Neuropathic Pain Nonhuman Primates Disease Model

Explores the challenges of pain research and introduces the Non-Human Primate (NHP) pain model as a promising solution. Learn about the advantages of NHPs for studying pain, the design of chronic and acute pain models, and key results showcasing their effectiveness.

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Product Introduction

Pain is defined by the International Association for the Study of Pain (IASP) as an "unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain is not homogenous and can be categorized into at least four different types based on their causes: nociceptive, inflammatory, neuropathic, and idiopathic pain. These types of pain tend to differ in their time courses. Nociceptive and inflammatory pain are usually short-term (transient or acute pain), whereas neuropathic and idiopathic pain often last for years or even indefinitely (chronic pain).

Acute or physiological pain serves as an early warning against potential injury and is a vital defense mechanism. In contrast, chronic pain does not play a useful role and can adversely affect general and psychological health. This is evident from the high degree of comorbidity between chronic pain and emotional disorders such as depression and anxiety. Chronic pain, especially neuropathic pain, is characterized by sensory abnormalities such as abnormal unpleasant sensations (dysesthesia), increased intensity of response to painful stimuli (hyperalgesia), and pain in response to normally painless stimuli (allodynia).

Published estimates of the prevalence of chronic pain typically range from 2% to 45%. However, creating more efficacious medications for pain control remains a significant challenge. This is primarily due to the heterogeneity of the condition itself, including the causes and underlying pathologies, redundancies in pain perception, and the usefulness of current pharmacological therapies.

Advantages of NHP Pain model

Current pain models in non-primate animals like rodents rely heavily on assessing pain or hypersensitivity-induced pain behaviors. These behaviors include spinal reflexes (such as withdrawal from experimenter-applied stimuli), spino-bulbospinal reflexes (such as jumping or abdominal stretching), or simple innate behaviors (such as vocalization, scratching, biting, licking, and guarding). An over-reliance on measures of hypersensitivity may lack clinical face validity.

Non-human primates (NHPs) not only exhibit pain behaviors that are more similar to humans, but they can also perform complex cognitive tasks to communicate their suffering. Most importantly, the physiological and anatomical similarities between NHPs and humans provide a more accurate platform for evaluating the efficacy and safety of new analgesics, improving the chances of successful translation from preclinical studies to human clinical trials.

Study design and clinical endpoints

Chronic Pain Model：

Partial Sciatic Nerve Ligation (PSNL) model

•Loose ligation of superficial peroneal nerve

•Pros:

•Reliable, easily reproduce

•Post-traumatic peripheral pain mimicry

•Partial denervation

•Inflammatory and neuropathic combination

•Suitable for cold allodynia

Acute Pain Model:

Formalin finger-injection Model

•Injection of a small amounts of 5% formalin subcutaneously into the paw

•Pros:

•Minimal tissue damage

•Restrict pain to the experimental period

•Two pain phases: nociceptors activation + inflammatory

•Assess nociception and inflammation-related responses

Standard scalp-EEG and EMG — State-of-the-art Technologies and Innovation to Overcome the Challenges on Signal Detection in NHP

Primary Endpoints:

1.Behavioral analysis: AI-based 3D Behavior Analysis , Gait analysis

2.Mechanical hyperalgesia: Pressure application measurement (PAM)

3.Thermal hyperalgesia and allodynia: heat test and cold test

4.Indicators of voluntary reactions: conditioned place aversion/preference (CPA/CPP) (In progress)

5.Pupil response (In progress)

Secondary Endpoints

1.Classic positive drug treatment

2.Facial expression: Grimace scales (In progress)

3.EEG/EMG recording

4.Sleep-wake cycles

Locomotor activity

key result and figure legend

Sensory system test for NHP pain model. (A) The difference in withdrawal thresholds to mechanical pressure stimulation between the modeled side (Liga) and the control side (Ctrl) at different time points (Ctrl - Liga). (B) The difference in withdrawal latency to heat stimulation (hot plate) between the modeled side (Liga) and the control side (Ctrl) at different time points (Liga - Ctrl). (C) The difference in withdrawal latency to cold stimulation (cold water) between the modeled side (Liga) and the control side (Ctrl) at different time points (Ctrl - Liga). Values greater than zero (red for A and B) indicate a decrease in withdrawal threshold and hyperalgesia, while values less than zero (blue for A and B) indicate an increase in withdrawal threshold and dysesthesias.

AI-based 3D Behavior Analysis of 2-hour video for acute pain model animal (N=2). Acute pain model show a classic two phases of pain behavior in sit, walking, hang, and crouch behavior.

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