Application of SHLP2 in preparation of medicine for relieving and treating acute and chronic inflammatory pain

Abstract

The invention belongs to the technical field of medicine, and discloses application of SHLP2 in preparation of medicine for relieving and treating acute and chronic inflammatory pain, and the amino acid sequence of SHLP2 polypeptide is MGVKFFTLSTRFFPSVQRAVPLWTNS. After the SHLP2 polypeptide is treated in an intrathecal (5 [mu] g / 10 [mu] g / 20 [mu] g) injection mode, the SHLP2 polypeptide shows a good treatment effect in an acute inflammation pain model induced by formalin and capsaicin and a chronic inflammation pain model induced by carrageenan and a complete Freund's adjuvant. The SHLP2 is utilized to target a mitochondrial genome, the effect of relieving acute and chronic inflammatory pain is achieved in a central sheath injection mode, and a target different from a traditional analgesic drug can be searched for treatment of the acute and chronic inflammatory pain.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a use of SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain. Background Art

[0002] Inflammatory pain is a type of pain triggered by tissue damage or inflammation, a physiological protective response to noxious stimuli. It is characterized by the typical symptoms of inflammation (redness, swelling, heat, and pain). Following tissue damage or infection, immune cells (such as macrophages and neutrophils) release large amounts of proinflammatory cytokines and pain mediators. Sustained peripheral inflammatory signals are transmitted to the spinal cord and brain, leading to amplification of pain signals by the central nervous system, resulting in chronic pain. Currently, pharmacological treatments for inflammatory pain primarily rely on nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and other medications. Long-term use of NSAIDs, such as ibuprofen and aspirin, carries the risk of gastrointestinal and cardiovascular side effects. For example, the selective COX-2 inhibitor rofecoxib was withdrawn from the market due to cardiovascular risks. Long-term use of glucocorticoids, such as prednisone and dexamethasone, can cause side effects such as immunosuppression and osteoporosis. Therefore, they are often administered by local injection, limiting their use. Other drugs, such as acetaminophen, are not NSAIDs, but their anti-inflammatory and analgesic effects are weaker and overdose may cause hepatotoxicity. Therefore, finding new pain modulation targets is of vital importance for the development of analgesic drugs.

[0003] Here, we discovered that a polypeptide (a polypeptide encoded by mitochondrial 16S rRNA, named SHLP2) can produce significant analgesic effects in both acute and chronic inflammatory pain models. The data are detailed below.

[0004] Through the above analysis, the problems and defects of the existing technology are as follows:

[0005] Existing analgesics have poor efficacy and many and severe side effects. Summary of the Invention

[0006] In response to the problems existing in the prior art, the present invention provides a use of SHLP2 in the preparation of a drug for alleviating and treating acute and chronic inflammatory pain.

[0007] The present invention is achieved by using SHLP2 in the preparation of a drug for relieving and treating acute and chronic inflammatory pain, including:

[0008] The SHLP2 is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 1;

[0009] Among them, the polypeptide with the amino acid sequence shown in SEQ ID NO: 1 in the sequence listing consists of 26 amino acid residues.

[0010] Another object of the present invention is to provide a method for using SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain:

[0011] Step 1: The amino acid sequence of the SHLP2 polypeptide is MGVKFFTLSTRFFPSVQRAVPLWTN S. After intrathecal injection (5 μg / 10 μg / 20 μg), the SHLP2 polypeptide demonstrated significant therapeutic effects in formalin- and capsaicin-induced acute inflammatory pain models, and in carrageenan- and complete Freund's adjuvant-induced chronic inflammatory pain models.

[0012] Step 2, using SHLP2 to target the mitochondrial genome, achieves the effect of relieving acute and chronic inflammatory pain through central intrathecal injection, which can explore a target for the treatment of acute and chronic inflammatory pain that is different from traditional analgesics.

[0013] Furthermore, the pain is symptoms related to acute inflammatory pain and chronic inflammatory pain, including formalin-induced acute inflammatory pain, capsaicin-induced acute inflammatory pain, complete Freund's adjuvant-induced chronic inflammatory pain, and carrageenan-induced chronic inflammatory pain.

[0014] Another object of the present invention is to provide a product that can relieve and treat acute and chronic inflammatory pain, wherein the active ingredient is the polypeptide molecule;

[0015] The administration method of the product includes intrathecal injection, and the effective amount of SHLP2 is: central administration (intrathecal injection: 5μg / 10μg / 20μg).

