Rodent arthralgia threshold measuring device and method

By designing a rodent joint pain threshold measurement device and combining it with a pressure sensor and a camera, a simple, fast and continuous pain threshold measurement is achieved, which solves the problems of difficult operation and inaccurate results in the existing technology and improves measurement efficiency and accuracy.

CN120616453APending Publication Date: 2025-09-12SICHUAN UNIV
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Patent Information

Application Number
CN202510962029.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-07-11
Publication Date
2025-09-12

AI Technical Summary

Technical Problem

Existing devices and methods for measuring rodent joint pain thresholds have problems such as difficult operation, discontinuity and inaccurate results, which make it difficult to meet the needs of simple, fast and continuous measurement of pain thresholds.

Method used

A rodent joint pain threshold measurement device was designed, which includes a shell, a pressure sensor, an automatic telescopic device and a camera. The pain threshold is automatically determined by continuously collecting pressure signals and behavioral images, combining the time-pressure change curve and animal behavior information.

Benefits of technology

The method realizes simple, rapid and continuous measurement of rodent joint pain threshold, improves measurement efficiency and accuracy, and reduces manual operation errors.

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Abstract

The invention discloses a rodent arthralgia threshold value measuring device and method, and relates to the field of pain sense measurement, the rodent arthralgia threshold value measuring device is characterized in that a pressure sensor is movably connected to a shell, and an automatic telescopic device is arranged in the shell; a pressure sensing probe is arranged on the pressure sensor; the automatic telescopic device is connected with the pressure sensor; the pressure sensor is connected with the display screen through a signal converter in the shell; a camera is arranged on the shell; the camera is connected with the display screen through a signal converter; the display screen is used for displaying a time-pressure change curve and animal behavior information; and based on the time-pressure change curve and the animal behavior information, taking the pressure value of the pressure sensing probe corresponding to the time point when the rodent has the effective withdrawal behavior as the pain threshold of the rodent joint, so that the requirement of simply, conveniently, quickly and continuously measuring the pain threshold is met, and the efficiency of measuring the pain threshold of the joint is improved.
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Description

Technical Field

[0001] The present application relates to the field of pain measurement, and in particular to a device and method for measuring the joint pain threshold of rodents. Background Art

[0002] According to the International Association for the Study of Pain (IASP), pain is “an unpleasant sensory and emotional experience associated with, or described in terms of, actual or potential tissue damage.” The purpose of pain is to alert the individual to withdraw from the immediate tissue-damaging stimulus and to prevent further damage to the injured area during the healing process.

[0003] Currently, the global prevalence of arthritis is substantial and continues to grow. The age of onset is significantly younger, the disease burden is growing, and the risk factors are becoming increasingly complex, making it a significant factor affecting people's quality of life. In daily life, joint pain serves as a core signal for the body's self-protection, alerting us to potential injury and limiting excessive activity. Research on human joint pain behavior can provide a deeper understanding of the pathogenesis of joint pain, thereby providing a scientific basis for the development of more effective treatments, improving patients' quality of life, and alleviating the inconvenience and psychological burden caused by pain.

[0004] Because research on human pain behavior is difficult and ethically restricted, rodents are often used to study the pathophysiological mechanisms of pain. Therefore, pain threshold measurement is a research direction for the treatment of arthritis. The pain threshold refers to the minimum stimulus intensity that causes pain. That is, when the stimulus intensity exceeds this critical value, the body will produce a pain response.

[0005] Because pain perception in rodents cannot be directly measured, numerous methods have been developed to quantify "pain-like" behaviors or nociception. These behavioral methods can be categorized as stimulus-evoked or non-stimulus-evoked (spontaneous) nociception, depending on whether an external stimulus is used to induce a withdrawal response. Methods for measuring mechanical pain thresholds primarily include manual and electronic von Frey tests and the Randall-Selitto test. Specifically, the Randall-Selitto test applies increasing mechanical forces to the surface of the paw or tail until the rat flinches or vocalizes. In practice, this test is very effective for assessing the pain threshold of rats, but it is not applicable to mice because they find it difficult to tolerate strict physical constraints. In the manual and electronic von Frey tests, experimenters assess mechanical hyperalgesia by applying monofilaments of varying forces. The manual von Frey test is currently the gold standard for measuring the mechanical pain threshold of mice, but due to the discrete force application, continuous measurement data cannot be obtained. At the same time, this method is difficult to operate and takes a long time, which can easily lead to "false positive" symptoms for inexperienced experimenters. In contrast, the electronic von Frey test can obtain continuous measurement data by continuously applying force and the experimental time is greatly reduced. However, the results obtained using manual and electronic von Frey fiber tests are very different, and it is not clear whether the two methods activate different sensory neurons.

[0006] In summary, currently used pain threshold measurement devices and methods all have certain limitations and cannot meet the needs of simple, rapid, and continuous pain threshold measurement. Therefore, there is currently a lack of a simple and effective device that can continuously measure the pain threshold of rodent joints. Summary of the Invention

[0007] The purpose of this application is to provide a device and method for measuring the joint pain threshold of rodents to meet the needs of simple, fast and continuous measurement of pain threshold.

