Pain Studies

Pain Studies

Charles River conducts several hundred disease model studies on candidates targeting various types of pain including acute pain, inflammatory pain and neuropathic pain. We have developed a variety of clinically relevant pain models that have been validated using existing and novel methods to effectively test new therapeutic candidates.

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Neuroscience 2019 Scientific Posters
 

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Acute and chronic pain management therapies are a major segment in neurological drug discovery, and many types of pain are still devoid of effective treatment. New pain-focused candidates are constantly being identified – in 2016, 11 new pain-focused candidates were identified. Interestingly, therapies that effectively block acute pain often produce poor results in chronic pain conditions, so it is essential to test candidates in pain studies using relevant models for acute and chronic pain.

Acute Pain Models/Nociceptive Pain Models

Acute pain is defined as a normal physiological response to external noxious stimuli and serves as a protective early warning system for the body. Acute phasic pain where the stimulus can be withdrawn is typically measured using the following well-studied protocols:

• Tail flick test
• Hargreaves thermal test
• Hot plate test
• Paw pressure test
• Pin-prick test

Acute tonic pain where there is short stimuli is typically measured using the following tests:

• Formalin test
• Acetic acid writhing test
• Capsaicin test

Figure 1: Bi-phasic nocifensive behavioral response in response to formalin exposure in an acute pain model.

Chronic Pain Models/Inflammatory Pain Models

Inflammatory pain is usually caused by tissue injury, arthritis, or tumor growth. Tissues that are damaged due to infection, tumor growth, or injury typically show an inflammatory response, which triggers a pain reaction. Pro-inflammatory molecules activate nociceptors evoking responses such as allodynia and hyperalgesia. Inflammatory pain models target both acute and chronic inflammatory pain depending on the stimulus that includes carrageenan and capsaicin.

• Chronic joint pain models including MIA, gout pain, and arthritic pain
• Acute inflammatory pain models
  • Complete Freund’s Adjuvant (CFA)
  • Carrageenan inflammation model (paw edema)
  • Zymosan paw edema
  • Intra-colonic capsaicin
  • Paw incision post-op pain
• Peripheral neuroinflammation model using CFA induce neuroinflammation

Figure 2: Effect of diclofenac on the rat CFA Neuroinflammation model measure using heat hyperalgesia

Diclofenac increases the paw withdrawal latency in a dose dependent manner.

Neuropathic Pain Models

Neuropathic pain is typically found in about 7-8% of the global population and is commonly detected as a secondary disease in cancer (chemotherapy induced) and diabetes. Neuropathic pain is characterized by dysesthesias (numbness, stabbing, and burning sensations) and allodynia. Rodent neuropathic pain models are typically evaluated in a stimulus-response setting. Pharmacology and efficacy studies using the following neuropathic pain models are available at Charles River:

Nerve constriction/ligation neuropathic pain models include:

• Spinal nerve ligation model (SNL)
• Chronic constriction model (CCI)
• Spared nerve Injury model (SNI)
• Partial sciatic nerve ligation model (PSNL)

Chemotherapy-induced neuropathic pain models include:

• Oxaliplatin-induced model

Diabetic neuropathic pain models include:

• Streptozotozin (STZ)-induced model

The neuropathic pain models are validated using the following established assays, and our scientific team is developing new endpoints to measure gait and balance changes in response to pain stimuli.

Mechanical stimulation include:

• Von Frey filament test
• Electronic von Frey
• Paw pressure test
• Pinprick test

Thermal stimulation include:

• Tail flick/tail immersion test (cool allodynia)
• Acetone test (cool allodynia)
• Hargreaves test (warm/heat allodynia)
• Hot/cold plate

Figure 3: Effect of pregabalin (anti-epileptics) on a nerve ligation Neuropathic pain model

Check out some of the frequently answered questions on pharmacology studies and assays using pain models.