[0016] In combination with the above technical solutions and the technical problems solved, the advantages and positive effects of the technical solutions to be protected by the present invention are as follows:

[0017] This invention proposes for the first time that SHLP2 can be used as a drug target for the treatment of acute and chronic inflammatory pain. Experiments have shown that intrathecal injection of SHLP2 (5 μg) relieves pain in both formalin- or capsaicin-induced acute inflammatory pain and complete Freund's adjuvant- or carrageenan-induced chronic inflammatory pain models in mice. This invention provides a drug target distinct from traditional analgesics for the treatment of acute and chronic inflammatory pain. The polypeptide SHLP2 of this invention has potential for the treatment of acute and chronic inflammatory pain.

[0018] Acute and chronic inflammatory pain creates a huge personal and economic burden and is the most common type of pain in clinical practice. Currently, the treatment of acute and chronic inflammatory pain is still mainly through drug therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are suitable for patients with mild to moderate inflammatory pain, but they are not effective in many moderate to severe patients. It is reported that a considerable proportion (nearly half) of moderate to severe patients respond poorly to these first-line drugs and cannot obtain adequate or lasting pain relief. This is the primary challenge facing clinical practice. Opioid analgesics act on opioid receptors in the central nervous system, inhibit the conduction of pain signals, and can produce a powerful analgesic effect, but the risk of abuse and addiction caused by long-term use has become a global public health crisis, limiting its widespread use in inflammatory pain. Therefore, in response to the current treatment dilemma of "effective but unsafe, safe but not effective enough", finding new treatments for acute and chronic inflammatory pain has become a major clinical need that needs to be urgently addressed.

[0019] The polypeptide SHLP2 proposed in the present invention has a good therapeutic effect in various acute and chronic inflammatory pain models. Therefore, the polypeptide SHLP2 proposed in the present invention, a new pain treatment target, is of vital importance for the development of drugs for acute and chronic inflammatory pain. Mitochondria may play a key role in the occurrence, maintenance, and chronicity of inflammatory pain. The present invention proposes for the first time that the polypeptide SHLP2 encoded by the mitochondrial genome has a good therapeutic effect in various acute and chronic inflammatory pain models. The present invention shows that SHLP2 can be used as a target for alleviating and treating acute and chronic inflammatory pain, which is of great significance for the future development of drugs and the prevention and / or treatment of such diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a flow chart of a method for using SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain, as provided in an embodiment of the present invention;

[0021] Figure 2 Schematic diagram of the therapeutic effect of intrathecal injection of SHLP2 in formalin-induced acute inflammatory pain model mice provided by an embodiment of the present invention;

[0022] Figure 3 Schematic diagram of the therapeutic effect of intrathecal injection of SHLP2 in capsaicin-induced acute inflammatory pain model mice provided by an embodiment of the present invention;

[0023] Figure 4 This is a schematic diagram of the therapeutic effect of intrathecal injection of SHLP2 in carrageenan-induced chronic inflammatory pain model mice provided by an embodiment of the present invention;

[0024] Figure 5Schematic diagram of the therapeutic effect of intrathecal injection of SHLP2 in a chronic inflammatory pain model mouse induced by complete Freund's adjuvant (CFA) provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0026] The use of SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain provided by an embodiment of the present invention includes:

[0027] SHLP2: a polypeptide having the amino acid sequence shown in SEQ ID NO: 1;

[0028] Among them, the polypeptide with the amino acid sequence shown in SEQ ID NO: 1 in the sequence listing consists of 26 amino acid residues.

[0029] like Figure 1 As shown, an embodiment of the present invention provides a method for using SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain:

[0030] S101, the amino acid sequence of the SHLP2 polypeptide is MGVKFFTLSTRFFPSVQRAVPLWTNS; after intrathecal injection (5 μg / 10 μg / 20 μg), the SHLP2 polypeptide demonstrated significant therapeutic effects in formalin- and capsaicin-induced acute inflammatory pain models, and in carrageenan- and complete Freund's adjuvant-induced chronic inflammatory pain models.

[0031] S102 utilizes SHLP2 to target the mitochondrial genome and relieves acute and chronic inflammatory pain through central intrathecal injection. It can explore a target for the treatment of acute and chronic inflammatory pain that is different from traditional analgesics.