[0008] To achieve the above objectives, this application provides the following solutions:

[0009] In a first aspect, the present application provides a rodent joint pain threshold measurement device, comprising: a housing;

[0010] A pressure sensor is movably connected to the housing, and an automatic telescopic device is provided inside the housing; a pressure sensing probe is provided on the pressure sensor; the pressure sensing probe is used to apply pressure to the rodent's joint; the automatic telescopic device is connected to the pressure sensor and is used to adjust the telescopic length of the pressure sensor and the pressure sensing probe;

[0011] The pressure sensor is connected to the display screen via a signal converter in the housing, and is used to upload the pressure signal continuously collected by the pressure sensing probe to the display screen;

[0012] The housing is provided with a camera; the camera is connected to the display screen via the signal converter, and is used to capture behavioral images of rodents, capture animal behavior information in real time, and upload it to the display screen;

[0013] The display screen is used to display a time-pressure change curve and animal behavior information; based on the time-pressure change curve and the animal behavior information, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

[0014] In a second aspect, the present application provides a method for measuring the joint pain threshold of rodents, comprising:

[0015] Based on the above-mentioned rodent joint pain threshold measurement device, continuously collected pressure signals and rodent behavioral images;

[0016] Drawing a time-pressure change curve according to the pressure signal;

[0017] capturing animal behavior information in real time based on the behavior image;

[0018] determining, based on the animal behavior information, a time point at which the rodent exhibits effective withdrawal behavior;

[0019] Based on the time-pressure change curve, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

[0020] According to the specific embodiments provided in this application, this application has the following technical effects:

[0021] This application combines continuously collected pressure signals and behavioral images to draw a time-pressure change curve. On the basis of the time-pressure change curve, combined with the animal behavior information collected in real time by the behavioral image, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint. This application can continuously measure pressure signals and behavioral images, meet the needs of simple, fast and continuous measurement of pain thresholds, and improve the efficiency of joint pain threshold measurement. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0023] Figure 1 A schematic structural diagram of a rodent joint pain threshold measurement device provided in one embodiment of the present application;

[0024] Figure 2 A schematic diagram of the structure of a rodent joint pain threshold measurement device during actual operation provided by one embodiment of the present application;

[0025] Figure 3 A schematic structural diagram of an automatic telescopic device provided in one embodiment of the present application;

[0026] Figure 4 A schematic flow chart of a method for measuring joint pain threshold in rodents provided in one embodiment of the present application;

[0027] Figure 5 A schematic flow chart of a method for measuring joint pain threshold in rodents provided in another embodiment of the present application;

[0028] Figure 6 This is the timing diagram of the experimental process. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0030] In order to make the purpose, features and advantages of this application more obvious and easy to understand, this application is further described in detail below with reference to the accompanying drawings and specific implementation methods.

[0031] like Figure 1-Figure 2 As shown, an embodiment of the present application provides a rodent joint pain threshold measurement device, including: a shell 1; the measurement device is a handheld measurement device.

[0032] A pressure sensor 2 is movably connected to the shell 1, and an automatic telescopic device is provided inside the shell 1; a pressure sensing probe 3 is provided on the pressure sensor 2; the pressure sensing probe 3 is used to apply pressure to the rodent's joints; the automatic telescopic device is connected to the pressure sensor 2 and is used to adjust the telescopic length of the pressure sensor 2 and the pressure sensing probe.

[0033] In practical applications, the adjustment process involved in this application specifically includes: adjustment of the probe extension length, adjustment of the pressure growth rate, and setting of the safety threshold.

[0034] 1. Adjustment of the probe telescopic length:

[0035] (1) Manual coarse adjustment: Move the probe close to the joint position using the knob or touch interface.

[0036] (2) Automatic calibration: Click the "Zero Calibration" button, slowly bring the probe into contact with the joint surface, and pressure sensor 2 automatically returns to zero. The system records the probe's telescopic length at this point as the reference position.

[0037] (3) Stroke limit setting: Enter the maximum allowable extension length to prevent excessive stress on the joint.

[0038] 2. Regulation of pressure growth rate:

[0039] (1) Input target rate: Set the pressure increase rate on the human-machine interface.

[0040] (2)PID parameter configuration:

[0041] Default parameters: proportional coefficient (Kp=0.5), integral time (Ti=0.2s), differential time (Td=0.05s).

[0042] If optimization is required, the "adaptive parameter adjustment" function can be used to allow the system to dynamically adjust parameters based on the cylinder response.

[0043] (3) Real-time monitoring: The interface displays the pressure-time curve and verifies the linearity error (needed to be <±2%).

[0044] 3. Security threshold setting:

[0045] (1) Enter the maximum allowable pressure.

[0046] (2) Set an over-limit response strategy (such as automatically retracting the probe and triggering an alarm when the pressure exceeds the threshold).

[0047] The pressure sensor 2 is connected to the display screen 10 via the signal converter 4 in the housing 1 , and is used to upload the pressure signal continuously collected by the pressure sensing probe 3 to the display screen 10 .

