Treatment Of Neuropathic Pain Research Articles

HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments.

Explorations of Agonist Selectivity for the α9* nAChR with Novel Substituted Carbamoyl/Amido/Heteroaryl Dialkylpiperazinium Salts and Their Therapeutic Implications in Pain and Inflammation.

There is an urgent need for nonopioid treatments for chronic and neuropathic pain to provide effective alternatives amid the escalating opioid crisis. This study introduces novel compounds targeting the α9 nicotinic acetylcholine receptor (nAChR) subunit, which is crucial for pain regulation, inflammation, and inner ear functions. Specifically, it identifies novel substituted carbamoyl/amido/heteroaryl dialkylpiperazinium iodides as potent agonists selective for human α9 and α9α10 over α7 nAChRs, particularly compounds 3f, 3h, and 3j. Compound 3h (GAT2711) demonstrated a 230 nM potency as a full agonist at α9 nAChRs, being 340-fold selective over α7. Compound 3c was 10-fold selective for α9α10 over α9 nAChR. Compounds 2, 3f, and 3h inhibited ATP-induced interleukin-1β release in THP-1 cells. The analgesic activity of 3h was fully retained in α7 knockout mice, suggesting that analgesic effects were potentially mediated through α9* nAChRs. Our findings provide a blueprint for developing α9*-specific therapeutics for pain.

Surgical Treatment of Neuropathic Chronic Postherniorrhaphy Inguinal Pain: A Systematic Review and Meta-Analysis

Background/Objectives: Neuropathic chronic postherniorrhaphy inguinal pain (CPIP) is a serious adverse outcome following inguinal hernia repair surgery. The optimal surgical treatment for neuropathic CPIP remains controversial in the current literature. This systematic review aims to evaluate the effectiveness of various surgical techniques utilized to manage neuropathic CPIP. Methods: The electronic databases Medline, Embase, Web of Science, Cochrane Central, and Google Scholar were searched. Inclusion criteria were defined to select studies reporting on the efficacy of surgical interventions in patients with neuropathic CPIP. The primary outcome was postoperative pain relief, as determined by postoperative numerical or nonnumerical pain scores. Results: Ten studies met the inclusion criteria. Three surgical techniques were identified: selective neurectomy, triple neurectomy, and targeted muscle reinnervation. Proportions of good postoperative results of the surgical techniques ranged between 46 and 88 percent. Overall, the surgical treatment of neuropathic CPIP achieved a good postoperative result in 68 percent (95% CI, 49 to 82%) of neuropathic CPIP patients (n = 244), with targeted muscle reinnervation yielding the highest proportion of good postoperative results. Conclusions: The surgical treatment of neuropathic CPIP is generally considered safe and has demonstrated effective pain relief across various surgical techniques. Targeted muscle reinnervation exhibits considerable potential for surpassing current success rates in inguinal hernia repair surgery.

The efficacy of botulinum toxin in neuropathic pain: a systematic review

Introduction Neuropathic pain (NP) is characterised as a lesion or disease directly affecting the somatosensory system. This study aims to analyse the efficacy of botulinum toxin type A (BT-A) in the treatment of neuropathic pain. Methods This systematic literature review, guided by PRISMA, applied the PICO strategy with the following criteria: (P = patients with neuropathic pain, I = botulinum toxin, C = placebo or active drug, and O = pain relief). Results Fourteen articles, all randomised controlled trials with a placebo control, were included in the review. A total of 645 patients were randomised, with 353 patients receiving treatment with botulinum toxin type A in doses ranging from 25U to 400U. The evaluated studies addressed trigeminal neuralgia, diabetic polyneuropathy, post-herpetic neuralgia, spinal cord injury, phantom limb pain, and peripheral neuropathic pain after trauma or surgery. Conclusion BT-A has emerged as a promising treatment for various origins of neuropathic pain. Therefore, future studies should adopt stricter criteria regarding dosage and routes of administration to ensure effective and consistent BT-A application.

Chinese expert consensus on the surgical treatment of neuropathic pain by the spinal cord dorsal root entry zone

In order to promote the standardization of the treatment of neuropathic pain by spinal dorsal root entry surgery, alleviate the pain of certain specific neuropathic pain patients, and improve their quality of life and survival, experts with experience in neuropathic pain and spinal dorsal root entry surgery were organized by Functional Neurosurgery Group of the Neurosurgery Branch of the Chinese Medical Association and Functional Neurosurgery Expert Committee of Chinese Congress of Neurological Surgeons to write this consensus. Based on a systematic review and summary of literature and clinical evidence at home and abroad, this consensus discusses the diagnosis and drug treatment of neuropathic pain, clinical application of, spinal dorsal root entry surgery the selection of patients receiving surgery of dorsal root entry zone, preoperative examination, surgical procedures, postoperative management, and the prevention and management of postoperative complications, and forms 12 recommended recommendations, providing reference and guidance for clinical work on the treatment of neuropathic pain through spinal dorsal root entry surgery.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Peripheral Nerve Stimulation of the Shoulder: A Technical Primer.