[0032] The pain provided by the embodiments of the present invention is symptoms related to acute inflammatory pain and chronic inflammatory pain, including formalin-induced acute inflammatory pain, capsaicin-induced acute inflammatory pain, complete Freund's adjuvant-induced chronic inflammatory pain, and carrageenan-induced chronic inflammatory pain.

[0033] The embodiment of the present invention provides a product that has the effect of relieving and treating acute and chronic inflammatory pain, wherein the active ingredient is the polypeptide molecule;

[0034] The administration method of the product includes intrathecal injection, and the effective amount of SHLP2 is: central administration (intrathecal injection: 5μg / 10μg / 20μg).

[0035] The present invention is specifically implemented:

[0036] The experimental methods in the following examples and the reagents required for peptide synthesis, such as Tris, trifluoroacetic acid, deionized water, phenol, ninhydrin, chloranil, acetaldehyde, dichloromethane, N,N-dimethylformamide (DMF), anhydrous methanol, anhydrous ether, pyridine, and piperidine, were all purchased from Xilong Chemical. The amino acids required for peptide synthesis, such as 2-CTC resin (100-200 mesh, DVB 1%, S = 0.4 mmol / g), DIEA, HOBT, HBTU, HATU, HOAT, and the required amino acids were all purchased from Shanghai Jier Biochemical Co., Ltd.

[0037] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0038] The C57BL / 6 experimental mice in the following examples were healthy male mice weighing 20-25 g and were obtained from the Experimental Animal Center of Xuzhou Medical University.

[0039] Example 1: Synthesis and purification of polypeptide SHLP2

[0040] The peptide SHLP2 was synthesized in the laboratory based on the Fmoc solid-phase peptide synthesis method and then purified by high-performance liquid chromatography. The specific synthesis method is as follows:

[0041] (1) Resin treatment: First, the resin was swollen with dichloromethane (DCM), and the first amino acid and condensing agents HOBT and HBTU were added. The mixture was stirred for 5 min, and DIEA was added. After the reaction for 1 h, methanol was added to terminate the reaction. After 30 min, the resin was washed with DMF, and then washed alternately with methanol and DCM. The resin was dried and the substitution value was measured.

[0042] (2) Extension of the peptide chain on the resin: Place the resin with the first amino acid back into the peptide synthesizer and, according to the peptide amino acid sequence, condense the fully protected amino acids one by one from the C-terminus to the N-terminus of the peptide according to step (1). After each step is completed, the residual reagents need to be filtered out by negative pressure. Repeat step (2) until the extension of the C-terminal amino acid to the N-terminus of the peptide sequence is completed, and then drain the resin.

[0043] (3) Peptide cleavage: the cleavage agent is thioanisole: phenol: TFA: EDT: deionized water = 5:5:85:2.5:2.5, ether precipitation, freeze-drying, and HPLC preparation.

[0044] (4) Peptide purification: The crude peptide synthesized above was purified by column chromatography. Approximately 50 mg of the crude product was weighed and dissolved in 1 ml of 20% acetonitrile. The product was filtered through a plastic filter tip and then purified by column chromatography using an acetonitrile / water / 0.1% trifluoroacetic acid system at a flow rate of 8 ml / min for 60 minutes. The main peak was collected and lyophilized. The lyophilized sample was then subjected to mass spectrometry analysis.

[0045] Example 2: Application of SHLP2 in formalin-induced acute inflammatory pain

[0046] (1) Construction of formalin-induced acute inflammatory pain model: This experiment used 22±2g male C57BL / 6 mice, kept in a quiet room at 22±1℃. The mice were numbered and placed in an observation box to adapt for 15 minutes. Different concentrations of the test analogue were given. Five minutes later, 20μL of 5% formalin solution was injected subcutaneously (sc) into the right hind paw of the mouse using a microsyringe. The mouse was immediately returned to the observation box, and the cumulative time of licking, biting, and shaking the hind paw was recorded in 0-5 minutes (phase 1) and 15-30 minutes (phase 2). 0.9% saline was used as a negative control. The experimental results are expressed as the cumulative time of licking, biting, and shaking the hind paw.

[0047] (2) The results showed that in mice with acute inflammatory pain induced by formalin, intrathecal injection of SHLP2 (5 μg / 10 μg / 20 μg) could significantly alleviate the acute inflammatory pain caused by formalin (P < 0.05) (see Figure 2 ).

