جستجوی مقالات مرتبط با کلیدواژه « neuropathic pain » در نشریات گروه « پزشکی »

Most individuals who suffer from spinal cord injury (SCI) experience neuropathic pain, which currently has no effective treatment. In this study, we examined how testosterone affects neuropathic pain resulting from SCI. 

We administered three different doses of testosterone (4, 8, 16 mg/kg, intraperitoneal) to male rats after an electrolytic lesion of the spinothalamic tract. We then conducted behavioral tests, including open field and von Frey tests, within 28 days post-SCI. On day 28 after SCI, we analyzed spinal tissue using western blot to measure the levels of ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), phospho-extracellular signal-regulated kinase (p-ERK1/2), and p-P38 at the injury site. 

The results showed that testosterone significantly improved both motor activity and mechanical allodynia compared to the SCI-only group. Testosterone also inhibited microglia and astrocyte activation. Furthermore, testosterone significantly decreased p-P38 and p-ERK levels.  

The findings indicate that testosterone may alleviate SCI-induced neuropathic pain by inhibiting the activation of astrocytes and microglia, as well as suppressing MAPK signaling pathways.

Diabetic peripheral neuropathy (DPN) poses a significant threat, affecting half of the global diabetic population and leading to severe complications, including pain, impaired mobility, and potential amputation. The delayed manifestation of diabetic neuropathy (DN) makes early diagnosis challenging, contributing to its debilitating impact on individuals with diabetes mellitus (DM). This review examines the multifaceted nature of DPN, focusing on the intricate interplay between oxidative stress, metabolic pathways, and the resulting neuronal damage. It delves into the challenges of diagnosing DN, emphasizing the critical role played by hyperglycemia in triggering these cascading effects. Furthermore, the study explores the limitations of current neuropathic pain drugs, prompting an investigation into a myriad of pharmaceutical agents tested in both human and animal trials over the past decade. The methodology scrutinizes these agents for their potential to provide symptomatic relief for DPN. The investigation reveals promising results from various pharmaceutical agents tested for DPN relief, showcasing their efficacy in ameliorating symptoms. However, a notable gap persists in addressing the underlying problem of DPN. The results underscore the complexity of DPN and the challenges in developing therapies that go beyond symptomatic relief. Despite advancements in treating DPN symptoms, there remains a scarcity of options addressing the underlying problem. This review consolidates the state-of-the-art drugs designed to combat DPN, highlighting their efficacy in alleviating symptoms. Additionally, it emphasizes the need for a deeper understanding of the diverse processes and pathways involved in DPN pathogenesis.

Neuropathic pain (NP) is the outcome of lesion or disease of the nervous system, and it substantially influences the quality of life. Various inflammatory diseases such as rheumatoid arthritis (RA) and even cancer, may cause NP. Today, treatment of NP is the biggest pharmacological hurdles. Targeting inflammation is a broad task, since many mediators are involved in onset of particular disease. Among these many mediators, the reactive oxygen and nitrogen species generated by macrophages and neutrophils are of great interest because of their major contribution in development of inflammation and NP. This review will concentrate on the pathogenesis of inflammation based on involvement of reactive oxygen and nitrogen species and the activation of signalling cascades in response to oxidative stress. A systematic, and comprehensive search was conducted in the database. Based on the inclusion criteria, more than 300 peer-reviewed publications and 200 articles were chosen. In this review, data on oxidative stress and inflammation is compiled and discussed in the context of chronic neuropathic pain.It is suggested that oxidative stress can activate a variety of pro-inflammatory factors involved in chronic diseases. Animal and clinical evidence suggests that oxidative stress and inflammation linked to overproduction of ROS are highly likely to represent a critical factor for the development of NP in inflammatory diseases.

Regarding the high prevalence of adverse complications of diabetes and the importance of psychological intervention to improve self-care behaviors and adaptive coping styles in diabetic patients, the present study aimed to assess the effectiveness of behavioral activation training on self-care behaviors, perceived pain, and reaction to stress in women with diabetes mellitus type 2. 

