Combined effect of Cerium oxide nanoparticles loaded scaffold and photobiomodulation therapy on pain and neuronal regeneration following spinal cord injury: an experimental study.

BACKGROUND: Spinal cord injury (SCI) remained one of the challenges to treat due to its complicated mechanisms. Photobiomodulation therapy (PBMT) accelerates neuronal regeneration. Cerium oxide nanoparticles (CeONPs) also eliminate free radicals in the environment. The present study aims to introduce a combined treatment method of making PCL scaffolds as microenvironments, seeded with CeONPs and the PBMT technique for SCI treatment. METHODS: The surgical hemi-section was used to induce SCI. Immediately after the SCI induction, the scaffold (Sc) was loaded with CeONPs implanted. PBMT began 30 min after SCI induction and lasted for up to 4 weeks. Fifty-six male rats were randomly divided into seven groups. Glial fibrillary acidic protein (GFAP) (an astrocyte marker), Connexin 43 (Con43) (a member of the gap junction), and gap junctions (GJ) (a marker for the transfer of ions and small molecules) expressions were evaluated. The behavioral evaluation was performed by BBB, Acetone, Von Frey, and radiant heat tests. RESULT: The SC + Nano + PBMT group exhibited the most remarkable recovery outcomes. Thermal hyperalgesia responses were mitigated, with the combined approach displaying the most effective relief. Mechanical allodynia and cold allodynia responses were also attenuated by treatments, demonstrating potential pain management benefits. CONCLUSION: These findings highlight the potential of PBMT, combined with CeONPs-loaded scaffolds, in promoting functional motor recovery and alleviating pain-related responses following SCI. The study underscores the intricate interplay between various interventions and their cumulative effects, informing future research directions for enhancing neural repair and pain management strategies in SCI contexts.

Evaluation of epigenetic (HDAC, DNMT) and pain (Gad65, TGF) factors following photobiomodulation therapy in a neuropathic pain model.

Photobiomodulation therapy (PBMT) is converted to the most common analgesic treatment before the whole mechanism is yet to be discovered. This study for the first time was designed to investigate alternations of epigenetic factors after pain and PBMT. The CCI model was chosen to induce pain. Pain evaluation tests including plantar, acetone, von Frey, and pinch were done weekly. Then spinal cord tissue was isolated for evaluating mRNA expression of DNMT3a, HDAC1, and NRSF using RT-qPCR method, and protein expression factors of HDAC2 and DNMT3a using western blotting. GAD65 and TGF-ß proteins were assessed by the IHC method. PBMT increased the pain threshold up to the point where it roughly met the pain threshold of the control group. After three weeks of treatment, both PBMT protocols demonstrated a reduction in allodynia and hyperalgesia. While some molecules, such as TGF-ß and Gad65, increased following PBMT, we observed no inhibition of NRSF, HDAC1, and DNMT3a expression despite implementing two different protocols.

Evaluation of photobiomodulation therapy (117 and 90s) on pain, regeneration, and epigenetic factors (HDAC 2, DNMT3a) expression following spinal cord injury in a rat model.

BACKGROUND: Photobiomodulation therapy (PBMT), due to its anti-inflammatory, analgesic effects, and most importantly as a non-invasive procedure, has currently gained a special setting in pain relief and the treatment of Spinal cord injuries (SCI). However, the mechanism of action of the PBM is not yet completely understood. METHODS: In this study, SCI is induced by an aneurysm clip, and PBM therapy was applied by a continuous-wave (CW) laser with a wavelength of 660 nm. Adult male rats were divided into four groups: Control, SCI, SCI + PBMT 90s, and SCI + PBMT 117s. After 7 weeks, hyperalgesia, allodynia, and functional recovery were assessed. Fibroblasts infiltrating the spinal cord were counted after H&E staining. The expression of epigenetic factors (HDAC2, DNMT3a), protein relevant for pain (GAD65), and astrocytes marker (GFAP) after 4 weeks of daily PBMT (90 and 117s) was probed by western blotting. RESULTS: Both PBMTs (90 and 117s) significantly improved the pain and ability to move and fibroblast invasion was reduced. SCI + PBMT 90s, increased GAD65, HDAC2, and DNMT3a expression. However, PBMT 117s decreased GFAP, HDAC2, and DNMT3a. CONCLUSION: PBMT 90 and 117s improved the pain, and functional recovery equally. The regulation of epigenetic mechanisms appears to be a significant effect of PBMT117s, which emphasizes on impact of radiation duration and accumulative energy.

Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats.

Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction.

Radiosensitising effect of iron oxide-gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting.

Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio-sensitising effect of gold-coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold-coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold-coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold-coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay blood test were also performed. Gold-coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.

The effect of gabapentin and pregabalin administration on memory in clinical and preclinical studies: a meta-analysis and systematic review.

BACKGROUND: Today, gabapentinoids such as Gabapentin (GBP) and pregabalin (PGB) are widely used as painkillers. This may alter the function of the nervous system; hence their results may include a difference in memory and processes that end in memory formation. This study aims to conclude whether gabapentinoids can alter memory or not by reviewing and analyzing clinical and preclinical studies. MATERIAL AND METHODS: A comprehensive search was carried out in databases including PUBMED, EMBASE, SCOPUS, and Web of Science. In the included studies, memory was measured as an outcome variable in clinical or preclinical studies. RESULT: A total of 21 articles (4 clinical, 17 preclinical) were included in the meta-analysis by STATA Software. The results showed that memory changes under the influence of GBP. Both the administrated dosage and the time of administration are important in the final results and latency time of retention. GBP administration in healthy animals increased latency time, whereas if the administration of GBP took place exactly before training, the latency time increased slightly. Short-term administration of PGB in healthy volunteers is accompanied by transient side effects on the CNS. However, the number and homogeneity of the studies were not such that a meta-analysis could be performed on them. CONCLUSION: Clinical and preclinical studies showed that PGB administration did not confirm its improving memory effect. GBP administration in healthy animals increased latency time and improved memory. Although it depended on the time of administration.

Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO2) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthesized, and a gelatin solution containing cerium oxide nanoparticles was attached to the scaffold. For the animal study, 40 male Wistar rats were randomly divided into 4 groups (n = 10): (a) Control; (b) Spinal cord injury (SCI); (c) Scaffold (SCI + scaffold without CeO2 nanoparticles); (d) Scaffold-CeO2 (SCI + scaffold containing CeO2 nanoparticles). After creation of a hemisection SCI, scaffolds were placed at the site of injury in groups c and d, and after 7 weeks the rats were subjected to behavioral tests and then sacrificed for preparation of the spinal cord tissue to measure the expression of G-CSF, Tau and Mag proteins by Western blotting and Iba-1 protein by immunohistochemistry. The result of behavioral tests confirmed motor improvement and pain reduction in the Scaffold-CeO2 group compared to the SCI group. Decreased expression of Iba-1 and higher expression of Tau and Mag in the Scaffold-CeO2 group compared to the SCI group could be the result of nerve regeneration caused by the scaffold containing CeONPs as well as relief of pain symptoms.

Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis.

OBJECTIVE: About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis. METHODS: The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles. RESULTS: The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1-3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity. CONCLUSION: AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

Optimization of the Duration and Dose of Photobiomodulation Therapy (660 nm Laser) for Spinal Cord Injury in Rats.

Objective: Spinal cord injury (SCI) causes motor deficits, urinary incontinence, and neuropathic pain. This study was designed to optimize a photobiomodulation therapy (PBMT) protocol using a continuous wave (CW) 660 nm laser in rats with SCI. Specifically, the number of days of irradiation and the daily dose of PBMT were investigated. Methods: The study was performed in two steps. In the first step, a comparison between the effects of PBMT (45 sec) daily for 2 and 4 weeks on pain and movement [Basso, Beattie, and Brenham (BBB) score] was made. In the second step, a comparison between different durations of irradiation (27, 45, 90, and 117 sec) was performed. PBMT used a 100 mW laser delivered to 9 points on and around the lesion site. Oxidative stress, fibroblast invasion, and time to achieve spontaneous urination were also assessed. Results: The improvement in movement and pain stopped with discontinuation of radiation at week 2 and fibroblast invasion resumed. No improvement was seen in movement and pain in the group receiving PBMT for 27 sec compared with the groups receiving higher doses of laser radiation. Animals receiving 117 sec of photobiomodulation showed a higher BBB score even in the first 3 days. Conclusions: The number of days is an important factor for improving mobility; however, the daily dose of radiation is more important for pain relief.

