CN114306359B - Analgesic uses of Pulsatilla or its extracts - Google Patents

Abstract

The invention provides an application of pulsatilla saponin B5 or a pharmaceutically acceptable salt, eutectic, stereoisomer, prodrug, solvate and metabolite thereof in preparing a medicament for preventing and/or treating pain, which can significantly relieve the severity of neuropathic pain, for example, improve the mechanical pain threshold caused by von Frey nylon filament vertical stimulation or the cold pain threshold caused by acetone stimulation of a spinal nerve ligation model, and has more excellent effect compared with the conventional pregabalin, and can alleviate the economic burden of neuropathic pain patients and society, improve the life quality of patients, and has higher economic value, and the popularization and application are suggested.

Description

Analgesic uses of Pulsatilla or its extracts

technical field

The invention relates to the technical field of biomedicine, in particular to the application of Pulsatilla saponin B5 in the preparation of analgesic medicines.

Background technique

Neuropathic pain has become the top killer of chronic pain due to its long course, poor efficacy, and serious impact on the quality of life of patients. Due to its high incidence and complex pathogenesis, there is still no effective treatment for the disease. Currently, drug treatment is the mainstay of treatment. Commonly used first-line analgesic drugs include tricyclic antidepressants (TCA), serotonin-nor Adrenaline reuptake inhibitors (SNRIs) and gabapentin, etc. The main effect of these drugs is not analgesia, but they are later found to have analgesic effects, so they are listed as adjuvant analgesics. Liver dysfunction, arrhythmia, mental illness and elderly patients have various side effects, such as dry mouth, sweating, excessive sleep and gastrointestinal reactions. Effective drugs make the therapeutic effect better, without significant side effects, and achieve a better therapeutic effect.

In the research on the treatment of neuropathic pain, there are many traditional Chinese medicines based on their analgesic efficacy, such as the publication number CN112494505A, the name is the use of echinacoside in the preparation of drugs for the treatment of neuropathic pain; another example is the publication number CN107137413A, the name is The application of Pulsatilla saponin B4 in the preparation of medicine for treating pain, it was found that Pulsatilla saponin B4 has good effects on acetic acid-induced mouse writhing model, thermal radiation pain model, formalin-induced mouse pain model and rat pain model of pain relief. However, the structures of Pulsatilla saponin B4 and Pulsatilla saponin B5 are quite different, and the parent nucleus of the aglycone is different. The former is a lupinane-type saponin, and the latter is an oleanane-type saponin, and the patent adopts the classic neuropathic pain ( spinal nerve ligation) model, and revealed the analgesic molecular mechanism of Pulsatilla saponin B5 by transcriptome sequencing.

Pulsatilla saponin B5 is one of the main active components of traditional Chinese medicine Pulsatilla, belonging to saponins. Modern pharmacological studies have shown that it has pharmacological effects such as anti-inflammatory, antiviral, antitumor, antioxidative, antihistamine and enhancing human immunity. The vast majority of researches reported before are carried out around the many activities of Pulsatilla saponin B4, and there are few studies on the activity of Pulsatilla saponin B5 at present. The application in the drug of infection has proved that it has strong antiviral activity, but there is no report on the analgesia of Pulsatilla saponin B5.

SUMMARY OF THE INVENTION

The present invention provides a new use of Pulsatilla saponin B5, namely preventing and/or treating pain. And through the examples, it has been confirmed that Pulsatilla saponin B5 can significantly alleviate the severity of neuropathic pain, such as increasing the mechanical pain threshold caused by vertical stimulation of vonFrey nylon fibers in the spinal nerve ligation model or the cold pain threshold caused by acetone stimulation, etc. Pregabalin is more effective. The analgesic mechanism of Pulsatilla saponin B5 is related to the inhibition of chemokine signaling and other neural pathways, and can be used to prepare a therapeutic drug for neuropathic pain. And while the pain was effectively relieved, the rats were in good condition and no significant side effects were found.