The statistical population comprises all women with type 2 diabetes who referred to Neishabur health centers. Thirty women were selected based on a voluntary and convenient sampling method. They were divided randomly into the behavioral activation training group and a control group. They fulfilled the Summary of Diabetes Self-Care Activities, Visual Analog Scale (VAS), and Coping Inventory for Stressful Situations (CISS). We analyzed the data using the descriptive statistics, multivariate covariance analysis test, and SPSS-22 software. 

The results revealed that behavioral activation training improved self-care behaviors (P= 0.001), decreased pain (P= 0.001), increased problem-solving oriented coping to stress (P= 0.001), while it decreased emotion-oriented and avoidant-oriented coping styles (P= 0.001, P= 0.001, respectively) in the experimental group compared to the control group. 

It seems that behavioral activation training improves self-care behaviors, decreases pain, and increases problem-solving-oriented coping to stress in women with type 2 diabetes.

Acorus calamus Linn. from the Acoraceae family exhibits several benefits in neurological disorders but has not been studied for chronic constriction injury (CCI) of median nerve induced neuropathic pain. Damage to median nerve leads to work-related musculoskeletal disorders (WMSDs). this study aimed to assess the effects of the ethanolic root extract of Acorus calamus (EAC) on CCI-induced neuropathic pain and WMSDs in rats.

Animals were randomly divided into 7 groups of 8 animals each. Group 1. Normal control, 2. Sham control, 3. CCI, 4. CCI+ vehicle (CMC), 5. CCI+gabapentin (50 mg/kg), 6. CCI+EAC (20 mg/kg), 7. CCI+EAC (40 mg/kg). On day 0, rats were subjected to the surgical procedure of exposure and ligation of the median nerve-produced CCI at the forearm level. Pain-sensitive tests (i.e., hot plate test, Randall Selitto test), and functional analysis (i.e., walking track) were performed. Total protein, lipid peroxidation, and histopathological changes were also estimated.

CCI significantly increased thermal and mechanical hyperalgesia, raised median functional index (walking track analysis), and induced biochemical and histological disruptions. Oral administration of EAC (40 mg/kg) and gabapentin (50 mg/kg) notably lowered CCI-induced nociceptive pain threshold, improved median nerve functional index, and mitigated tissue histological alterations.

EAC has been found to decrease CCI-induced neuropathic pain of the median nerve. Its mechanisms likely involve neuroprotective, antioxidant, and anti-inflammatory properties.

Neuropathic pain is a common and painful somatosensory nervous system disease, and its treatment remains a medical challenge. Evidence demonstrates that gut microbiota alters in neuropathic pain and, therefore, improvement of the gut flora may affect the disease. The present study aimed to evaluate the antinociceptive effect of probiotics in neuropathic pain and oxidative biomarkers’ responsiveness to the probiotic treatment.

Using chronic constriction injury (CCI) of the rats' sciatic nerve, neuropathic pain was induced. Investigating the analgesic effect of the probiotics mixture, 40 male rats were randomly assigned to 4 groups (n=10 for each): Sham-operated (SM), and CCI model rats orally received 1 mL saline (CS), or 100 mg/kg gabapentin (CG) or 1 mL probiotics mixture (CP) Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (109 CFU of each) daily. Using behavioral tests, the pain was assessed on days 1, 4, 7, 14, and 21 of the study. Finally, the biochemical evaluation of sciatic nerve tissue was done.

Probiotics decreased cold and mechanic allodynia and thermal hyperalgesia. Reducing lipid peroxidation levels and increasing total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were also significant in the probiotics group.

These findings suggest that probiotics have analgesic effects on the CCI model of neuropathic pain via increasing the antioxidant capacity of the rats’ sciatic nerve.

 Painful diabetic polyneuropathy (P-DPN) occurs in 20% - 30% of diabetic patients. Currently, therapeutic strategies include lifestyle modifications, good glycemic control, and neuropathic pain drugs. Spinal cord stimulation (SCS) has been shown to be successful in patients who have not responded to other treatments. The American Diabetes Association strongly recommends early screening and diagnosis for this condition through clinical tests and nerve conduction study (NCS). In recent years, high-resolution ultrasonography (HRUS) with the analysis of cross-sectional area (CSA) has shown an increasingly important role in detecting changes in the nervous structures, blood vessels, echo, and mobility of the nerve. Cross-sectional area is frequently enlarged in these patients, even those with normal NCS. We aimed to use SCS with fast-acting sub-perception therapy (FAST) modality to treat P-DPN. We also evaluated the CSA of the involved nerves before and after treatment.

