive treatment on neuropathic pain behavior, injury discharges of nerves, neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve chronic constriction injury (CCI). Behavior tests demonstrated that the pre-emptive lidocaine treatment dose dependently delayed and attenuated the development of mechanical allodynia within a 28-day period. Electrophysiological recording was used to examine the changes in injury discharges of the nerves. An increase in frequency of injury discharges was observed and peaked at postelectrical stimulation stage in the presaline group, which was suppressed by lidocaine pre-emptive treatment in a dose-dependent manner. Lidocaine pretreatment also reduced the number of injury-induced NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, the mean number of c-Fos-LI neurons in the CN was significantly correlated to the NPY reduction level and the sign of mechanical allodynia following CCI.

Effects of gentamicin on guinea pig vestibular ganglion function and on substance P and neuropeptide Y.

Previous studies have demonstrated that following intratympanic gentamicin application in the guinea pigs, vestibular evoked myogenic potentials (VEMPs) were absent regardless of stimulation mode using either air-conducted sound (ACS) stimuli or galvanic vestibular stimulation (GVS). Ultrastructurally, both type I hair cells and their calyx terminals were distorted in the saccular macula. However, little is known about the toxic effects of gentamicin on the vestibular ganglion (VG). In this study, absent ACS- and GVS-VEMPs were noted in all the gentamicin-treated ears (100%), which were confirmed by the substantial loss of sensory hair cells in the saccular macula. Moreover, dramatic up-regulation of growth associated protein-43 (GAP-43) expression was detected in the ipsilateral VG neurons. The mean percentage of substance P-like immunoreactive (SP-LI) neurons in the treated VG (81.8±1.9%) was significantly higher than that in the control VG (68.6±3.3%). Conversely, the mean percentage of neuropeptide Y-like immunoreactive (NPY-LI) neurons in the treated VG (13.7±3.8%) was dramatically lower than that in the control VG (49.0±3.8%). Double labeling results shown 82% of SP-LI and 16% of NPY-LI neurons coexpressed with GAP-43, suggested that SP accumulating coincided with NPY decreasing in regenerating VG neurons after gentamicin treatment. Overall, the changes in SP and NPY expression in VG neurons after gentamicin treatment were like to those in the superior cervical ganglion following sympathectomy.

Early expression of injury-induced neuropeptide Y in primary sensory neurons and the cuneate nucleus in diabetic rats with median nerve transection.

In this study we examined the temporal changes in neuropeptide Y (NPY) expression in dorsal root ganglion (DRG) neurons and cuneate nucleus (CN) in streptozotocin (STZ)-induced diabetic rats with or without median nerve transection (MNT). Numerous NPY-like immunoreactive (NPY-LI) neurons and fibers were detected in the DRG and CN of the diabetic MNT (DMNT) rats respectively, but not in those with diabetes-alone. Following MNT, the time-course of NPY expression pattern in the diabetic DRG and CN was similar and both peaked at 2 weeks, which was earlier than those in the non-diabetic MNT rats. Consequently, the expression of neurotrophin-3 (NT-3) immunoreactivity in DRG neurons was coincidentally decreased and reached the nadir at 2 weeks in the diabetic MNT rats, which was also earlier than that in the non-diabetic MNT rats. Following electrical stimulation of the injured nerves, the number of NPY-LI fibers became attenuated and the induced c-Fos-LI cells concurrently appeared in the ipsilateral CN. In the diabetic CN, the number of c-Fos-LI cells also peaked at 2 weeks after MNT, which was consistent with the temporal pattern of changes in NPY expression. The results suggest that in diabetes, MNT induced NPY expression via the reduction of NT-3, and electrical stimulation of the injured median nerve evoked the release of NPY and accordingly more c-Fos-LI cells were identified in the CN. Furthermore, this study demonstrated early NPY and c-Fos expression in the diabetic rats after MNT, suggesting that the development of neuropathic signs may be advanced in hyperglycemic rats.

Assessment of gentamicin-induced vestibulotoxicity by click and galvanic vestibular-evoked myogenic potentials: a guinea pig investigation.

OBJECTIVE: The aim of this investigation carried out with guinea pigs was to study the possible effects of a gentamicin treatment on the saccular macula and on its afferent vestibular ganglion neurons. METHODS: The gentamicin-induced impairment was analyzed using vestibular-evoked myogenic potentials (VEMPs) elicited by both click and galvanic vestibular stimulations (GVS). Fifty microl of saline or gentamicin solution (40 mg/ml) was dropped over the round window membrane of the right (control) and left (lesion) cochleae, respectively. Four weeks after surgery, the VEMPs elicited with clicks and GVS were evaluated for each animal. Then, the animals were sacrificed in order to perform morphological and anti-Nav1.8 immunocytochemical analyses. RESULTS: Click- and GVS-VEMPs were obtained in all of the controls, whereas no potentials were obtained from gentamicin-treated animals. Lesions of sensory cells were observed in the saccular macula. In the injured vestibular ganglion, the percentage of voltage-gated sodium channel Nav1.8-like immunoreactive (Nav1.8-LI) neurons was significantly lower (38.9+/-0.7) than that (53.6+/-3.2) calculated in controls. CONCLUSIONS: Gentamicin-induced impairments of the saccular macula and afferents of guinea pigs can be evaluated by recording both click- and GVS-VEMPs. Both tests provide information on the sacculo-collic reflex pathway and could help a clinical diagnosis of gentamicin intoxication by conventional eardrops in the patient with a perforated eardrum.