Injection of Cerium Oxide Nanoparticles to Treat Spinal Cord Injury in Rats.

This study investigated the effects of local injection of cerium oxide nanoparticles (CeONPs) in a rat spinal cord injury (SCI) model. Thirty-six adult male Wistar rats were divided into 4 groups: controls (healthy animals), sham (laminectomy), SCI (laminectomy+SCI induction), and treatment (laminectomy+SCI induction+intrathecal injection of CeONPs immediately after injury). SCI was induced using an aneurysm clip at the T12-T13 vertebral region. Motor performance and pain threshold tests were performed weekly; H&E staining and measurement of cavity sizes were performed 6 weeks after injury. The expression of granulocyte colony-stimulating factor (GCSF), P44/42 MAPK, P-P44/42 MAPK, Tau, myelin-associated glycoprotein(MAG) was evaluated after 6 weeks by Western blot. The Basso, Beattie, and Bresnahan locomotor scoring scales improved in animals receiving CeONPs compared with SCI animals. The cavity sizes were less in the treatment group. GCSF expression was similar in the animals receiving CeONPs compared with the SCI group but the expression of ERK1/ERK2 and phospho-ERK was lower than in the SCI group. Expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group. These data indicate that the use of CeONPs may improve motor functional recovery in SCI.

Mechanistic aspects of photobiomodulation therapy in the nervous system.

Photobiomodulation therapy (PBMT) previously known as low-level laser therapy (LLLT) has been used for over 30 years, to treat neurological diseases. Low-powered lasers are commonly used for clinical applications, although recently LEDs have become popular. Due to the growing application of this type of laser in brain and neural-related diseases, this review focuses on the mechanisms of laser action. The most important points to consider include the photon absorption by intracellular structures; the effect on the oxidative state of cells; and the effect on the expression of proteins involved in oxidative stress, inflammation, pain, and neuronal growth.

Will carbon nanotube/nanofiber bring new hope for the treatment of heart damage? A systematic review.

Aim: Despite scientific advances, the number of cardiovascular patients is increasing worldwide. To protect damaged cardiomyocytes from further harm, novel and safer approaches are needed to help regeneration and prevent fibrosis. Methods: In this study, we performed a systematic review of in vitro and preclinical studies of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) for help to treat heart damage. Conclusion: CNTs/CNFs in hydrogels cause higher conductivity, and the in case of alignment this increase is more than the random state. CNTs/CNFs can improve structural specification of the hydrogel for cardiac cell proliferation and enhance expression of genes associated with final differentiation of various stem cells to cardiac cells.

Despite scientific advances, the number of cardiovascular patients is increasing worldwide, and unfortunately, no solution has been provided to protect patients from further damage after ischemia. The heart, unlike many tissues in the human body, lacks the ability to regenerate after damage. To protect damaged heart cells from further damage as well as to grow new heart cells, newer and safer approaches are needed to help reconstruction. In this study, we conducted a systematic review of in vitro studies and animal models of heart attack that have used carbon nanotubes and carbon nanofibers to treat heart damage. The results showed these nanomaterials increase the conductivity of the material in which they are mixed and change the structural characteristics in a way that increases the proliferation of heart cells and causes the differentiation into cardiac cells. It also helps to repair the damaged area of the heart after myocardial ischemia.

Chondroitinase ABC Administration in Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis.

Introduction: The present systematic review and meta-analysis aims to conduct a comprehensive and complete search of electronic resources to investigate the role of administrating Chondroitinase ABC (ChABC) in improving complications following Spinal Cord Injuries (SCI). Methods: MEDLINE, Embase, Scopus, and Web of Sciences databases were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using the STATA 14.0 software, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 34 preclinical studies were included. ChABC administration improves locomotion recovery after SCI (SMD=0.90; 95% CI: 0.61 to 1.20; P<0.001). The subgroup analysis showed that the differences in the SCI model (P=0.732), the severity of the injury (P=0.821), the number of ChABC administrations (P=0.092), the blinding status (P=0.294), the use of different locomotor score (P=0.567), and the follow-up duration (P=0.750) have no effect on the efficacy of ChABC treatment. Conclusion: The findings of the present study showed that prescribing ChABC has a moderate effect in improving locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as adjuvant therapy and not as primary therapy.