Scapulalgia or shoulder pain accounts for 16% of all musculoskeletal complaints in the healthy adult population and becomes more common as we age. When this pain exceeds 3 months in duration, it is deemed to be chronic, and typically treated in an escalating manner. Spanning a continuum of conservative and non-conservative measures, chronic shoulder pain treatments range from rest and physical therapy to surgery. Since each patient presents with a unique spectrum of symptoms a customized treatment plan is often required. Over the lifetime of many of these patients, a variety of treatment options are required. One of these treatment options, peripheral nerve stimulation (PNS), is a minimally invasive procedure in which an electrical impulse is delivered through a percutaneously implanted, small caliber electrode to a peripheral nerve proximal to the lesion which interferes with the pain signals. Over the past several years, significant growth of PNS in the treatment of chronic neuropathic pain has been observed. However, the procedural techniques have not been well described. The foundation of long-term, minimally invasive percutaneous PNS in patients with chronic shoulder pain, and procedural techniques for stimulating the suprascapular and axillary nerves using fluoroscopy or ultrasonography will be described in this report.

Analgesic candidate adenosine A3 receptors are expressed by perineuronal peripheral macrophages in human dorsal root ganglion and spinal cord microglia.

Adenosine receptors are a family of purinergic G protein-coupled receptors that are widely distributed in bodily organs and in the peripheral and central nervous systems. Recently, antihyperalgesic actions have been suggested for the adenosine A3 receptor, and its agonists have been proposed as new neuropathic pain treatments. We hypothesized that these receptors may be expressed in nociceptive primary afferent neurons. However, RNA sequencing across species, eg, rat, mouse, dog, and human, suggests that dorsal root ganglion (DRG) expression of ADORA3 is inconsistent. In rat and mouse, Adora3 shows very weak to no expression in DRG, whereas it is well expressed in human DRG. However, the cell types in human DRG that express ADORA3 have not been delineated. An examination of DRG cell types using in situ hybridization clearly detected ADORA3 transcripts in peripheral macrophages that are in close apposition to the neuronal perikarya but not in peripheral sensory neurons. By contrast, ADORA1 was found primarily in neurons, where it is broadly expressed at low levels. These results suggest that a more complex or indirect mechanism involving modulation of macrophage and/or microglial cells may underlie the potential analgesic action of adenosine A3 receptor agonism.

Efficacy of pregabalin, amitriptyline, and gabapentin for neuropathic pain

Neuropathic pain largely influences the well-being of patients. Anticonvulsant and antidepressant medications, such as Pregabalin, Gabapentin, and Amitriptyline, are routinely prescribed as initial treatments for neuropathic pain. The study sample has a total of 270 patients who meet the inclusion criteria and are further distributed into three equally sized groups (A, B, and C). Group A was administered with Gabapentine 300mg, Group B with Pregabalin 75 mg, and Amitriptyline 10 mg to Group C. The occurrence of any adverse drug response was documented using the ADR reporting form, while the pain of the patient's post-medication was recorded using a numerical pain rating scale (NPRS). The comparison of the NPRS scores of all three groups "by using ANOVA test" both at baseline and after 15 days reveal that the differences between the three groups are statistically insignificant (p > 0.089). However, after one month of continuous use, the difference becomes slightly significant (I.e., p = 0.003). Gabapentin, pregabalin, and amitriptyline demonstrate similar effectiveness in alleviating neuropathic (NeP) pain. The study concludes that gabapentin is superior to both pregabalin and amitriptyline with fewer adverse effects, leading to improved patient adherence for long-term use.

Synthesis and SAR investigation of biphenylaminoquinoline derivatives with benzyloxy substituents as promising anticancer agents.

The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the meta or para position of the biphenyl ring categorized into two distinct groups: [4,3']biphenylaminoquinoline-substituted and [3,3']biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure-activity relationship. Furthermore, we determined the IC50 values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3']biphenylaminoquinoline derivative 7j displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC50 values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3']biphenylaminoquinoline 7j for further investigation as a prospective anticancer agent in future research endeavors.

Design of Mixed Medicinal Plants, Rich in Polyphenols, Vitamins B, and Palmitoylethanolamide-Based Supplement to Help Reduce Nerve Pain: A Preclinical Study.

Neuropathy affects 7-10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.

Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain.