[0048] Example 3: Application of SHLP2 in capsaicin-induced acute inflammatory pain

[0049] (1) Construction of capsaicin-induced acute inflammatory pain model: This experiment used 22±2g male C57BL / 6 mice, kept in a quiet room at 22±1℃. The mice were numbered and placed in an observation box to adapt for 15 minutes. Different concentrations of the test analogue were given. Five minutes later, 20μL of 1% capsaicin solution was injected subcutaneously (sc) into the right hind paw of the mouse using a microsyringe, which successfully induced an acute inflammatory pain model. The total time and total number of licking and biting of the mouse's paw within 0-15 minutes were recorded, and behavioral changes such as mechanical pain threshold at 30 minutes and 60 minutes were recorded to reflect the role of SHLP2 in acute inflammatory pain.

[0050] (2) The results show that: Figure 3 SHLP2 was injected intrathecally (5μg / 10μg / 20μg). SHLP2 had a significant analgesic effect 30min and 60min after capsaicin injection, indicating that SHLP2 has a therapeutic effect on capsaicin-induced acute inflammatory pain.

[0051] Example 4: Application of SHLP2 in carrageenan-induced chronic inflammatory pain

[0052] (1) Construction of carrageenan-induced chronic inflammatory pain model: Carrageenan is a sulfate-containing polysaccharide extracted from seaweed and has been widely used in the construction of chronic inflammatory pain models. This experiment used 22±2g male C57BL / 6 mice, kept quiet in the room, and the room temperature was 22±1℃. 0.1ml of 0.5% carrageenan (carrageenan type I, Sigma, prepared with physiological saline) was injected subcutaneously into the sole of the hind limb of the mouse. After a few minutes, the local swelling rapidly occurred, and the animal showed spontaneous pain behaviors such as repeated lifting and licking of the foot. After about 24h, the spontaneous pain behavior disappeared, forming a chronic inflammatory pain model, which can be used for drug screening. Within 24h-7d, the mice were numbered and placed in an observation box to adapt for 15min. Different concentrations of the test analogs were given, and the behavioral changes such as thermal pain and mechanical pain threshold of the mice were recorded every 20 minutes to reflect the role of SHLP2 in chronic inflammatory pain.

[0053] (2) The results show that: Figure 4 Mice showed significant pain hypersensitivity within 7 days after carrageenan injection. Intrathecal injection of SHLP2 (5μg / 10μg / 20μg) demonstrated a significant analgesic effect within 2 hours of administration, as measured by behavioral tests such as Von Frey mechanical allodynia and thermal radiation allodynia. These data suggest that SHLP2 has therapeutic effects on carrageenan-induced chronic inflammatory pain.

[0054] Example 5: Application of SHLP2 in chronic inflammatory pain induced by complete Freund's adjuvant

[0055] (1) Construction of a chronic inflammatory pain model induced by complete Freund's adjuvant: This experiment used male C57BL / 6 mice weighing 22±2g. The room was kept quiet and the room temperature was 22±1℃. 25μL of complete Freund's adjuvant (CFA) solution was drawn with a microinjector. The needle was inserted into the toe of the mouse's hind paw on one side and the CFA solution was slowly injected into the subcutaneous area of ​​the mouse's palm to form a skin bump. The needle was stopped for 20 seconds and then slowly rotated out to avoid liquid leakage. About 1 to 14 days after CFA injection, a chronic inflammatory pain model can be formed for drug screening. Within 1-14 days, the mice were numbered and placed in an observation box to adapt for 15 minutes. Different concentrations of the test analogs were given, and behavioral changes such as thermal pain and mechanical pain threshold of the mice were recorded every 20 minutes to reflect the role of SHLP2 in chronic inflammatory pain.

[0056] (2) The results show that: Figure 5Mice showed significant pain hypersensitivity within 1-14 days after CFA injection. Intrathecal injection of SHLP2 (5μg / 10μg / 20μg) demonstrated a significant analgesic effect within 2 hours of administration, as measured by behavioral tests such as Von Frey mechanical allodynia and thermal radiation allodynia. These data suggest that SHLP2 has therapeutic effects on CFA-induced chronic inflammatory pain.

[0057] Example 6: Study on behavioral detection scheme of mechanical pain and thermal pain

[0058] The SHLP2 provided in the embodiments of the present invention is a polypeptide composed of 26 amino acids encoded by the mitochondrial 16S rRNA genome, and the sequence is:

[0059] SHLP2(MGVKFFTLSTRFFPSVQRAVPLWTNS).

