Herb-drug interactions: A short review on central and peripheral nervous system drugs.

Herbal medicines are widely perceived as natural and safe remedies. However, their concomitant use with prescribed drugs is a common practice, often undertaken without full awareness of the potential risks and frequently without medical supervision. This practice introduces a tangible risk of herb-drug interactions, which can manifest as a spectrum of consequences, ranging from acute, self-limited reactions to unpredictable and potentially lethal scenarios. This review offers a comprehensive overview of herb-drug interactions, with a specific focus on medications targeting the Central and Peripheral Nervous Systems. Our work draws upon a broad range of evidence, encompassing preclinical data, animal studies, and clinical case reports. We delve into the intricate pharmacodynamics and pharmacokinetics underpinning each interaction, elucidating the mechanisms through which these interactions occur. One pressing issue that emerges from this analysis is the need for updated guidelines and sustained pharmacovigilance efforts. The topic of herb-drug interactions often escapes the attention of both consumers and healthcare professionals. To ensure patient safety and informed decision-making, it is imperative that we address this knowledge gap and establish a framework for continued monitoring and education. In conclusion, the use of herbal remedies alongside conventional medications is a practice replete with potential hazards. This review not only underscores the real and significant risks associated with herb-drug interactions but also underscores the necessity for greater awareness, research, and vigilant oversight in this often-overlooked domain of healthcare.

Food-induced stimulation of the antisecretory factor to improve symptoms in Meniere's disease: our results.

PURPOSE: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone. METHODS: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered. RESULTS: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group. CONCLUSION: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

The role of nonmuscle myosin II in polydrug memories and memory reconsolidation.

Using pharmacologic and genetic approaches targeting actin or the actin-driving molecular motor, nonmuscle myosin II (NMII), we previously discovered an immediate, retrieval-independent, and long-lasting disruption of methamphetamine- (METH-) and amphetamine-associated memories. A single intrabasolateral amygdala complex infusion or systemic administration of the NMII inhibitor Blebbistatin (Blebb) is sufficient to produce this disruption, which is selective, having no retrieval-independent effect on memories for fear, food reward, cocaine, or morphine. However, it was unclear if Blebb treatment would disrupt memories of other stimulants and amphetamine class drugs, such as nicotine (NIC) or mephedrone (MEPH; bath salts). Moreover, many individuals abuse multiple drugs, but it was unknown if Blebb could disrupt polydrug memories, or if the inclusion of another substance would render Blebb no longer able to disrupt METH-associated memories. Therefore, the present study had two primary goals: (1) to determine the ability of Blebb to disrupt NIC- or MEPH-associated memories, and (2) to determine the ability of METH to modify other unconditioned stimulus (US) associations' susceptibility to Blebb. To this end, using the conditional place preference model, mice were conditioned to NIC and MEPH alone or METH in combination with NIC, morphine, or foot shock. We report that, unlike METH, there was no retrieval-independent effect of Blebb on NIC- or MEPH-associated memories. However, similar to cocaine, reconsolidation of the memory for both drugs was disrupted. Further, when combined with METH administration, NIC- and morphine-, but not fear-, associated memories were rendered susceptible to disruption by Blebb. Given the high rate of polydrug use and the resurgence of METH use, these results have important implications for the treatment of substance use disorder.

Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats.

Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/µm, and the tension was significantly decreased to ∼29 pN/µm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/µm by methyl-ß-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions.

Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation.

Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.

Amyotrophic Lateral Sclerosis Incidence and Previous Prescriptions of Drugs for the Nervous System.

BACKGROUND: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. METHODS: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014. Exposure to nervous system drugs was measured until 2012, or until 1 year before ALS onset. The association was estimated for ever and cumulative exposure, through Cox proportional Hazards models adjusted for sex, age, education, marital status and drug co-exposure. RESULTS: In the analysis for ever exposure, opioids were significantly inversely associated with ALS risk (hazard ratio (HR) 0.59; 95% CI 0.35-0.97), while antiepileptics (HR 1.35; 95% CI 0.92-2.00) showed a marginally significantly positive association. Examining cumulative exposure, the protective role of opioids associated with more than 4 prescriptions and the risk effect of antiepileptics for over 6 prescriptions was confirmed. CONCLUSIONS: The present study revealed associations of ALS onset with previous exposure to opioids, maybe through the activation of δ receptor and σ receptors and antiepileptics, which are novel findings to our knowledge.