The first aspect of the present invention provides the application of Pulsatilla or its extract in preparing a medicine for preventing and/or treating pain.

Described Pulsatilla is Pulsatilla or its dry root.

The Pulsatilla extract includes Pulsatilla saponins, preferably oleanane-type saponins.

In a specific embodiment of the present invention, the pulsatilla extract includes pulsatilla saponin B5, and its structural formula is as follows:

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The pain includes neuropathic pain. Neuropathic pain (NP) is a chronic pain characterized by clinical symptoms such as burning pain, stabbing pain, and tearing pain, and can also trigger negative emotions such as depression and anxiety in patients. It is defined by the International Association for the Study of Pain as "pain stimulated or caused by primary injury and dysfunction of the nervous system".

Preferably, the neuropathic pain includes peripheral sensitization, central sensitization and/or central descending inhibitory regulation changes, etc., and specific common inducements are chemotherapy, spinal cord injury, mitochondrial dysfunction and/or diabetes and other diseases. Peripherally sensitized neuropathic pain is preferred.

In a specific embodiment of the present invention, the pain includes mechanical pain or cold pain.

Preferably, said preventing and/or treating pain comprises increasing pain threshold.

Preferably, said preventing and/or treating pain comprises administering to the individual an effective amount of Pulsatilla or its extract.

Preferably, the medicine includes Pulsatilla or its extract, and pharmaceutically acceptable excipients.

The second aspect of the present invention provides oleanane-type saponins or their pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates and metabolites in the preparation of drugs for preventing and/or treating pain applications in .

Said preventing and/or treating pain comprises administering to the individual an effective amount of oleanane-type saponin or a pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof.

The medicament includes oleanane-type saponins or pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates, metabolites, and pharmaceutically acceptable excipients.

The third aspect of the present invention provides the application of Pulsatilla saponin B5 or its pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates and metabolites in the preparation of medicines for preventing and/or treating pain .

The pain includes neuropathic pain.

The pain includes mechanical pain or cold pain.

Said preventing and/or treating pain includes increasing pain threshold.

Said preventing and/or treating pain comprises administering to the individual an effective amount of Pulsatilla saponin B5 or a pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof.

The medicament includes Pulsatilla saponin B5 or its pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates, metabolites, and pharmaceutically acceptable excipients.

Preferably, the medicine further comprises other Pulsatilla extracts except Pulsatilla saponin B5.

Described Pulsatilla saponin B5 can be obtained by artificial synthesis or extraction from Pulsatilla.

The fourth aspect of the present invention provides the application of Pulsatilla or its extract in regulating genes or their encoded proteins, the genes or their encoded proteins include Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, One or a combination of two or more of Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b, or Guca1a .

The fifth aspect of the present invention provides oleanane-type saponins or their pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates, metabolites, or, Pulsatilla saponins B5 or their pharmaceutically acceptable salts. Use of acceptable salts, co-crystals, stereoisomers, prodrugs, solvates, and metabolites in regulating genes or their encoded proteins, including Slc24a1, Gch1, RT1-A2, Cd74 , Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b, or Guca1a or a combination of two or more.

The sixth aspect of the present invention provides the use of a gene or its encoded protein as a target for preventing and/or treating pain, the gene or its encoded protein including Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1 , one or both of Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b or Guca1a and combination of the above.

The seventh aspect of the present invention provides the application of a reagent regulating gene or its encoded protein in the preparation of a medicine for preventing and/or treating pain, said gene or its encoded protein including Slc24a1, Gch1, RT1-A2, Cd74, One of Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b or Guca1a or A combination of two or more.

Preferably, the prevention and/or treatment of pain includes regulating the expression level of a gene or the concentration of its encoded protein.