[0048] The housing 1 is provided with a camera 5 ; the camera 5 is connected to the display screen 10 via the signal converter 4 , and is used to capture behavioral images of rodents, capture animal behavior information in real time, and upload the information to the display screen 10 .

[0049] The display screen 10 is used to display a time-pressure change curve and animal behavior information; based on the time-pressure change curve and the animal behavior information, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

[0050] In addition, a power supply 11 is provided in the housing 1 for supplying power to various components in the housing 1 .

[0051] In an exemplary embodiment, Figure 3 As shown, the automatic telescopic device specifically includes: a telescopic cylinder 6, a pneumatic regulating valve 7 and a compressed gas box 8 connected through a standardized interface.

[0052] The telescopic cylinder 6 is connected to the pressure sensor 2 and is used to drive the pressure sensor 2 to extend and retract, so as to adjust the telescopic length of the pressure sensing probe 3 .

[0053] The pneumatic regulating valve 7 is provided with a telescopic control button 9, which is connected to the telescopic cylinder 613 through two air pipes. The pneumatic regulating valve 7 is used to adjust the amount of gas entering the telescopic cylinder 6 to adjust the air pressure in the telescopic cylinder 6.

[0054] The pneumatic regulating valve 7 also includes structures such as an air pipe and a telescopic regulating device 7-3. The compressed gas box 8 is connected to the air inlet of the pneumatic regulating valve 7 through the air pipe to provide it with high-pressure gas as an air source power; the telescopic cylinder 6 is connected to the air outlet of the pneumatic regulating valve 7 through two air pipes, one of which is the air inlet pipe 7-1 (controls the gas entering the cylinder to push the piston to extend), and the other is the exhaust pipe 7-2 (releases the gas in the cylinder to retract the piston), thereby controlling the telescopic speed and stroke of the telescopic cylinder 6 by adjusting the gas flow; the telescopic control button 9 is connected to and controls the telescopic regulating device 7-3 to control the amount of gas entering the telescopic cylinder 6 and the air pressure in the telescopic cylinder 6.

[0055] The compressed gas tank 8 is used to store compressed gas.

[0056] The present application also includes a compressor box 12 connected to the compressed gas box 8, and the compressor box 12 is provided with a motor 12-1 and a compressor 12-2. The motor 12-1 provides energy for the operation of the compressor 12-2, and the compressor 12-2 provides gas to the telescopic cylinder 6 through the pneumatic regulating valve 7.

[0057] In actual applications, regarding the automatic telescopic device: a precision telescopic cylinder 6 structure is used for telescopic adjustment, and the cylinder body, pneumatic control valve 7, compressed gas box 8 and other components are seamlessly connected between modules through standardized interfaces. The telescopic stroke is precisely controlled through air pressure control, and the pressure increase is accurately controlled.

[0058] In practical applications, precise control of telescopic stroke through air pressure control specifically includes:

[0059] 1. Target travel setting:

[0060] The user inputs the target telescopic stroke (L_target) through the human-machine interface, and the system calculates the required air pressure (P_target) based on the cylinder diameter and piston area.

[0061] 2. Initial position calibration:

[0062] Start the "zero point calibration" function, touch the probe lightly to the joint surface, the displacement sensor records the initial position, and the pressure sensor 2 returns to zero.

[0063] 3. Air pressure closed loop control:

[0064] (1)PID algorithm execution:

[0065] Proportional (P) control: adjusts the valve opening according to the current error (e(t) = L_target - L_actual).

[0066] Integral (I) control: accumulates the error (∫e(t)dt) to eliminate steady-state deviation.

[0067] Derivative (D) control: predicts the error change trend (de(t) / dt) and suppresses overshoot oscillation.

[0068] (2) Valve adjustment: The controller outputs PWM signals to drive the proportional valve, adjust the gas flow, and control the cylinder filling / exhaust speed.

[0069] 4. Real-time feedback and dynamic compensation:

[0070] (1) The displacement sensor feeds back the piston position (L_actual) at a frequency of 1 kHz, and the pressure sensor 2 monitors the pressure in the cylinder (P_actual).

[0071] (2) Dynamic compensation strategy:

[0072] Gas compressibility compensation: Based on the ideal gas law (PV=nRT), the pressure-displacement hysteresis effect is predicted.

[0073] Friction compensation: Static / dynamic friction is estimated using the Stribeck model and added to the PID output.

[0074] 5. Reaching the target position and maintaining:

[0075] When |L_actual-L_target|≤0.01mm, enter the position holding mode:

[0076] Switch to the fine-tuning valve to fine-tune the air pressure in a pulse manner (ΔP = ±0.001 MPa).

[0077] The displacement sensor continuously monitors to prevent drift caused by gas source fluctuations or temperature changes.

[0078] 6. Security and fault tolerance mechanism:

[0079] Overpressure protection: When P_actual is greater than the safety threshold, the solenoid valve is urgently exhausted and the probe automatically retracts.

[0080] Out-of-step detection: If the displacement and pressure signals are inconsistent (such as piston sticking), a fault alarm is triggered and the machine is shut down.