Pain Alleviating Effect of Adipose-Derived Stem Cells Transplantation on the Injured Spinal Cord: A Behavioral and Electrophysiological Evaluation.

Few studies are conducted on the efficacy of human adipose-derived stem cells (ADSCs) in spinal cord injury (SCI) management and electrophysiological changes in the spinal cord. Therefore, the present study aimed to determine the effect of ADSCs on neuropathic pain, motor function recovery, and electrophysiology assessment. For the purpose of this study, adult male Wistar rats (weight: 140-160 gr, n = 42) were randomly allocated into five groups namely intact animals, sham-operated, SCI non-treated animals, vehicle-treated (culture media), and ADSCs treated groups. One week after clips compression SCI induction, about 1×106 cells were transplanted into the spinal cord. As well, both neuropathic pain (allodynia and hyperalgesia) and motor function were measured weekly. Cavity size, ADSCs survival, and electrophysiology assessments were measured at the end of the eighth week. The transplantation of ADSCs resulted in a significant improvement in the locomotion of SCI animals (p<0.0001), mechanical allodynia (p<0.0001), cold allodynia (p<0.0001), mechanical hyperalgesia (p<0.0001), and thermal hyperalgesia (p<0.0001). The cavity size was significantly smaller among the ADSCs-treated animals (p <0.0001). The single-unit recording showed that the transplantation of ADSCs decreased wide dynamic range (WDR) in neurons and it evoked potential in response to receiving signals from Aß (p<0.0001) and Aδ (p=0.003) C-fiber (p<0.0001) neurons. Post-discharge recorded from WDR neurons decreased after the transplantation of ADSCs (p<0.0001) and wind up in the ADSCs-treated group was lower than that of the SCI group (p=0.003). Our results showed that the transplantation of ADSCs could significantly alleviate neuropathic pain, enhance motor function recovery, and improve electrophysiology findings after SCI.

The Toxic Effect of Silver Nanoparticles on Nerve Cells: A Systematic Review and Meta-Analysis.

Despite the increasing use of silver nanoparticles in medical sciences, published studies on their interaction with nerve cells and evaluation of risks are dispersed. This systematic review and meta-analysis could be used to devise safety guidelines for the use of silver nanoparticles in industry and medicine to reduce adverse effects on the CNS.After extensive searches, the full text of 30 related studies was reviewed and data mining completed. Data were analyzed by calculating the mean of different ratios between treated and untreated groups. Linear regression between variables was evaluated by meta-regression. Subgroup analysis was also performed due to heterogeneity.Treatment with silver nanoparticles significantly reduced cell viability (SMD = -1.79%; 95% CI: -2.17 to -1.40; p < 0.0001). Concentration > 0.1 µg/mL could kill neurons, while lower concentration would not (SMD -0.258; 95% CI: -0.821 to 0.305; p = 369). In addition to the concentration, the coating, size of the nanoparticles, and cell type are also factors that influence SNP nerve cell toxicity. Measurement of apoptosis (SMD = 2.21; 95% CI: 1.62 to 2.80; p=0.001) and lactate dehydrogenase release rate (SMD = 0.9; 95% CI: 0.33 to 1.47; p < 0.0001) also confirmed the destructive effect of silver nanoparticles on nerve cells.

Distribution of gold nanoparticles into the brain: a systematic review and meta-analysis.