Preferably, the regulation includes up-regulation or down-regulation. Wherein, the up-regulation can be overexpressing the corresponding gene or increasing the concentration of the corresponding protein. Down-regulation can be knocking out or knocking down the corresponding gene or adding an inhibitor of the corresponding protein. Further, the agent for regulating the gene or its encoded protein can be adapted to the required agent according to the method of up-regulating or down-regulating the gene or its encoded protein.

The agent for regulating the gene or its encoded protein comprises Pulsatilla or its extract.

The agent for regulating gene or its encoded protein comprises alanane saponin or its pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite, or, Pulsatilla saponin B5 or its pharmacy Acceptable salts, co-crystals, stereoisomers, prodrugs, solvates, metabolites of the above.

The medicines include reagents for regulating genes or their encoded proteins, and pharmaceutically acceptable excipients.

The eighth aspect of the present invention provides a method for preventing and/or treating pain, the method comprising applying an effective amount of Pulsatilla or its extract to an individual, or applying an effective amount of oleanane to an individual Saponin or its pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite, or, Pulsatilla saponin B5 or its pharmaceutically acceptable salt, co-crystal, stereoisomer, pro- Drugs, solvates, metabolites.

The ninth aspect of the present invention provides a method for preventing and/or treating pain, the method comprising regulating a gene or its encoded protein.

The Pulsatilla described in the present invention includes, but is not limited to, Chinese Pulsatilla, Korean Pulsatilla, Korean Pulsatilla, Elongatus Pulsatilla or Pulsatilla genus, that is, plants belonging to the genus Ranunculus (Ranunculus family).

The "Pulstula vulgaris extract" of the present invention includes, but is not limited to, ranunculus, deoxypodophyllotoxin and 3-oxo-α-L-rhamnopyranosyl (1→2)-[β-D-glucopyranose (1→4)]-α-L-arabinopyranoside and the like. It can be extracted by methods conventional in the art, such as alcohol extraction.

"Prevention" as used in the present invention refers to a method implemented in order to prevent or delay the occurrence of a disease, disorder or symptom in the body.

"Treatment" as used herein means slowing, interrupting, arresting, controlling, stopping, alleviating, or reversing the progression or severity of a sign, symptom, disorder, condition, or disease after the disease has begun to develop, but not necessarily Involves complete elimination of all disease-related signs, symptoms, conditions, or disorders.

An "effective amount" as used herein refers to the amount or dose of the medicament of the present invention that provides the desired treatment or prevention following administration to an individual or organ in single or multiple doses.

The "individual" in the present invention can be a human or a non-human mammal, and the non-human mammal can be a wild animal, a zoo animal, an economic animal, a pet, an experimental animal and the like. Preferably, the non-human mammals include but are not limited to pigs, cattle, sheep, horses, donkeys, foxes, raccoons, minks, camels, dogs, cats, rabbits, mice (such as rats, mice, guinea pigs, hamsters) , gerbil, chinchilla, squirrel) or monkey, etc.

"Pharmaceutically acceptable" as used herein means neither significantly stimulating the organism nor inhibiting the biological activity and properties of the active substance of the administered product.

The "pharmaceutically acceptable salts" in the present invention refer to salts prepared from pharmaceutically acceptable non-toxic acids or bases, wherein the acids or bases include inorganic acids or bases or organic acids or bases. The inorganic acid is selected from hydrochloric acid, hydrobromic acid, phosphoric acid, hydroiodic acid or sulfuric acid. The inorganic base is selected from calcium, magnesium, lithium, sodium, zinc, aluminum or potassium. Described organic acid is selected from formic acid, glycolic acid, propionic acid, acetic acid, succinic acid, methanesulfonic acid, ethanesulfonic acid, maleic acid, glutamic acid, benzoic acid, stearic acid, alginic acid, benzenesulfonic acid acid, glucuronic acid, pamoic acid or galacturonic acid. The organic base is selected from diethanolamine, choline, procaine, lysine or 1,2-ethylenediamine.