[0081] Redundant design: Dual pressure sensors cross-validate to avoid single point failure.

[0082] In an exemplary embodiment, an incremental PID algorithm is used to adjust the air pressure in the telescopic cylinder 6 .

[0083] In practical applications, the pressure closed-loop control uses an incremental PID algorithm to adjust the cylinder pressure to achieve linear pressure growth:

[0084] ① Input: Target pressure growth rate (0.1 g / s). The target pressure growth rate is usually set manually by the experimenter according to experimental requirements or standardized protocols.

[0085] ② Step 1: Proportional (P): Current pressure error (e(t) = Ptarget - Pactual). Ptarget (target pressure) refers to the desired pressure value preset in the control system; Pactual (actual pressure) refers to the actual pressure value currently output by the system as measured in real time by pressure sensor 2.

[0086] 2. Integration (I): Accumulates the error (∫e(t)dt) to eliminate steady-state deviations.

[0087] 3. Differential (D): Error change rate (de(t) / dt), suppresses oscillation.

[0088] ③Output: Adjust the opening of the pneumatic valve and control the extension and retraction speed of the cylinder.

[0089] In practical applications, the three links of incremental PID control, namely proportional (P), integral (I), and differential (D), work together to adjust the opening of the pneumatic valve to ensure that the actual pressure strictly follows the target pressure growth curve. The specific links are as follows:

[0090] Proportional term (P): directly responds to the current pressure error (e(t) = P target -P actual ), quickly correct deviations.

[0091] Integral term (I): accumulates historical errors (∫e(t)dt) to eliminate long-term steady-state deviations (such as residual errors caused by gas source pressure fluctuations or frictional resistance).

[0092] Differential term (D): predicts the error change trend (de(t) / dt), suppresses overshoot and oscillation, and improves system stability.

[0093] The three work together: P provides instant response, I eliminates cumulative errors, and D suppresses fluctuations. Ultimately, the pneumatic valve opening is dynamically adjusted through weighted summation and output control signals.

[0094] Specific steps for adjusting the opening of the pneumatic valve according to the target pressure growth rate.

[0095] 1. Generation of target pressure curve:

[0096] Input target growth rate: The system generates a continuously increasing target pressure P according to time t target (t) = growth rate × t.

[0097] 2. Real-time data collection and error calculation:

[0098] Measure actual pressure P actual : The current pressure value is collected in real time through pressure sensor 2.

[0099] Calculation error e(t): e(t) = P target (t)-P actual (t)

[0100] 3. Incremental PID control quantity calculation:

[0101] Proportional term (P): P term =K p ×e(t).

[0102] Integral term (I): (Δt is the sampling period), where e(k) is the error value of the kth sampling period, that is, the difference between the target value and the actual value, that is, the aforementioned e(t) = P target (t)-P actual (t), which represents the cumulative sum of errors from the initial moment (k=0) to the current moment (k=t).

[0103] Differential term (D): D term =K d ×[e(t)-e(t-1)] / Δt.

[0104] Control increment Δu(t): Δu(t) = P term +I term +D term .

[0105] 4. Adjust the opening of the pneumatic valve:

[0106] (1) Pneumatic valve control signal mapping:

[0107] The control increment Δu(t) is converted into a pneumatic valve opening instruction (eg, 0-100% opening corresponds to a 0-10V analog signal).

[0108] (2) Real-time execution: The control signal is sent to the pneumatic valve through the proportional valve or servo valve drive circuit.

[0109] The air pressure in the cylinder changes accordingly, pushing the probe to expand and contract, thereby increasing the pressure.

[0110] 5. Closed-loop feedback and dynamic adjustment:

[0111] Real-time monitoring: continuous collection of P actual , update the error and recalculate the control quantity.

[0112] Adaptive adjustment: If the actual pressure deviates from the target curve (such as due to animal struggle or air source fluctuation), the PID parameters (K p ,K i ,K d ) can be adjusted dynamically.

[0113] Safety protection: When the pressure exceeds the safety threshold, the valve is forced to close and the probe is retracted.

[0114] In an exemplary embodiment, the camera 5 is a binocular stereo vision camera; the frame rate of the binocular stereo vision camera is 200fps.

[0115] In practical applications, Camera 5 uses a 200fps binocular stereo camera. Simulating the parallax principle of the human eye, two cameras capture images from different angles. An algorithm calculates the disparity map and generates depth information. Hardware acceleration and algorithm optimization achieve high frame rates, significantly improving tracking and positioning accuracy in dynamic scenes and capturing animal behavior in real time.

[0116] Animal behavior information specifically includes:

[0117] 1. Key body movement behaviors:

[0118] (1) Dynamic changes in joint angles:

[0119] Target joints: hip, knee, ankle, etc.

[0120] Quantitative indicators: changes in flexion / extension angle.

[0121] Capture method: Use the OpenPose algorithm to mark the coordinates of joint points in real time and calculate the angle change rate.

[0122] (2) Limb displacement trajectory:

[0123] Definition: A finding of a shift in the overall position of the stimulated limb.

[0124] Judgment condition: The displacement exceeds 10% of the initial contact position.

