Mechanical Sensitivity
- Electronic Von Frey test to determine paw withdrawal threshold
- Manual Von Frey filament test
- Pin-Prick score assessment
- Dynamic mechanical allodynia by brushing test score
Pain Drug Discovery Services
Our pain drug discovery services support biotechnology and pharmaceutical companies with preclinical pharmacology, efficacy studies, and model-based decision making across acute, inflammatory, and neuropathic pain indications.
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Pain Studies
Pain remains one of the largest unmet medical needs across neurology, inflammation, oncology, and rare diseases. Despite substantial investment in analgesic development, many therapeutic candidates fail because efficacy observed in early studies does not translate into meaningful clinical benefit. Advancing novel pain therapies requires translational models and innovative readouts that accurately reflect disease mechanisms and predict clinical outcomes.
We partner with you from target validation through candidate selection, providing robust in vitro assays, in vivo pain models, behavioral and imaging endpoints, and integrated study strategies designed to accelerate the development of innovative analgesics. Our capabilities span acute nociceptive pain, chronic inflammatory pain, neuropathic pain, and neuroinflammatory disorders.
Our scientific team applies a clinic-led approach to pain drug discovery by combining validated disease models with clinically relevant endpoints. Study designs are tailored to the mechanism of action, target biology, and therapeutic hypothesis of each program, providing actionable data to support candidate progression. Through integrated pharmacology services, sponsors can evaluate efficacy, optimize dosing strategies, characterize biomarkers, and generate the confidence needed to advance development decisions.
Preclinical Pain Models
We offer a comprehensive portfolio of validated pain models to support discovery and translational research across multiple therapeutic modalities, including small molecules, biologics, gene therapies, and novel analgesic modalities. Pain disorders are generally classified according to their underlying biological mechanisms, and each presents unique challenges for therapeutic development and requires different preclinical models and translational strategies
Acute and Inflammatory Pain Models
Nociceptive acute pain is a short-term, sharp, or aching physical response triggered when specialized nerve endings detect actual or potential tissue damage from an injury, burn, or inflammation. Pain pathways are activated when physical, thermal, or chemical harm activates pain receptors (nociceptors). It typically lasts for a limited period and resolves as healing occurs. Acute and inflammatory pain models are widely used in pain drug discovery to evaluate the immediate effects of therapeutic candidates on acute pain responses and sensory processing pathways. These models involve subcutaneous injection of an irritant or inflammatory agent, and each have a slightly different recommended purpose.
Formalin Model
Capsaicin Model
Carrageenan Model
CFA (Complete Freund's Adjuvant) model
Formalin Model
- Common acute inflammatory pain model
- Allows for rapid screening of novel analgesics
- Also used as a pain response test in neuropathic pain models
- Triggers a highly reproducible biphasic pain response within 60 minutes
- Phase I (0-10 minutes): acute neurogenic pain caused by direct activation of primary C-fibers.
- Phase II (15–60 min): tonic inflammatory pain driven by central sensitization in the spinal cord
- Centrally acting drugs, such as opioids inhibit both phase I and II, where peripherally acting drugs, such as NSAIDs only inhibit phase II
- Spontaneous behaviors, including paw flinching, licks and bites, are assess as a primary readout
Capsaicin Model
- Common acute inflammatory pain models with secondary central sensitization and hyperalgesia
- Triggers a rapid, short-lasting chemogenic pain, with temporary thermal and mechanism hypersensitivity
- Model of choice for compounds targeting TRPV1 receptors, due to the activation of TRPV1 receptors on C-fiber nociceptors by capsaicin
Carrageenan Model
- Model of inflammatory pain response
- Triggers local immune response mediated by histamine, bradykinin, and prostaglandins, generating severe local edema alongside mechanical allodynia and thermal hyperalgesia
- Response peaks rapidly at 3 to 6 hours, and subsides within 24 hours
- Model of choice for therapeutics targeting inflammation and immune response in the context of pain
CFA (Complete Freund's Adjuvant) Model
- Model of sustained inflammatory pain response
- Mycobacterium particles in CFA induce a sustained immune response, resulting in localized tissue injury, swelling, and severe hypersensitivity
- Symptoms peak at 24–48 hours and persist for days to weeks
- Model of choice when investigating therapeutic effects against long-term inflammatory pain
Neuropathic Pain Models
Neuropathic pain presents unique translational challenges and frequently requires specialized disease models and endpoints. Neuropathic pain arises from injury or dysfunction within the peripheral or central nervous system. Common causes include diabetic neuropathy, chemotherapy-induced peripheral neuropathy, traumatic nerve injury, and neurological diseases.
Patients frequently experience symptoms such as burning sensations, allodynia, numbness, and chronic spontaneous pain. Neuropathic pain remains one of the most difficult pain conditions to treat, highlighting the need for more predictive preclinical models and innovative therapeutic approaches.
Pain Pharmacology Endpoints
Our pain drug discovery studies incorporate validated functional and behavioral endpoints to quantify treatment effects and support translational decision making. Beyond assessment of acute pain responses, advanced endpoint options including gait analysis, in vivo imaging, biomarker measurements, provide deeper insight into therapeutic response.