Despite the widespread use of gold nanoparticles (GNPs), there is no consensus on their distribution to different tissues and organs. The present systematic review and meta-analysis addresses the accumulation of GNPs in brain tissue. Extensive searches were conducted in electronic databases, Medline, Web of Science, EMBASE, and Scopus. Based on inclusion and exclusion criteria, primary and secondary screening was performed. The value of brain accumulation of gold nanoparticle (the percentage of the injection dose of GNPs/gram of brain tissue that applied as effect size (ES) in analysis) and the standard error of the mean were extracted from articles and analyzed by calculating the pooled ES and the pooled confidence interval (CI) using STATA software. p ≤ 0.05 was considered significant. Thirty-eight studies were included in the meta-analysis. The results showed that the amount of GNPs was 0.06% of the injection dose/gram of brain tissue (ES = 0.06, %95 CI: 0.06-0.06, p < 0.0001). Considering the time between injection and tissue harvest (follow-up time), after 1 h the GNPs in brain tissue was 0.288% of the injection dose/gram of tissue (ES = 0.29, 95% CI: 0.25-0.33, p < 0.0001), while after four weeks it was only 0.02% (ES = 0.02, 95% CI: 0.01-0.03, p < 0.0001) of the injection dose/gram of tissue. The amount of GNPs in brain tissue was higher for PEG-coated GNPs compared to uncoated GNPs, and it was 5.6 times higher for rod-shaped GNPs compared to spherical GNPs. The mean amount of GNPs in the brain tissues of animals bearing a tumor was 5.8 times higher than in normal animals.

Chronic nanocurcumin treatment ameliorates pain-related behavior, improves spatial memory, and reduces hippocampal levels of IL-1ß and TNFα in the chronic constriction injury model of neuropathic pain.

BACKGROUND: Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. METHODS: Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1ß, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1ß (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. CONCLUSION: Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1ß and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity.

Platelet-rich plasma in umbilical cord blood reduces neuropathic pain in spinal cord injury by altering the expression of ATP receptors.

BACKGROUND: Neuropathic pain following injury or dysfunction of the peripheral or CNS is one of the most important medical challenges to treat. Humane platelet-rich plasma (HPRP), which is a rich source of growth factors, may be able to treat and reduce pain caused by spinal cord injury (SCI). In this study, the effect of HPRP on neuropathic pain caused by SCI was investigated. METHODS: Sixty adult male Wistar rats were randomly divided into 6 groups: control, sham, SCI, vehicle (SCI+platelet-poor plasma), SCI+ PRP2day (injection 48 hrs after SCI) and SCI+PRP14day (injection 14 days after SCI). SCI was induced at the T12-T13 level. Behavioral tests were conducted weekly after injury for six weeks. Allodynia and hyperalgesia were assessed using acetone drops, plantar test and von Frey filament. Cavity size and the number of fibroblasts were determined by H&E stain, and the expression of mTOR, p-mTOR, P2×3R and P2Y4R were determined using the western blot technique. Data were analyzed using PRISM & SPSS software. RESULTS: PRP injection showed a higher pain threshold in mechanical allodynia (p<0.0001), cold allodynia (p<0.0001) and thermal hyperalgesia (p<0.0001) than those in the spinal. Animals treated with PRP also reduced cavity size, fibroblast number, p-mTOR/mTOR ratio, and P2×3R expression, and increased P2Y4R expression. The difference between the two groups was not statistically significant. CONCLUSIONS: The results showed that PRP reduced SCI-induced allodynia and hyperalgesia by regulating ATP signaling. Using HPRP can open a new window in the treatment of pain caused by damage to the nervous system.

The effect of chondroitinase ABC and photobiomodulation therapy on neuropathic pain after spinal cord injury in adult male rats.

INTRODUCTION: . The goal of the study was to test the effects of photobiomodulation therapy (PBMT) and intra-spinal injection of chondroitinase ABC (chABC) both alone and combined on pain induced by spinal cord injury (SCI) in rats. MATERIAL AND METHODS: SCI was induced by compression using an aneurysm clip. PBMT used a 660 nm laser starting at 30 minutes after SCI and then daily for 2 week, and at the end of 1-week ChABC was injected into the spinal cord. Allodynia (mechanical and cold), hyperalgesia (mechanical and thermal) and functional recovery were measured. Molecular levels of IL6, BDNF, GDNF and Gad65 were evaluated. RESULTS: . Both ChABC, PBMT and the combination reduced allodynia and thermal hyperalgesia and improved functional recovery, but did not reduce mechanical hyperalgesia. Pain-related factors (BDNF and IL6) were decreased and anti-nociceptive factors (Gad65 and GDNF) were increased. CONCLUSION: . Treatment of SCI by PBM is a non-invasive technique, and could be improved by ChABC injection to reduce neuropathic pain and improve movement.