The "co-crystal" in the present invention refers to the compounds of the present invention (such as oleanane-type saponin or Pulsatilla saponin B5) and other physiologically acceptable acids, bases, non-ionic compounds, through hydrogen bonding, van der Waals force, A crystal formed by the combination of non-covalent bonds such as π-π stacking and halogen bonds.

The "stereoisomers" in the present invention include enantiomers, diastereomers and geometric isomers.

The "prodrug" in the present invention refers to a drug that is inactive or less active in vitro or at a non-specific target site after chemical structure modification, and releases the active drug through enzymatic or non-enzymatic transformation in vivo (for example, the compound of the present invention). Alanane-type saponin or Pulsatilla saponin B5) and a compound that exerts medicinal effects.

"Solvate" as used herein refers to the physical association of a compound of the present invention (eg, oleanane-type saponin or Pulsatilla saponin B5) with one or more solvent molecules. This physical bond includes various degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate may be isolated, for example when one or more solvent molecules are incorporated into the crystal lattice of the crystalline solid. Solvates include solution phases and isolatable solvates. Representative solvates include ethanolates, methanolates, and the like.

The "metabolites" in the present invention refer to the products obtained by chemically degrading the compounds of the present invention (eg, oleanane-type saponins or Pulsatilla saponins B5) under physiological conditions in vivo.

The "pharmaceutically acceptable adjuvants" in the present invention include but are not limited to carriers, excipients, diluents, wetting agents, fillers, binders, lubricants, disintegrants, antioxidants, buffers , one or more of suspending agents, solubilizers, thickeners, stabilizers, flavoring agents and preservatives.

The medicaments of the present invention can be administered by any suitable route of administration, such as gastrointestinal (eg, oral) or parenteral (eg, intravenous, intramuscular, subcutaneous, intradermal, intraorgan, nasal intraocular, instillation, intracerebral, intrathecal, transdermal, intrarectal, etc.) routes. In a specific embodiment of the present invention, the route of administration is oral or injection.

The medicament of the present invention can be in any suitable dosage form, such as a gastrointestinal or parenteral dosage form, preferably including but not limited to tablets, pills, powders, granules, capsules, lozenges doses, syrups, liquids, emulsions, microemulsions, suspensions, injections, sprays, aerosols, powders, lotions, ointments, plasters, pastes, patches, eye drops, nasal drops tablets, sublingual tablets, suppositories, aerosols, effervescent tablets, drop pills, gels, etc.

The single application dose of the medicament of the present invention is limited to the dose that does not cause central depression.

Various dosage forms of the medicament of the present invention can be prepared according to the conventional production methods in the pharmaceutical field.

The medicine of the present invention may contain 0.01-99.5% by weight (specifically, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8% %, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%) of the compound (eg olean Alkane saponin or Pulsatilla saponin B5) or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate or metabolite thereof.

The medicine of the present invention can be human medicine or veterinary medicine.

In the present invention, "comprising" or "comprising" is an open-ended description containing the specified elements or steps described, as well as other specified elements or steps that are not substantially affected.

In the present invention, "and/or" includes all combinations of the items to which the term is linked, and it should be construed that each combination has been individually listed in this question. For example, "A and/or B" includes "A", "A and B", and "B". As another example, "A, B and/or C" includes "A", "B", "C", "A and B", "A and C", "B and C", and "A and B and C" ".

Description of drawings

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, wherein:

Figure 1: 50% paw withdrawal threshold detection results of rats in each group after administration.

Figure 2: The comparison results of the number of reaction times of cold pain or licking of the rats in each group after administration to acetone stimulation.

Figure 3A: Analysis results of differentially expressed genes between SNL and Con groups.

Figure 3B: Analysis results of differentially expressed genes between SNL and B5 groups.

Figure 4A: Differentially expressed genes were subjected to KEGG enrichment analysis, and the main signaling pathways regulated by the differentially expressed genes in the SNL group and the Con group were obtained.

