In vivo Pain Studies

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 relevant models for acute pain and chronic pain.

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 animal models that have been validated using existing and novel methods to effectively test new therapeutic candidates.

Acute or 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 Acute phasic pain where the stimulus can be withdrawn is typically measured using the following well-studied protocols: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

line graph showing two phases of pain measured after exposure to 5% formalin

Chronic and 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.

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

Bar graph showing increased paw latency in response to diclofenac in a dose dependent manner

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 models of neuropathic pain are typically evaluated in a stimulus-response setting. Pharmacology and efficacy studies using the following animal models of neuropathic pain are available at Charles River:

Nerve constriction/ligation models include:

Chemotherapy-induced models include:

Diabetic neuropathy models include:

  • Streptozotozin (STZ)-induced model

The models of neuropathic pain 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 model

Bar graph showing increased response to the anti-epileptic pregabalin in a spinal nerve ligation model of neuropathic pain

Check out some of the frequently answered questions on in vivo pain pharmacology studies and assays.