[0125] 3D tracking: Use binocular parallax to generate depth information and calculate the movement trajectory of limbs in 3D space.

[0126] 2. Pain-related specific behaviors:

[0127] (1) Withdrawal behavior:

[0128] Trigger condition: Pressure drop: The pressure drops by more than 20% within 5ms.

[0129] Rapid limb retraction: The joint angle change and displacement amount synchronously meet the threshold.

[0130] Judgment logic: Joint analysis of pressure signals and visual data must meet the above conditions simultaneously to avoid misjudgment.

[0131] (2) Spontaneous protective actions:

[0132] Licking behavior: The animal licks the stimulated joint (determined by mouth-to-limb contact).

[0133] Twitching / shaking: High-frequency shaking of the limbs (detected by rate of change of acceleration).

[0134] Freezing / stiffness: A sudden decrease in the amplitude of limb movement (by analysis of variance of movement trajectories).

[0135] Auxiliary judgment behavior:

[0136] (1) Stress response indicators:

[0137] Head turn: The animal's head suddenly turns towards the stimulated limb (tracked by head joint points).

[0138] Pupillary changes (if equipped with a near-infrared camera): Pupil dilation (autonomic nervous response related to pain).

[0139] (2) Overall activity status:

[0140] Basal movement baseline: The animal's natural activity (such as limb swing frequency) is recorded 30 seconds before the experiment to calibrate behavioral sensitivity.

[0141] Struggle intensity: The range of motion of the whole body (calculated by the displacement of the trunk joints), used to determine the effectiveness of the experiment (data will be invalidated if the struggle is excessive).

[0142] In an exemplary embodiment, the display screen 10 includes a parameter configuration area, a real-time data display area, and an operation control area.

[0143] The real-time data display area adopts a dual-window mode, with one window displaying a time-pressure change curve and the other window displaying animal behavior information.

[0144] In an exemplary embodiment, the parameter configuration area is used to configure the pressure increase rate, safety threshold, and number of experiments.

[0145] The operation control area includes a pause / start button, an alarm button and a data storage button.

[0146] In actual applications, the human-computer interaction interface (display screen 10) includes three major functional modules:

[0147] ① Parameter configuration area: Parameters are set via the display screen 10 on the PC side, and a graphical interface (GUI) is provided to set parameters such as the pressure increase rate (0.1N / s), safety threshold (such as 1.5N), and number of experiments.

[0148] ② Real-time data display area: adopts dual-window mode, with the pressure-time curve displayed on the left and the real-time image of the binocular camera (marking the joint points) on the right.

[0149] ③ Operation control area: including pause / start button (double-click to prevent accidental touch), alarm prompt area (over-limit sound and light alarm + emergency stop button, when the pressure exceeds the safety threshold or camera 5 loses focus, the sound alarm is triggered and the experiment is paused) and data storage button (supports CSV / JSON format).

[0150] In actual application, a signal converter 4 is provided in the shell 1 and connected to the automatic telescopic device. The signal converter 4 obtains the pressure signal of the probe of the pressure sensor 2, converts it into a voltage signal and transmits it to the display. The display displays continuous readings and draws a continuous time-pressure change curve; the camera 5 captures the picture and transmits it to the display screen 10 in real time after signal conversion, which is convenient for observing animal behavior information.

[0151] In practical applications, this application can achieve the following effects:

[0152] (1) The probe is combined with the pressure sensor 2 to effectively stimulate the joint and reflect the pressure changes in real time.

[0153] (2) The telescopic device automatically increases the pressure, effectively reducing errors caused by manual operation.

[0154] (3) Automatic telescopic device: Using precision cylinder as the telescopic structure, it significantly improves accuracy and reduces errors.

[0155] (4) It adopts a cylindrical "forehead thermometer" structure, which is easy to hold and simple to operate.

[0156] This application uses a precise cylinder automatic extension device to adjust the extension and retraction length of the pressure sensor 2 and probe, thereby measuring continuous pressure data. A high-resolution camera captures animal behavior information in real time, accurately determining the time of withdrawal behavior, and making the measurement of joint pain threshold more accurate. Furthermore, the present invention is designed as a handheld testing device, which has the advantages of being compact, portable, and easy to operate.

[0157] like Figure 4 As shown, the present application also provides a method for measuring the joint pain threshold of rodents, comprising:

[0158] S1: Based on the rodent joint pain threshold measurement device, continuously collected pressure signals and rodent behavioral images.

[0159] S2: Drawing a time-pressure variation curve according to the pressure signal.

[0160] S3: Capturing animal behavior information in real time according to the behavior image.

[0161] S4: Determine the time point when the rodent exhibits effective withdrawal behavior based on the animal behavior information.

[0162] S5: Based on the time-pressure change curve, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

[0163] In an exemplary embodiment, S4 specifically includes the following steps.

[0164] The limb joint points in the behavior image are marked in real time.

[0165] Based on the animal behavior information, it is determined that the rodent exhibits effective retreat behavior according to the current state of the limb joints and the pressure signal; the current state includes the angle change of the limb joints and the movement position of the limbs.