Figure 4B: Differentially expressed genes were subjected to KEGG enrichment analysis, and the main signaling pathways regulated by the differentially expressed genes in the SNL and B5 groups were obtained.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

Experimental animals used in the examples: SD rats, male, 210-230 g, SPF grade, purchased from Speifu (Beijing) Biotechnology Co., Ltd., license number: SCXK (Beijing) 2019-0010. Animals were housed in the animal room of the Institute of Chinese Medicine, Chinese Academy of Chinese Medical Sciences.

The spinal nerve ligation (Spinal Nerve Liation, SNL) model used in the examples is recognized as an ideal neuropathic pain model, simulating the disease state of neuropathic pain (Neuropatic Pain, NP), and investigating the analgesic effect of Pulsatilla saponin B5 to relieve NP Features.

The pregabalin capsules used in the examples were purchased from Pfizer Pharmaceuticals Co., Ltd., approved by Chinese medicine J20100102.

Example 1

1. Experimental method

1. Construction of SNL rat model

After the rats were anesthetized, the back skin was exposed by shaving. Cut the skin perpendicular to the line connecting the spine and the anterior superior iliac spine. The tissue was dissected by microscopy and the transverse process of the left L6 vertebral body was found, exposing the L4 and L5 spinal nerves. The L4 and L5 spinal nerves were separated and the L5 spinal nerve was ligated with surgical suture.

2. Experimental drugs and reagents

2% Sodium Pentobarbital; Pulsatilla Saponin B5; Pregabalin Capsules.

3. Animal grouping and administration

Negative control group (Con), model group (SNL), Pulsatilla saponin B5 group (B5 for short), and pregabalin group (PGB).

There were 10 rats in each group. After modeling, the rats recovered for 3 days, and then were continuously administered for 14 days. Among them, B5 was intraperitoneally injected (dose of 4.15 mg/kg), and PGB was administered by gavage (dose of 22.5 mg/kg). kg), and rats in the Con and SNL groups were given an equal volume of normal saline by gavage.

Tissue sampling: After the administration period, the rats were anesthetized and the hippocampal tissue of the brain was removed. After washing with PBS, it was stored in a cryovial at -80°C for transcriptome sequencing.

4. Detection method of mechanical pain

The mechanical pain threshold in the L5 reflex area of the left foot of rats was detected by von Frey nylon fibers (stimulation force in the detection range of 0.008g-300g). The rats were placed in individually closed cages in a quiet environment. The skin of the left palmar surface of the rat was stimulated vertically with von Frey nylon filaments. The stimulation intensity was adjusted by replacing the von Frey nylon filaments. Until the filaments are bent, the rat's paw withdrawal response is positive within 5 seconds. The 50% paw withdrawal response threshold was calculated according to the up-and-down method. The 50% paw withdrawal threshold detection time points were set at 1h, 1.5h, 2h, 3h, 5h, and 7h after the last administration.

5. Cold pain threshold detection method

Cold pain threshold was detected using acetone stimulation. The rats were placed in separate closed cages to keep the environment quiet. The rats were given 20uL of acetone on the left dorsum of the foot to stimulate the rats to withdraw or lick their feet. The number of foot withdrawal or foot licking reflexes within 30s was recorded. The cold pain threshold detection time point was set at 2h after the end of the last administration.

6. Screening of differentially expressed genes

According to the transcriptome data, we generally use the log2 (fold change) method to screen for differentially expressed genes, and use the R heatmap package to perform hierarchical clustering analysis.

7. Pathway enrichment analysis

The screened differentially expressed genes were analyzed by GO database for cellular component (CC), molecular function (MF), biological process (BP) and pathway analysis using KEGG database. The related pathways of B5 exerting analgesic effect were obtained through enrichment analysis.