Mechanical Sensitivity
Thermal Sensitivity
Thermal Sensitivity
- Hargreaves test (plantar test) to determine paw withdrawal latencies
- Acetone cooling test to measure cold allodynia
- Hot and cold plate tests to measure temperature of paw withdrawal and withdrawal latency times
Advanced Endpoints
Advanced Endpoints
- Fine motor kinematic and gait analysis
- In vivo imaging
- Functional ultrasound imaging (fUS) imaging of neurovascular coupling upon mechanical stimulation)
- PET/SPECT imaging of inflammation
- in vivo or ex vivo MRI to evaluate nerve structure, demyelination and edema
- Electrophysiology assessment of nerve conduction velocity (NCV) and sensory nerve action potential (SNAP)
Translational Biomarkers
Translational Biomarkers
- Plasma inflammatory cytokine panels
- Markers of nerve degeneration in plasma or CSF
- in vivo and ex vivo measurement of neurochemical mediators in spinal cord (microdialysis of spinal cord dorsal horn) or plasma
- Intra-epidermal nerve fiber density (IENFD) in skin biopsies to examine small-fiber neuropathy and degeneration
- Evaluation of gene expression changes in specific tissues such as DRGs and spinal cord
Why Partner With Us
Our pain drug discovery team combines therapeutic area expertise, model development experience, and translational pharmacology capabilities to support successful program advancement.
We help clients:
- Select the most appropriate pain model for their mechanism
- Design studies aligned with clinical objectives
- Generate reproducible efficacy data
- Reduce development risk through informed decision making
- Accelerate candidate selection and IND-enabling progression
Understanding Pain Drug Discovery
Pain is a complex biological response that serves an essential protective function, alerting the body to actual or potential tissue damage. While acute pain is typically self-limiting and resolves as healing occurs, chronic pain can persist long after the original injury or disease has subsided, creating a significant burden for patients, healthcare systems, and society.
More than a symptom, chronic pain is increasingly recognized as a disease state driven by dynamic interactions between the peripheral nervous system, central nervous system, immune system, and inflammatory pathways. These interactions can lead to maladaptive changes in pain signaling that amplify sensory responses and contribute to long-term pain persistence.
The Biology of Pain
Challenges in Pain Drug Discovery
The Need for Translational Pain Research
The Biology of Pain
Pain perception begins when specialized sensory neurons, known as nociceptors, detect harmful mechanical, thermal, or chemical stimuli. These signals are transmitted through peripheral nerves to the spinal cord and brain, where they are processed and interpreted as pain. Understanding these mechanisms is essential for developing targeted therapies capable of delivering meaningful and durable pain relief.
Key biological mechanisms involved in pain include:
- Peripheral sensitization caused by inflammatory mediators released at the site of injury
- Central sensitization resulting from increased excitability within spinal and brain pain pathways
- Neuroimmune activation involving interactions between neurons, microglia, and immune cells
- Altered ion channel activity that changes neuronal excitability
- Dysregulation of neurotransmitters involved in pain transmission
Challenges in Pain Drug Discovery
Despite substantial advances in neuroscience and pharmacology, the development of novel pain therapeutics remains associated with high attrition rates. Many compounds demonstrate efficacy in early research but fail to generate meaningful clinical outcomes.
Several factors contribute to these challenges, including:
- Complex and heterogeneous disease mechanisms
- Differences between patient populations and disease subtypes
- Limited predictive value of some preclinical endpoints
- Difficulties in measuring subjective pain experiences clinically
- The need to balance efficacy with safety and tolerability
Addressing these challenges requires the integration of translationally relevant disease models, clinically meaningful endpoints, and a deep understanding of pain biology throughout the discovery process.
The Need for Translational Pain Research
As the understanding of pain mechanisms continues to evolve, drug developers are increasingly focusing on targeted approaches that address specific biological drivers of disease rather than simply suppressing symptoms.
The development of effective pain therapeutics remains challenging due to the diverse mechanisms underlying pain disorders and the variability in patient responses to treatment. As a result, translational preclinical models play a critical role in understanding disease biology, identifying novel therapeutic targets, and evaluating candidate medicines before clinical development
Modern pain drug discovery programs may target:
- Neuroinflammation pathways
- Ion channels and sensory neuron signaling
- Neuroimmune interactions
- Peripheral nerve regeneration
- Central sensitization mechanisms
- Novel non-opioid analgesic pathways
Translational pain research bridges the gap between fundamental biology and clinical development by leveraging validated animal models, functional endpoints, and mechanism-driven study designs. These approaches provide the data needed to prioritize promising candidates and improve the probability of clinical success.
Frequently Asked Questions about Pain Drug Discovery
What is pain drug discovery?
Pain drug discovery is the process of identifying, optimizing, and evaluating new therapeutic candidates intended to treat acute, chronic, inflammatory, or neuropathic pain.
What preclinical models are used in pain drug discovery?
Common models include acute nociceptive pain models, inflammatory pain models, arthritis pain models, neuroinflammation models, and neuropathic pain models such as SNI, SNL, CCI, and PSNL.
What endpoints are used to assess pain in preclinical studies?
Endpoints commonly include mechanical and thermal sensitivity measurements such as Von Frey testing, hot plate assays, Hargreaves testing, and paw pressure assessments.
How do preclinical pain studies support analgesic development?
Preclinical studies provide evidence of efficacy, characterize dose response, support mechanism validation, and guide candidate selection before clinical development.