[0060] In the early stages of this study, SHLP2 was found to have an effective analgesic effect in a formalin / capsaicin / carrageenan / CFA-induced acute and chronic inflammatory pain model through intrathecal injection. Therefore, the present invention predicts that SHLP2 is involved in the regulation of acute and chronic inflammatory pain and could serve as a drug target for the treatment of acute and chronic inflammatory pain.

[0061] In the embodiments of the present invention, SHLP2 can be administered centrally (intrathecal injection: 5 / 10 / 20 μg) to relieve pain in both acute and chronic inflammatory pain models induced by formalin / capsaicin / carrageenan / CFA in mice.

[0062] The behavioral detection method provided in the embodiments of the present invention for verifying the use of SHLP2 in the preparation of a drug for relieving and / or treating pain includes:

[0063] (1) Mechanical pain threshold test of mice: Use VonFrey fibers to calculate the paw withdrawal threshold using the up-down method. Gently place the mouse in the test cage and allow it to move freely. Wait until it is quiet (usually takes 30-45 minutes), with its limbs standing naturally on the grid and no obvious exploratory behavior (such as sniffing, climbing, and grooming) before starting the test. According to preliminary experiments or literature, select a medium-intensity vonFrey fiber (such as the 0.04g starting fiber commonly used in mice). If a negative reaction occurs, give a stimulus of the next higher intensity; if a positive reaction occurs, use a stimulus of the next lower intensity until the first positive and negative reactions occur. Then measure four times in a row, with the upper limit of the maximum intensity being 4.31 (2g), and the interval between each stimulus being 30s. Mainly stimulate the middle area of ​​the plantar of the hind limb (avoid the foot pad). Make sure the stimulation point is located in the center of the plantar, close to the metatarsal area. Slowly extend the tip of the wire upward through the mesh holes, gently contacting the target plantar skin. Apply continuous, steady pressure until the wire bends into a "C" shape (reaching its calibration force value) and maintains this bend for approximately 2-4 seconds. The movements should be gentle, steady, and consistent. Avoid rapid prodding, dragging, or multiple proddings. The paw withdrawal threshold (PWT) is often calculated using the Dixon nonparametric method or the Chaplan formula.

[0064] (2) Hargreaves thermal radiation pain threshold test for mice: The mice were placed on the glass plate of the test box and acclimatized for 30-45 minutes (ambient temperature 23-25°C). After acclimatization for 30 minutes, the light beam was irradiated to the middle part of the sole of the hind limb (avoiding the foot pad) with a fixed intensity (40W). The equipment automatically recorded the latency from irradiation to paw withdrawal (accurate to 0.01 second). This was repeated three times with an interval of at least 5 minutes each time, and the average value was taken. The upper limit of the thermal radiation time was set to 20 seconds to prevent burns on the sole of the mouse's foot.

[0065] (3) Data statistics: All experimental data were statistically analyzed using SPSS 19.0 (mean ± SEM). Multiple group comparisons were performed using one-way ANOVA. P < 0.05 was considered statistically significant. The statistical method for time- and dose-dependent data was based on the Bonferroni-test method of multivariate ANOVA. P < 0.05 indicated a significant difference.

[0066] The above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions and improvements made by any technician familiar with this technical field within the technical scope disclosed by the present invention and within the spirit and principles of the present invention should be covered by the scope of protection of the present invention.

[0067] Relevant evidence of the technical effects achieved by the embodiments of the present invention.

[0068] <110> Li Weiwei

[0069] <120> Use of SHLP2 in preparing drugs for relieving and treating acute and chronic inflammatory pain

[0070] <160> 1

[0071] <210> 1

[0072] <211> 16

[0073] <212> PRT

[0074] <213> Artificial Sequence MGVKFFTLSTRFFPSVQRAVPLWTNS

[0075] <400> 1

[0076] Example 1: Formalin acute inflammatory pain model (Materials and methods)

[0077] Twenty-four healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into a control group, a model group, a low-dose SHLP2 group (1 μg), and a high-dose SHLP2 group (5 μg), with six rats in each group. An intrathecal catheter was placed 24 hours before the experiment, and only rats with good postoperative recovery were included in the study. Thirty minutes before injection, 10 μL of SHLP2 solution (prepared with sterile saline) was administered intrathecally into the tail. Equal volumes of saline were injected intrathecally into the control and model groups. Subsequently, 50 μL of 2% formalin solution was injected subcutaneously into the right hind paw to establish an acute inflammatory pain model. Real-time video recording was used to record the duration and frequency of paw licking and lifting over a period of 0–60 minutes.