Blood-derived preparations, including autologous or allogenic serum, umbilical cord serum/plasma, and platelet-rich plasma eye drops, contain various growth factors, cytokines, and immunoglobulins that resemble natural tears. These components play important roles in corneal cell migration, proliferation, and wound healing. Blood-derived eye drops have demonstrated clinical effectiveness across a spectrum of ocular surface conditions, encompassing dry eye disease, Sjögren's syndrome, graft-versus-host disease, and neuropathic corneal pain (NCP). Currently, management of NCP remains challenging. The emergence of blood-derived eye drops represents a promising therapeutic approach. In this review, we discuss the benefits and limitations of different blood-derived eye drops, their mechanisms of action, and treatment efficacy in patients with NCP. Several studies have demonstrated the clinical efficacy of autologous serum eye drops in relieving pain and pain-like symptoms, such as allodynia and photoallodynia. Corneal nerve parameters were also significantly improved, as evidenced by increased nerve fiber density, length, nerve reflectivity, and tortuosity, as well as a decreased occurrence of beading and neuromas after the treatment. The extent of nerve regeneration correlated with improvement in patient-reported photoallodynia. Cord plasma eye drops also show potential for symptom alleviation and corneal nerve regeneration. Future directions for clinical practice and research involve standardizing preparation protocols, establishing treatment guidelines, elucidating underlying mechanisms, conducting long-term clinical trials, and implementing cost-effective measures such as scaling up manufacturing. With ongoing advancements, blood-derived eye drops hold promise as a valuable therapeutic option for patients suffering from NCP.

FIXED DOSE COMBINATION OF MECOBALAMIN AND PREGABALIN IN THE TREATMENT OF OROFACIAL NEUROPATHIC PAIN

Introduction: orofacial neuropathic pain is extraordinary disease in character with its complicated management. Mecobalamin has been used to provide regeneration of traumatized nerves. Pregabalin with its analgesic activities relieves the clinical signs of neuropathic pain. The aim of this case report is to explain fixed dose combination of Mecobalamin and Pregabalin as the treatment of neuropathic pain caused by inferior alveolar nerve and facial nerve neuropathy. Case: First case was an inferior alveolar nerve neuropathy experienced by 63 years old female with complaints of persistent pain and numbness around the left chin and left lower lip the day following the procedure of surgery for the treatment of dentoalveolar abscess on left second premolar of mandibula. Second case was facial nerve neuropathy experienced by 54 years old female had persistent pain and numbness of the anterior two-thirds of the tongue after total thyroidectomy and 1,100 MBq (30 mCi) activity of Radioactive iodine (RAI) therapy, followed with two 131I whole body scans. Case Management: Mecobalamin 500 µg and Pregabalin 75 mg twice daily for 5 weeks were given with tolerable side effects and improvement symptoms. Discussion: Pregabalin combined with Mecobalamin can reduce orofacial neuropathic pain. Pregabalin possess analgesic property and reduce neuropathy-related pain symptoms while Mecobalamin facilitates myelinogenesis and nerve regeneration. Conclusion: Fixed Dose Combination of Mecobalamin and Pregabalin has the potential analgesic effect, reduced neuropathic orofacial pain at a below than determined dosage in case of inferior alveolar and facial nerve neuropathic pain.

Combining fecal 16 S rRNA sequencing and spinal cord metabolomics analysis to explain the modulatory effect of PPARα on neuropathic pain

BackgroundExisting evidence suggests that the composition of the gut microbiota is associated with neuropathic pain (NP), but the mechanistic link is elusive. Peroxisome proliferator-activated receptor α (PPARα) has been shown to be a pharmacological target for the treatment of metabolic disorders, and its expression is also involved in inflammatory regulation. The aim of this study was to investigate the important modulatory effects of PPARα on gut microbiota and spinal cord metabolites in mice subjected to chronic constriction injury. MethodsWe analyzed fecal microbiota and spinal cord metabolic alterations in mice from the sham, CCI, GW7647 (PPARα agonist) and GW6471 (PPARα antagonist) groups by 16 S rRNA amplicon sequencing and untargeted metabolomics analysis. On this basis, the intestinal microbiota and metabolites that were significantly altered between treatment groups were analyzed in a combined multiomics analysis. We also investigated the effect of PPARα on the polarization fractionation of spinal microglia. ResultsPPARα agonist significantly reduce paw withdrawal threshold and paw withdrawal thermal latency, while PPARα antagonist significantly increase paw withdrawal threshold and paw withdrawal thermal latency. 16 S rRNA gene sequencing showed that intraperitoneal injection of GW7647 or GW6471 significantly altered the abundance, homogeneity and composition of the gut microbiome. Analysis of the spinal cord metabolome showed that the levels of spinal cord metabolites were shifted after exposure to GW7647 or GW6471. Alterations in the composition of gut microbiota were significantly associated with the abundance of various spinal cord metabolites. The abundance of Licheniformes showed a significant positive correlation with nicotinamide, benzimidazole, eicosanoids, and pyridine abundance. Immunofluorescence results showed that intraperitoneal injection of GW7647 or GW6471 altered microglial activation and polarization levels. ConclusionOur study shows that PPARα can promote M2-type microglia polarization, as well as alter gut microbiota and metabolites in CCI mice. This study enhances our understanding of the mechanism of PPARα in the treatment of neuropathic pain.