Pre-treatment with lidocaine suppresses ectopic discharges and attenuates neuropeptide Y and c-Fos expressions in the rat cuneate nucleus following median nerve transection.

Following peripheral nerve injury, lidocaine application has been demonstrated to suppress injury discharges. However, there is very little information about the effects of lidocaine pre-treatment. The aim of the present study was to examine the effects of pre-treatment with lidocaine on injury discharges of the nerve, and neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve transection (MNT). Rats received either saline or 1%, 5%, or 10% lidocaine applied topically to the median nerve before nerve transection. Electrophysiological recording was used to examine the changes in injury discharges of the nerve at post-injection, transection, pre- and post-electrical stimulation stages in the different groups. Sequential immunohistochemistry was also used to identify the number of NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI cells in the corresponding CN. An increasing frequency of injury discharges was observed at all stages in the pre-saline group, which were suppressed by lidocaine pre-treatment in a dose-dependent manner. Lidocaine pre-treatment also attenuated the number of injury-induced NPY-LI fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, expression of c-Fos-LI neurons in the CN was significantly reduced by an NPY receptor antagonist, indicating that NPY modulated c-Fos expression following MNT. These data suggest that preventing injury discharges with lidocaine pre-treatment can effectively attenuate central sensitization following MNT.

Neuropeptide Y modulates c-Fos protein expression in the cuneate nucleus and contributes to mechanical hypersensitivity following rat median nerve injury.

This study sought to investigate the effects of injury-induced neuropeptide Y (NPY) on c-Fos expression in the cuneate neurons and neuropathic pain after median nerve injury. Four weeks after median nerve transection (MNT), the injured nerves stimulated at low intensity (0.1 mA) expressed significantly less NPY-like immunoreactive (NPY-LI) fibers in the cuneate nucleus (CN) than those stimulated at high intensities (1.0 mA and 10 mA). Conversely, a significantly higher number of c-Fos-LI cells were observed in the CN in rats stimulated with 0.1 mA compared to those stimulated with 1.0 mA or 10 mA. These results suggest that more NPY was released following low-intensity stimulation, and consequently fewer NPY-LI fibers and more c-Fos-LI cells were identified in the CN. Furthermore, the number of c-Fos-LI cells as well as the percentage of c-Fos-LI cuneothalamic projection neurons (CTNs) in the CN was markedly decreased after injection of NPY receptor antagonist along with retrograde tract-tracing method, indicating that NPY regulated c-Fos expression. In rats with median nerve chronic constriction injury (CCI), intracerebroventricular injection of NPY aggravated mechanical allodynia and low-intensity stimulus-evoked c-Fos expression, both of which were reversed by injection of NPY receptor antagonist. However, thermal hyperalgesia was not affected by injection of these two reagents. Taken together, these findings suggest that more NPY release, following low-intensity electrical stimulation of the injured nerve, significantly induces c-Fos expression in the CTNs, which possibly provide the ascending thalamic transmission of neuropathic pain signals.

Characterization of the induced neuropeptide Y-like immunoreactivity in primary sensory neurons following complete median nerve transection.

In this study, we examined characteristics of the neuropeptide Y-like immunoreactive (NPY-LI) dorsal root ganglion (DRG) neurons after complete median nerve transection (CMNT). With fluorogold (FG) injection into normal median nerves, numerous FG-labeled DRG neurons were localized predominantly in the C6 and C7 DRGs, where the focal regions were examined after CMNT. With NPY immunohistochemistry, a few NPY-LI neurons were detected in the ipsilateral but not contralateral DRGs after FG injection into the nerve. As early as 3 days after CMNT a few NPY-LI neurons could be detected, reaching a maximum in the DRGs at 4 weeks, subsiding thereafter over 20 weeks. The NPY-LI DRG neurons were primarily medium-sized and large neurons. With FG injection into the transected median nerve, we found that approximately 99% of NPY-LI neurons were labeled for FG, suggesting that they were derived from the injured but not intact DRG neurons. Using double fluorescent dyes tracing, we detected that some of the injured DRG neurons were NPY-LI neurons that projected to the cuneate nucleus (CN). Following dorsal rhizotomy, our data indicated that after CMNT the induced NPY-LI fibers in the ipsilateral CN originated exclusively from the injured DRG neurons. Taken together, these findings suggest that injury-induced NPY-LI fibers in the CN may originate from the injured DRG neurons via the median primary afferent fibers, affect the excitability of cuneothalamic projection neurons (CTNs), and involve neuropathic sensation following CMNT.