[0078] Compared with the model group, both low- and high-dose SHLP2 groups significantly reduced spontaneous pain behaviors in rats during both the first (0–10 minutes) and second (10–60 minutes) formalin infusion phases. In the high-dose group, total paw licking time decreased by approximately 48% and the average number of paw lifts decreased by 42% during the second phase (P < 0.01). Regardless of dose, there were no significant differences in the animals' walking ability, body weight, or degree of local redness and swelling, demonstrating that SHLP2 has a potent immediate analgesic effect without significant toxic side effects. This suggests that intrathecal administration of SHLP2 can significantly alleviate acute inflammatory pain.

[0079] Example 2: Complete Freund's Adjuvant (CFA) Chronic Inflammatory Pain Model (Materials and Methods)

[0080] Thirty healthy male C57BL / 6 mice weighing 22±2g were randomly divided into a control group, a model group, a low-dose SHLP2 group (0.5μg / d-1), a medium-dose group (1μg / d-1), and a high-dose group (2μg / d-1), with six mice in each group. Chronic inflammatory pain was induced by subcutaneous injection of 20μL of CFA suspension into the plantar surface of the right hind paw. Daily intrathecal injections were administered starting on the day of modeling and continued for 7 consecutive days. Mechanical withdrawal thresholds (MPTs) were measured using Von Frey fibers and thermal withdrawal latencies (TPLTs) were measured using a Hargreaves apparatus before drug administration (D0) and on D1, D3, D5, and D7. Spinal cord samples from L4–L6 were harvested on D7 to measure IL-1β and TNF-α mRNA expression.

[0081] Mechanical thresholds and thermal latencies significantly decreased in the model group starting on Day 1 (P < 0.01). However, thresholds gradually recovered starting on Day 3 in the medium- and high-dose SHLP2 groups. By Day 7, mechanical thresholds increased by 58% and 76%, respectively, and thermal latencies prolonged by 44% and 61% (both P < 0.01). qPCR results showed that spinal cord IL-1β and TNF-α transcript levels decreased by approximately 37% and 49%, respectively, in the medium- and high-dose groups compared with the model group, suggesting effective suppression of inflammatory factors. No motor abnormalities or weight loss were observed throughout the treatment period, indicating that SHLP2 also has sustained, dose-dependent analgesic and anti-inflammatory effects on chronic inflammatory pain, providing a viable approach for the development of novel mitochondrial-targeted analgesics.

[0082] The above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions and improvements made by any technician familiar with this technical field within the technical scope disclosed by the present invention and within the spirit and principles of the present invention should be covered by the scope of protection of the present invention.

Claims

1. A use of SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain, characterized in that: The SHLP2 is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 1; Among them, the polypeptide with the amino acid sequence shown in SEQ ID NO: 1 in the sequence listing consists of 26 amino acid residues.

2. A method for using SHLP2 as claimed in claim 1 in preparing a drug for relieving and treating acute and chronic inflammatory pain, characterized in that: The use of SHLP2 in preparing drugs for relieving and treating acute and chronic inflammatory pain: Step 1: The amino acid sequence of the SHLP2 polypeptide is MGVKFFTLSTRFFPSVQRAVPLWTN S. After intrathecal injection, the SHLP2 polypeptide exhibited a good therapeutic effect in both formalin- and capsaicin-induced acute inflammatory pain models and carrageenan- and complete Freund's adjuvant-induced chronic inflammatory pain models. Step 2, using SHLP2 to target the mitochondrial genome, achieves the effect of relieving acute and chronic inflammatory pain through central intrathecal injection, which can explore a target for the treatment of acute and chronic inflammatory pain that is different from traditional analgesics.

3. The use of SHLP2 in preparing a drug for relieving and treating acute and chronic inflammatory pain according to claim 1, characterized in that: The pain is symptoms related to acute inflammatory pain and chronic inflammatory pain, including formalin-induced acute inflammatory pain, capsaicin-induced acute inflammatory pain, complete Freund's adjuvant-induced chronic inflammatory pain, and carrageenan-induced chronic inflammatory pain.

4. A product having the effect of relieving and treating acute and chronic inflammatory pain, comprising the use of SHLP2 as claimed in claim 1 in the preparation of a drug for relieving and treating acute and chronic inflammatory pain, wherein the active ingredient is the polypeptide molecule; The administration method of the product includes intrathecal injection, and the effective amount of SHLP2 is: central administration.

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