 A 58-year-old female patient was referred to our hospital in 2020 (Civitavecchia, Italy). She suffered from P-DPN for 3 years and did not respond to conventional medical treatments. Preoperative electromyography (EMG) was negative for radiculopathy, while electroneurography (ENG) showed a reduction in sensory conduction velocity (SCV) in the sural nerve (SN) bilaterally. Clinical tests on perceived pain and quality of life showed high severity. The report was confirmed by HRUS with enlargement of the CSA of the posterior tibial nerve (PTN), external popliteal nerve (EPN), and SN. The patient was successfully subjected to all-in-one SCS implantation in the FAST modality. She obtained immediate pain relief that remained unaltered at the 3-month follow-up. The patient completely discontinued drug therapy. One month after implantation, ENG highlighted an increased SN SCV, and the HRUS of PTN EPN and SN showed a significant reduction in CSA in all 3 nerves involved.

 Early diagnosis and treatment are crucial in improving the clinical outcome of P-DPN, but there is still no gold standard therapy. Spinal cord stimulation in the new FAST modality was effective in this clinical case. The pain relief was supported by a significant reduction in the CSA of the studied nerves observed on HRUS 1 month after SCS implantation. The results and the improvement of a pathological nervous pattern, albeit with a short follow-up of only 3 months, could suggest not only a symptomatic but perhaps also a therapeutic role of SCS in P-DPN.

Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.

Traditionally, Nigella sativa L. has been known as a medical intervention to treat numerous diseases. This study aimed at investigating the antihyperalgesic effect of black seed oil (BSO) in an experimental model of neuropathic pain.

Chronic constriction injury (CCI) was performed under anesthesia. The sciatic nerve was ligated with four loose ties. Two separate protocols were used to administer BSO. In chronic treatment, rats were given daily doses of BSO (250, 500, and 1000 mg/kg p.o.) from the 1st day until the 21st post-CCI day. While, in acute treatment, BSO (250, 500, and 1000 mg/kg p.o.) was administered only on the 7th, 14th, and 21st days. CCI and sham groups were given almond oil according to the same schedule. Behavioral scores were determined by evaluation of the paw withdrawal in the plantar, Von Frey, and acetone tests, on the 7th, 14th, and 21st days.

Our results showed that CCI leads to significant allodynia and hyperalgesia in the ipsilateral paw after surgery. Chronic administration of BSO (500 and 1000 mg/kg) obviously attenuated heat hyperalgesia and mechanical allodynia. However, daily administration of BSO did not alter cold allodynia. Nevertheless, when BSO was administered, 30 min before the pain assessment tests, hypersensitivity was not improved in the treated animals.

These results demonstrated BSO can inhibit neuropathic pain progression and suggests a potential use of BSO to manage hyperalgesia and allodynia. However, additional research is necessary to approve BSO effectiveness, in neuropathic pain conditions.

Over the last several decades, opioid diversion, misuse, and over-prescription have run rampant in the United States. Spinal cord stimulation (SCS) has been FDA approved for treatment for a primary indication of neuropathic limb pain that is resistant to more conservative medical therapy. The disorders qualified for treatment include neuropathic, post-surgical, post-amputation, osteodegenerative, and pain related to vascular disease. Some of the most frequently cited conditions for treatment of SCS include failed back surgery syndrome, complex regional pain syndrome (CRPS) Type I and Type II, and post-herpetic neuralgias. Developments in SCS systems have led to the differentiation between the delivered electromechanical waveform patterns, including tonic, burst, and high-frequency. Burst SCS mitigates traditional paresthesia due to expedited action potential and offers improved pain relief. Burst SCS has been shown in available studies to be non-inferior to the traditional SCS, which can cause pain paresthesia in patients who already have chronic pain. Burst SCS does not seem to cause or need the paresthesia seen in traditional SCS, making SCS not tolerable to patients. Moreover, some studies suggest that burst SCS may decrease opioid consumption in patients with chronic pain. This can make burst SCS an extremely useful tool in the battle against chronic pain and the raging opioid epidemic. As of now, more research needs to be performed to further delineate the effectiveness and long-term safety of this device.