[0166] In an exemplary embodiment, determining whether the rodent exhibits effective retreat behavior based on the animal behavior information and the current state of the limb joints and the pressure signal specifically includes:

[0167] When the pressure signal shows a downward trend within a set time period, it is determined that the pressure drop amplitude is greater than a set amplitude threshold, and a first judgment result is obtained.

[0168] If the first judgment result is yes, it is determined that the rodent exhibits retreat behavior.

[0169] If the first judgment result is no, continue to collect the pressure signal.

[0170] It is determined whether the angle of the limb joint point is greater than or equal to a set angle threshold to obtain a second determination result.

[0171] If the second judgment result is yes, it is determined that the rodent exhibits retreat behavior.

[0172] If the second judgment result is no, continue to collect behavior images.

[0173] It is determined whether the limb movement position is greater than or equal to a set percentage threshold of a set reference position to obtain a third judgment result.

[0174] If the third judgment result is yes, it is determined that the rodent exhibits retreat behavior.

[0175] If the third judgment result is no, continue to collect behavior images.

[0176] According to the first judgment result, the second judgment result and the third judgment result, it is determined that the rodent exhibits effective retreat behavior.

[0177] In an exemplary embodiment, determining whether the rodent exhibits effective retreat behavior based on the first judgment result, the second judgment result, and the third judgment result specifically includes:

[0178] If the first judgment result is yes and the second judgment result is yes or the third judgment result is yes, it is determined that the rodent exhibits effective retreat behavior.

[0179] In practical applications, first of all, the original signal collected by the sensor, that is, the pressure signal, needs to undergo three processing steps:

[0180] (1) Calibration: Use the zero-point calibration method. When the probe does not touch the joint, it will automatically return to zero.

[0181] The fundamental role of calibration is to eliminate sensor zero drift and ensure an accurate measurement baseline. Without calibration, filtering and threshold detection will be based on an incorrect baseline, leading to misjudgment.

[0182] (2) Filtering: Use a low-pass filter to remove high-frequency noise (such as mechanical vibration and environmental electromagnetic interference). Use a sliding average filter to smooth the data and take the average of 10 consecutive sampling points to ensure that the pressure curve is continuous and stable.

[0183] Filtering can purify data and improve signal-to-noise ratio. Data purification: Low-pass filtering (suppresses high-frequency noise) and sliding averaging (smoothes short-term fluctuations) provide a stable signal for threshold detection. Improving the signal-to-noise ratio: Mechanical vibration or electromagnetic interference can cause pressure spikes. Filtered pressure curves are closer to actual biological responses.

[0184] (3) Threshold detection: A dynamic threshold algorithm is used to set a dynamic threshold range based on the baseline pressure, and behavior judgment is triggered when the range is exceeded.

[0185] The decision-making basis of threshold detection is: based on the calibrated and filtered signal, the threshold range is dynamically set to determine whether a pain response occurs.

[0186] Reliance on pre-processing: If calibration or filtering fails, threshold detection may trigger falsely.

[0187] Trigger behavior determination includes:

[0188] (1) Determination of effective retreat behavior:

[0189] When the pressure signal exceeds the dynamic threshold range, the system determines that the animal has a withdrawal reaction.

[0190] (2) Output pain threshold data:

[0191] The actual pressure value at the moment of triggering is recorded as the pain threshold. The associated timestamp, pressure curve segment, and visual behavior video are stored.

[0192] (3) Control response:

[0193] End pressure: Immediately stop the cylinder from advancing and the probe will automatically retract.

[0194] Alarm prompt: Trigger an audible and visual alarm or interface prompt to notify the experimenter to record the results.

[0195] The visual data processing process and the processed pressure signal are closely linked through multimodal data fusion and time synchronization, jointly ensuring the accuracy and reliability of pain threshold determination.

[0196] 1) Time synchronization and event triggering:

[0197] (1) Timestamp alignment: The pressure sensor data and binocular vision data need to be timestamped by a unified clock source to ensure that the two are strictly synchronized on the time axis.

[0198] (2) Joint trigger mechanism:

[0199] Pressure signal triggers visual analysis: When the pressure drops suddenly, the visual system automatically extracts the image sequence within the time window (such as 100ms before the trigger to 100ms after the trigger) for detailed behavioral analysis.

[0200] Visual signals assist pressure determination: If joint displacement is detected visually but the pressure does not exceed the threshold (such as the animal struggling in advance), the system marks it as invalid data to eliminate interference.

[0201] 2) Data fusion and behavior determination:

[0202] (1) Multimodal input fusion:

[0203] Pressure-displacement curve: The pressure signal (time-pressure curve) is superimposed with the visual data (time-joint displacement curve) to verify the spatiotemporal consistency of the pain response.

[0204] Compound judgment conditions:

[0205] Pressure conditions: Pressure drop ≥ 20% of baseline value (from pressure treatment step 3).

[0206] Visual conditions: joint angle change >15° or displacement >10% (from visual processing step 2).

[0207] Logical relationship: Only when both conditions are met at the same time can it be determined as an effective pain threshold.