The use of botulinum toxin in the treatment of sialorrhea in parkinsonian disorders.

Drooling is a common symptom in parkinsonian disorders. Our aim was to assess the safety and effect of botulinum toxin when applied to parotid glands without ultrasound guidance for sialorrhea in parkinsonian disorders in a retrospective study with a long-term follow-up. We evaluated 53 patients (64.2% male and 35.8% female) with a mean age of 70.18 ± 9.25 years who were treated in our centre between 2007 and 2013. We analysed the mean dose, latency, effect duration, response and adverse effects of treating sialorrhea by injecting botulinum toxin type A (Botox) into the parotid glands without ultrasound guidance. A total of 41 patients with Parkinson's disease, 6 with progressive supranuclear palsy, 4 with multiple system atrophy and 2 with corticobasal degeneration were included. The mean duration of the disease at onset was 10.51 ± 6.81 years and the mean sialorrhea duration was 1.99 ± 1.55 years. The initial dose used for each parotid gland was 14.53 ± 3.95 units of Botox, with a mean dose of 22.17 ± 8.76 units. There was an improvement after treatment in 65.22% of patients with an average score of 6.85 ± 1.58 points on a scale from 0 to 10. The duration of the treatment effect was 4.38 ± 2.11 months, with a latency period of 10.06 ± 9.63 days. Adverse effects were mild and infrequent. Botulinum toxin is a safe and effective therapy for the treatment of sialorrhea in parkinsonian disorders and there is no requirement for ultrasound guidance. It has a rapid onset and lasting effect without requiring a high dosage.

C3 toxin and poly-DL-lactide-ε-caprolactone conduits in the critically damaged peripheral nervous system: a combined therapeutic approach.

INTRODUCTION: Peripheral nerve regeneration over longer distances through conduits is limited. In the presented study, critical size nerve gap bridging with a poly-DL-lactide-ε-caprolactone (PLC) conduit was combined with application of C3 toxin to facilitate axonal sprouting. MATERIALS AND METHODS: The PLC filled with fibrin (n = 10) and fibrin gel loaded with 1-µg C3-C2I and 2-µg C2II (n = 10) were compared to autologous nerve grafts (n = 10) in a 15-mm sciatic nerve gap lesion model of the rat. Functional and electrophysiological analyses were performed before histological evaluation. RESULTS: Evaluation of motor function and nerve conduction velocity at 16 weeks revealed no differences between the groups. All histological parameters and muscle weight were significantly elevated in nerve graft group. No differences were observed in both PLC groups. CONCLUSIONS: The PLCs are permissive for nerve regeneration over a 15-mm defect in rats. Intraluminal application of C3 toxin did not lead to significant enhancement of nerve sprouting.

Responses of intact and injured sural nerve fibers to cooling and menthol.

Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6-12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact (n = 12) and 90% of injured (n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers (n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers (n = 25) and almost no A-fibers (n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.

In-stream attenuation of neuro-active pharmaceuticals and their metabolites.

In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

Remyelination in humans due to a retinoid-X receptor agonist is age-dependent.

Remyelination efficiency declines with advancing age in animal models, but this has been harder to demonstrate in people with multiple sclerosis. We show that bexarotene, a putatively remyelinating retinoid-X receptor agonist, shortened the visual evoked potential latency in patients with chronic optic neuropathy aged under 42 years only (with the effect diminishing by 0.45 ms per year of age); and increased the magnetization transfer ratio of deep gray matter lesions in those under 43 years only. Addressing this age-related decline in human remyelination capacity will be an important step in the development of remyelinating therapies that work across the lifespan.

On benzofuroindole analogues as smooth muscle relaxants.

At least two laboratories have independently reported the synthesis of benzofuroindole compounds having potential therapeutic implications in many disease states including those that involve smooth muscle hyperactivity. Through a series of in vitro screenings, they demonstrated the efficacy (and selectivity) of these compounds to potentiate large conductance calcium- (Ca²âº-) activated K⁺ (BK(Ca)) channels, by far, the most characterized of all Ca²âº-dependent K⁺ channels. Interestingly, promising benzofuroindole derivatives such as compound 7 (10H-benzo[4,5]furo[3,2-b]indole) and compound 22 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) both exhibited high bladder (versus aorta) selectivity, making them attractive alternative treatments for bladder overactivity. In recent reports, compound 22 (LDD175 or TBIC) also showed inhibition of ileum and uterine contractions, indicating multiple target tissues, which is not surprising as BK(Ca) channels are ubiquitously expressed in the animal and human tissues. In this paper, the authors discuss the value of benzofuroindole compounds and the challenges that need to be overcome if they were considered as smooth muscle relaxants.