A Comprehensive Narrative Review of Neuropathic Pain: From Pathophysiology to Surgical Treatment.

Neuropathic pain is a challenging condition. Despite the immense progress made in the pathophysiology and treatment of such conditions, so much work still has to be done. New frontiers previously unexplored are now objects of study with exciting results, mainly regarding neuromodulation and optogenetics. This review explores the already known pathophysiology and the clinical and surgical treatment in the light of evidence-based medicine. Additionally, new concepts and insights are discussed, presenting the hope for the development of new paradigms in the treatment of neuropathic pain.

Pregabalin-Induced Parkinsonism: Case Report and Review of the Literature.

Pregabalin is an anti-epileptic drug approved for the treatment of neuropathic pain and focal-onset seizures. In a few cases, pregabalin was associated with parkinsonism. We present a case of a 48-year-old female who had hypertension and was on losartan 50mg/daily. Her general practitioner prescribed pregabalin 150mg/daily for fibromyalgia-related pain. The subject doubled the dosage without medical advice. After 5 days of the increased dosage, she started to experience difficulty and slowness in movement associated with resting tremors. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Secondary parkinsonism was suspected, so pregabalin was discontinued. The subject fully recovered within 7days. To the authors' knowledge, only 6 cases of pregabalin-induced parkinsonism were reported in the literature. Pregabalin discontinuation was the most common management. All individuals fully recovered after pregabalin withdrawal. The mechanism of pregabalin-induced parkinsonism is not fully understood.

Treatment of neuropathic pain by traditional Chinese medicine: An updated review on their effect and putative mechanisms of action.

Neuropathic pain (NP) is a common chronic pain with heterogeneous clinical features, and consequent lowering of quality of life. Currently, although conventional chemical drugs can effectively manage NP symptoms in the short term, their long-term efficacy is limited, and they come with significant side effects. In this regard, traditional Chinese medicine (TCM) provides a promising avenue for treating NP. Numerous pharmacological and clinical studies have substantiated the effectiveness of TCM with multiple targets and mechanisms. We aimed to outline the characteristics of TCM, including compound prescriptions, single Chinese herbs, active ingredients, and TCM physical therapy, for NP treatment and discussed their efficacy by analyzing the pathogenesis of NP. Various databases, such as PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang database, were searched. We focused on recent research progress in NP treatment by TCM. Finally, we proposed the future challenges and emerging trends in the treatment of NP. TCM demonstrates significant clinical efficacy in NP treatment, employing multi-mechanisms. Drawing from the theory of syndrome differentiation, four types of dialectical treatments for NP by compound TCM prescriptions were introduced: promoting blood circulation and removing blood stasis; promoting blood circulation and promote Qi flow; warming Yang and benefiting Qi; soothing the liver and regulating Qi. Meanwhile, 33 single Chinese herbs and 25 active ingredients were included. In addition, TCM physical therapy (e.g., acupuncture, massage, acupoint injection, and fumigation) also showed good efficacy in NP treatment. TCM, particularly through the use of compound prescriptions and acupuncture, holds bright prospects in treating NP owing to its diverse holistic effects. Nonetheless, the multi-targets of TCM may result in possible disadvantages to NP treatment, and the pharmacological mechanisms of TCM need further evaluation. Here, we provide an overview of NP treatment via TCM, based on the pathogenesis and the potential therapeutic mechanisms, thus providing a reference for further studies.

Botulinum Toxin Subdermal Injection for the Treatment of Neuropathic Pain in Ramsay Hunt Syndrome (P5-13.006)

Botulinum Toxin Subdermal Injection for the Treatment of Neuropathic Pain in Ramsay Hunt Syndrome (P5-13.006)

Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50mg/kg) and pregabalin (15mg/kg), choosing the effectual dose of 10mg/kg and the dose of 5mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50mg/kg gabapentin and 15mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.

Decrypting the multifaceted peripheral neuropathy based on molecular pathology and therapeutics: a comprehensive review.

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern. A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake. Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.