[0208] (2) Dynamic threshold calibration:

[0209] Visual data is used to dynamically adjust pressure thresholds. For example, if an animal frequently flinched in small steps (visually detected displacement but pressure below the threshold), the system could automatically reduce the pressure increase rate to avoid overstimulation.

[0210] 3) Algorithm collaborative optimization:

[0211] (1) Visually assisted pressure filtering:

[0212] Visual data can identify external interference and mark abnormal time periods, and the pressure filtering algorithm dynamically adjusts the filtering parameters accordingly.

[0213] (2) Pressure data guides visual analysis area:

[0214] The contact position of the pressure sensor 2 is mapped through coordinates to guide the binocular camera to focus on a specific joint point, reducing the computational complexity of image processing.

[0215] The visual data (i.e. behavioral images) processing process is as follows:

[0216] (1) Binocular vision depth calculation: ① View difference generation: The SGBM algorithm in OpenCV is used to generate view difference. The OpenCV SGBM example configuration (for a 200fps binocular camera) is as follows:

[0217] sgbm = cv2.StereoSGBM_create(

[0218] minDisparity=0, #minimum disparity (usually 0)

[0219] numDisparities=64, #disparity search range (must be an integer multiple of 16, 64-128 is recommended)

[0220] blockSize=11, #match block size (odd number, 7-15 is recommended)

[0221] P1=8*3*blockSize**2, #smoothing penalty coefficient 1 (edge ​​sensitivity)

[0222] P2=32*3*blockSize**2, #smoothing penalty coefficient 2 (continuity sensitivity)

[0223] disp12MaxDiff=1, #maximum allowable difference in left and right parallax check

[0224] uniquenessRatio=15, #uniqueness ratio (to suppress false matches)

[0225] speckleWindowSize=100, #window size for filtering out isolated noise points

[0226] speckleRange=2 #parallax change threshold )

[0228] numDisparities: needs to cover the actual disparity range; blockSize: the smaller the value, the more details are retained, but it is sensitive to noise; too large a value leads to blurred edges.

[0229] ② Disparity post-processing: Use WLS filtering (weighted least squares) to smooth the disparity map.

[0230] ③ Stereo correction: Use the Bouguet algorithm to align the camera epipolar lines to reduce matching errors.

[0231] The relationship between the stereo-corrected disparity map and the subsequent behavior recognition algorithm is as follows:

[0232] 1. 3D motion trajectory reconstruction:

[0233] (1) The core role of disparity map:

[0234] The stereo-rectified disparity map provides depth information for each pixel in the scene (Z = f × B / d, f is the focal length, B is the baseline distance, and d is the disparity).

[0235] (2) Three-dimensional positioning of joint points:

[0236] The behavior recognition algorithm maps the joint points in the two-dimensional image to three-dimensional space coordinates through the disparity map of binocular vision.

[0237] 2. Motion feature extraction:

[0238] (1) Calculation of three-dimensional displacement and angle:

[0239] Displacement: Calculate the distance the limb moves by changing the three-dimensional coordinates of the joints between consecutive frames.

[0240] Joint Angle: Calculates joint flexion / extension angles based on 3D coordinates.

[0241] (2) Dynamic feature enhancement:

[0242] The depth information provided by the disparity map can distinguish real actions from environmental noise and improve the robustness of feature extraction.

[0243] 3. Multimodal data fusion:

[0244] (1) Collaboration between disparity map and pressure signal:

[0245] When the pressure sensor 2 detects a sudden drop in pressure (such as a trigger threshold), the algorithm synchronously extracts the disparity map at the corresponding time point and analyzes the three-dimensional motion trajectory of the joint.

[0246] (2) Joint judgment: Only when the pressure change and the three-dimensional displacement / angle change meet the conditions at the same time, it is judged as an effective pain response.

[0247] The behavior recognition algorithm is as follows:

[0248] (1) Key point tracking: Use lightweight OpenPose to mark limb joints (such as hip, knee, and ankle) in real time.

[0249] (2) Criteria for withdrawal: Animal withdrawal behavior is determined when there is a sudden drop in pressure (a drop of more than 20% within 5 ms); a change in joint angle >15° (such as knee flexion); and a limb displacement >10% of the reference position (the coordinate at the time of initial contact).

[0250] (3) Algorithm output: Combining the pressure signal and visual data, when both meet the threshold conditions at the same time, it is determined to be an effective withdrawal behavior, and the current pressure probe pressure value is output as the test joint pain threshold, such as Figure 5 shown.

[0251] Furthermore, during the measurement process: (1) Use a flexible joint clamp (the clamp is covered with animal fur on the surface to reduce the animal's stress response) to fix the mouse joint and expose the part to be measured. (2) Place the probe of the measuring device close to the joint to be measured, contact it but do not apply pressure. (3) Turn on the device, adjust the parameters, start the automatic retraction system, and the pressure of the probe head continues to increase. At the same time, a time-pressure curve is drawn in real time on the display screen 10. (4) When the pressure increases to the point where the animal shows withdrawal behavior, read the pain threshold reading, and review the video of camera 5 to verify the time point when the animal's withdrawal behavior occurs and confirm the reading. (5) Repeat the experiment to avoid contingency. The experimental process timing diagram is as follows. Figure 6 shown.