The time to develop treatments for diabetic neuropathy.

BACKGROUND: Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). METHODS: We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search terms included small fiber neuropathy,diffuse peripheral neuropathy, quantitative sensory testing, nerve conduction testing, intra-epidermal nerve fiber density, corneal confocal reflectance microscopy, aldose reductase inhbitors, nerve growth factor, alpha-lipoic acid, ruboxistaurin, nerve growth factor antibody, and cibinetide. RESULTS: Over the past half century, there have been a number of agents undergoing unsuccessful trials for treatment of DPN.There are several approved agents for relief of pain caused by diabetic neuropathy, but these do not affect the pathologic process. EXPERT OPINION: The failure to find treatments for diabetic neuropathy can be ascribed to (1) the complexity of design of studies and (2) the slow progression of the condition, necessitating long duration trials to prove efficacy.We propose a modification of the regulatory process to permit early introduction of agents with demonstrated safety and suggestion of benefit as well as prolongation of marketing exclusivity while long term trials are in progress to prove efficacy.

Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulation.

BACKGROUND: Peptidergic neurons store and secrete the contents of large dense core vesicles (LDCVs) from axon terminals and from dendrites. Secretion of peptides requires a highly regulated exocytotic mechanism, plus coordinated synthesis and transport of LDCVs to their sites of release. Although these trafficking events are critical to function, little is known regarding the dynamic behavior of LDCVs and the mechanisms by which their transport is regulated. Sensory neurons also package opiate receptors in peptide-containing LDCVs, which is thought to be important in pain sensation. Since peptide granules cannot be refilled locally after their contents are secreted, it is particularly important to understand how neurons support regulated release of peptides. RESULTS: A vector encoding soluble peptidylglycine alpha-hydroxylating monooxygenase fused to green fluorescent protein was constructed to address these questions in cultured primary peptidergic neurons of the trigeminal ganglion using time lapse confocal microscopy. The time course of release differs with secretagogue; the secretory response to depolarization with K+ is rapid and terminates within 15 minutes, while phorbol ester stimulation of secretion is maintained over a longer period. The data demonstrate fundamental differences between LDCV dynamics in axons and growth cones under basal conditions. CONCLUSIONS: Under basal conditions, LDCVs move faster away from the soma than toward the soma, but fewer LDCVs travel anterograde than retrograde. Stimulation decreased average anterograde velocity and increases granule pausing. Data from antibody uptake, quantification of enzyme secretion and appearance of pHluorin fluorescence demonstrate distributed release of peptides all along the axon, not just at terminals.

Thickened saliva after effective management of drooling with botulinum toxin A.

AIM: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. METHOD: We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ<70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT-A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT-A treatment. RESULTS: Both submandibular salivary flow rate (baseline 0.38 mL/min; 24 wks after injection 0.26 mL/min) and drooling quotient (baseline 42.5%; 24 wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830 U/mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. INTERPRETATION: When making decisions about the use of BoNT-A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT-A treatment should be taken into account.

Recurrent vasovagal syncope: comparison between clomipramine and nitroglycerin as drug challenges during head-up tilt testing.

AIMS: To compare the responses between clomipramine, a centrally acting substance, and nitroglycerin, with mainly peripheral action, when each drug is used during tilt test for the induction of vasovagal syncope (VVS). METHODS AND RESULTS: Hundred patients with recurrent episodes of classical VVS underwent two tilt tests in a randomized sequence. One test included 20 min of tilt at 60 degrees with intravenous administration of 5 mg clomipramine (clomipramine tilt), whereas the other test included an initial 30 min period of passive 60 degrees tilt, followed by sublingual spray administration of 400 microg nitroglycerin (nitroglycerin tilt). Fifty asymptomatic subjects served as controls. Following clomipramine tilt, a positive response occurred in 73 patients (73%), a negative response in 23 (23%), and drug intolerance in 4 (4%). With nitroglycerin tilt, these percentages were 52, 48, and 0%, respectively. Significant differences were observed regarding positive responses (clomipramine vs. nitroglycerin: 73/100 vs. 52/100, P < 0.05), as well as negative responses (23/100 vs. 48/100, respectively, P < 0.05). A high concordance rate was observed in positive responses. CONCLUSION: In the evaluation of patients with recurrent classical VVS, clomipramine tilt is associated with an increased positive yield relative to nitroglycerin tilt. This suggests that central mechanisms may be more important than peripheral ones in VVS pathogenesis.