2. Experimental results

1. B5 significantly increased the mechanical pain threshold of SNL rats

The results are shown in Figure 1. At the end of administration (1h, 1.5h, 2h, 3h, 5h), the mechanical pain threshold in the SNL group was significantly lower than that in the Con group ( P < 0.05). Compared with the administration group, the B5 group and the pregabalin group could increase the mechanical pain threshold of the SNL rats to different degrees. After 2 h of administration, the B5 group had the most significant effect on increasing the mechanical pain threshold of SNL rats ( P < 0.05), and was significantly better than the pregabalin group ( P < 0.05).

2. B5 increased the cold pain threshold in SNL rats

The results are shown in Figure 2. On the 2nd hour after administration, the cold pain threshold of the SNL group was significantly lower than that of the Con group, that is, the number of animals' foot withdrawal or licking response to cold pain caused by acetone stimulation increased ( P < 0.01). Compared with the administration group, the B5 group and the pregabalin group in the SNL group both increased the cold pain threshold of the SNL rats, that is, significantly reduced the number of the animals' foot withdrawal or licking response to cold pain caused by acetone stimulation. The increase in cold pain threshold was most significant in mice ( P < 0.05).

3. Differentially expressed genes

Differentially expressed genes were analyzed between SNL and Con groups, and 323 differentially expressed genes were obtained. There were 49 up-regulated genes and 274 down-regulated genes (see Figure 3A). There were 829 differentially expressed genes in SNL and B5 groups, including 692 up-regulated genes and 137 down-regulated genes (see Figure 3B).

4. Pathway enrichment analysis

KEGG enrichment analysis was performed according to the differentially expressed genes, and the signal pathways mainly regulated by the differentially expressed genes between the SNL group and the Con group (see Figure 4A) and between the SNL and B5 groups (see Figure 4B) were obtained. Among them, the common signal pathways enriched by SNL group, Con group and B5 group include Phototransduction (phototransduction), Nitrogen metabolism (nitrogen metabolism), Graft-versus-host disease (graft-versus-host disease), and Folate biosynthesis (folic acid biosynthesis). ), Allograft rejection, Autoimmune thyroid disease, Type I diabetes mellitus, Viral myocarditis, Cocaine addiction, Antigen processing and presentation (antigen processing and presentation), Complement and coagulation cascades (complement pathway), Dilatedcardiomyopathy (dilated cardiomyopathy). These shared signaling pathways contain the same 25 differentially expressed genes (Slc24a1 gene, Gch1 gene, RT1-A2 gene, Cd74 gene, Car13 gene, Grk1 gene, Rgs9 gene, Car3 gene, C7 gene, Cacna1f gene, Tph1 gene, A2m gene Gene, Gnat2 gene, Ddc gene, LOC100911545 gene, Lama2 gene, Cngb1 gene, RT1-Ba gene, Cacna2d4 gene, Pde6g gene, RT1-Da gene, Adrb1 gene, Gngt1 gene, Guca1b gene, Guca1a gene). It is suggested that Pulsatilla saponin B5 may play a role in relieving neuropathic pain by regulating the above 25 genes.

The preferred embodiments of the present invention are described in detail above, but the present invention is not limited to the specific details of the above-mentioned embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention. These simple modifications All belong to the protection scope of the present invention.

In addition, it should be noted that the specific technical features described in the above-mentioned specific embodiments can be combined in any suitable manner unless they are inconsistent. In order to avoid unnecessary repetition, the present invention provides The combination method will not be specified otherwise.

Claims (4)

1. The application of the pulsatilla saponin B5 or the pharmaceutically acceptable salt thereof in preparing the medicine for preventing and/or treating neuropathic pain is characterized in that the neuropathic pain is psychroalgia.

2. The use according to claim 1, wherein said prevention and/or treatment of neuropathic pain comprises an increase in cold pain threshold.

3. The use according to claim 1, wherein the prevention and/or treatment of neuropathic pain comprises administering an effective amount of pasqueflower saponin B5 or a pharmaceutically acceptable salt thereof to an individual.

4. The use according to any one of claims 1 to 3, wherein the medicament comprises pulsatilla saponin B5 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

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