[0252] The technical features of the above embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0253] This document uses specific examples to illustrate the principles and implementation methods of this application. The description of the above examples is only intended to help understand the method and core concept of this application. At the same time, for those skilled in the art, based on the concept of this application, there may be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as limiting this application.

Claims

1. A device for measuring joint pain threshold in rodents, characterized in that: include: case; A pressure sensor is movably connected to the housing, and an automatic telescopic device is provided inside the housing; a pressure sensing probe is provided on the pressure sensor; the pressure sensing probe is used to apply pressure to the rodent's joint; the automatic telescopic device is connected to the pressure sensor and is used to adjust the telescopic length of the pressure sensor and the pressure sensing probe; The pressure sensor is connected to the display screen via a signal converter in the housing, and is used to upload the pressure signal continuously collected by the pressure sensing probe to the display screen; The housing is provided with a camera; the camera is connected to the display screen via the signal converter, and is used to capture behavioral images of rodents, capture animal behavior information in real time, and upload it to the display screen; The display screen is used to display the time-pressure change curve and animal behavior information; Based on the time-pressure variation curve and the animal behavior information, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

2. The rodent joint pain threshold measuring device according to claim 1, characterized in that: The automatic telescopic device specifically includes: a telescopic cylinder, a pneumatic regulating valve, and a compressed gas box connected through a standardized interface; The telescopic cylinder is connected to the pressure sensor and is used to drive the pressure sensor to extend and retract to adjust the telescopic length of the pressure sensing probe; The pneumatic regulating valve is provided with a telescopic control button, and the pneumatic regulating valve is used to adjust the amount of gas entering the telescopic cylinder to adjust the air pressure in the telescopic cylinder; The compressed gas tank is used to store compressed gas.

3. The rodent joint pain threshold measuring device according to claim 2, characterized in that: An incremental PID algorithm is used to adjust the air pressure in the telescopic cylinder.

4. The rodent joint pain threshold measuring device according to claim 1, characterized in that: The camera is a binocular stereo vision camera; The frame rate of the binocular stereo vision camera is 200fps.

5. The rodent joint pain threshold measuring device according to claim 1, characterized in that: The display screen includes a parameter configuration area, a real-time data display area and an operation control area; The real-time data display area adopts a dual-window mode, with one window displaying a time-pressure change curve and the other window displaying animal behavior information.

6. The rodent joint pain threshold measuring device according to claim 5, characterized in that: The parameter configuration area is used to configure the pressure growth rate, safety threshold and number of experiments; The operation control area includes a pause / start button, an alarm button and a data storage button.

7. A method for measuring joint pain threshold in rodents, characterized in that: include: Based on the rodent joint pain threshold measurement device according to claims 1-6, continuously collected pressure signals and rodent behavior images; Drawing a time-pressure change curve according to the pressure signal; capturing animal behavior information in real time based on the behavior image; determining, based on the animal behavior information, a time point at which the rodent exhibits effective withdrawal behavior; Based on the time-pressure change curve, the pressure value of the pressure sensor probe corresponding to the time point when the rodent exhibits effective withdrawal behavior is used as the pain threshold of the rodent's joint.

8. The method for measuring the joint pain threshold of rodents according to claim 7, characterized in that: Determining the time point at which the rodent exhibits effective withdrawal behavior based on the animal behavior information specifically includes: marking limb joints in the behavioral image in real time; Based on the animal behavior information, it is determined that the rodent exhibits effective retreat behavior according to the current state of the limb joints and the pressure signal; the current state includes the angle change of the limb joints and the movement position of the limbs.

9. The method for measuring the joint pain threshold of rodents according to claim 8, characterized in that: Determining, based on the animal behavior information and according to the current state of the limb joints and the pressure signal, that the rodent exhibits effective retreat behavior, specifically includes: When the pressure signal shows a downward trend within a set time period, it is determined that the pressure drop amplitude is greater than a set amplitude threshold, and a first determination result is obtained; If the first judgment result is yes, determining that the rodent exhibits retreat behavior; If the first judgment result is no, continue to collect the pressure signal; Determine whether the angle of the limb joint is greater than or equal to a set angle threshold, and obtain a second determination result; If the second judgment result is yes, determining that the rodent exhibits retreat behavior; If the second judgment result is no, continue to collect behavioral images; determining whether the limb movement position is greater than or equal to a set percentage threshold of a set reference position, to obtain a third determination result; If the third judgment result is yes, determining that the rodent exhibits retreat behavior; If the third judgment result is no, continue collecting behavior images; According to the first judgment result, the second judgment result and the third judgment result, it is determined that the rodent exhibits effective retreat behavior.

10. The method for measuring the joint pain threshold of rodents according to claim 9, characterized in that: Determining, based on the first judgment result, the second judgment result, and the third judgment result, that the rodent exhibits effective retreat behavior specifically includes: If the first judgment result is yes and the second judgment result is yes or the third judgment result is yes, it is determined that the rodent exhibits effective retreat behavior.