[Pharmacological treatment of diabetic neuropathy in the elderly]. / Tratamiento farmacológico de la neuropatía diabética dolorosa en el anciano.

Diabetic neuropathy is the third most common complication of diabetes mellitus. When this neuropathy is accompanied by pain, it requires a specific treatment. In the elderly patient, the pain has an enormous impact on quality of life, as it is associated with anxiety, depression and sleep disorders, leading to a direct impact on the functionality of the patient. Likewise, there are a number of changes at the central and peripheral nervous system, which contribute to the chronicity of painful processes, and eventually also affect and impact on the quality of life of elderly patients. It is fundamental before initiating treatment, to know of all aspects related to drug pharmacokinetics and pharmacodynamics, especially those related to aging, because this will allow you to select the best drug for each patient. This article aims to review the pathophysiological concepts related to diabetic neuropathy in the elderly and the best treatment options.

Modeling drug exposure in rodents using e-cigarettes and other electronic nicotine delivery systems.

Smoking tobacco products is the leading cause of preventable death worldwide. Coordinated efforts have successfully reduced tobacco cigarette smoking in the United States; however, electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) recently have replaced traditional cigarettes for many users. While the clinical risks associated with long-term ENDS use remain unclear, advancements in preclinical rodent models will enhance our understanding of their overall health effects. This review examines the peripheral and central effects of ENDS-mediated exposure to nicotine and other drugs of abuse in rodents and evaluates current techniques for implementing ENDS in preclinical research.

Calcitonin gene-related peptide antagonists versus botulinum toxin A for the preventive treatment of chronic migraine protocol of a systematic review and network meta-analysis: A protocol for systematic review.

BACKGROUND: Although calcitonin gene-related peptide antagonists and botulinum toxin A have been shown efficacy in preventing chronic migraine, there is no direct evidence for their comparative effectiveness. This review is to assess the comparative effectiveness and safety of calcitonin gene-related peptide antagonists and botulinum toxin A for chronic migraine using network meta-analysis. METHODS: OVID MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials will be searched for relevant randomized controlled trials from their inception to December 2019 without language restriction. We will include trials testing the effectiveness of calcitonin gene-related peptide antagonists or botulinum toxin A in patients with chronic migraine. The outcomes are mean change from baseline in the number of headache days, the mean change from baseline in the number of migraine days, the mean change from baseline in headache hours, responder rate, and adverse events rate. The methodological quality of the included randomized controlled trials will be evaluated using Cochrane Collaboration's risk of bias tool. Standardized mean difference will be used to synthesize continuous variables and risk ratio will be used to synthesize categorical variables. Pairwise and network meta-analysis will be performed using a frequentist method in netmeta package (R 3.5.0, www.r-project.org). RESULTS: Ethical approval and informed consent are not required for this systematic review. The results will be submitted to a peer-reviewed journal and conference abstracts for publication. CONCLUSION: The result of the review will systematically provide suggestions for clinicians, patients, and policy makers in the treatment of chronic migraine.PROSPERO registration number: CRD42018089201.

Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System.

Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridiumbotulinum, the causing agent for botulism, in different serotypes, seven of which (A-G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking SNARE (soluble N-ethylmale-imide-sensitive factor-attachment protein receptors) complex formation and vesicle release from the neuronal terminal through the specific cleavage of SNARE proteins. The action of BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field has set the foundation for the use of these toxins in a variety of human pathologies characterized by excessive muscle contractions. In parallel, BoNTs became a cosmetic drug due to its power to ward off facial wrinkles following the activity of the mimic muscles. Successively, BoNTs became therapeutic agents that have proven to be successful in the treatment of different neurological disorders, with new indications emerging or being approved each year. In particular, BoNT/A became the treatment of excellence not only for muscle hyperactivity conditions, such as dystonia and spasticity, but also to reduce pain in a series of painful states, such as neuropathic pain, lumbar and myofascial pain, and to treat various dysfunctions of the urinary bladder. This review summarizes recent experimental findings on the potential efficacy of BoNTs in favoring nerve regeneration after traumatic injury in the peripheral nervous system, such as the injury of peripheral nerves, like sciatic nerve, and in the central nervous system, such as spinal cord injury.