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Table 1 Experimental methods of pain assessment in rodent arthritis models

From: Animal models of rheumatoid pain: experimental systems and insights

Assessment method [example references]

Response measured

Pain aspect assessed

Advantages

Disadvantages

Von Frey test/mechanical hyperalgesia [6, 32, 33, 48,49,50,51,52,53,54, 56, 58, 59, 62]

Pain-evoked behavior: withdrawal threshold from a mechanical stimulus

Mechanical allodynia/hyperalgesia

Quantitative, well-established protocols

Stimulation of mechanical and nociceptive fibers; possible investigator bias/subjectivity

Hargreaves test/thermonociception [6, 33, 51, 53, 54, 56,57,58,59, 62]

Pain-evoked behavior: withdrawal latency from a thermal stimulus

Thermal allodynia/hyperalgesia

Quantitative, well-established protocols; primary stimulation of nociceptive fibers

Possible investigator bias/subjectivity

Ambulatory/locomotor behavior [53, 56, 59, 61,62,63,64,65,66]

Pain-suppressed behavior: locomotion in an open field

Locomotor activity/ambulation/exploratory behavior

Automated quantitative measurement; may include affective component

May be affected by nonpain-related outcomes (e.g., motor function)

Grimace scales [38]

Changes in facial expressions associated with pain

Expression of subjective pain perception

Non-interventional; directly linked to individual pain state; may include affective component

Possible investigator bias/subjectivity; experimenter training needed; further validation in arthritis models required

fMRI [6]

Functional changes in CNS activity associated with pain

Affective CNS responses to pain

Objective measurements; may include affective component

Expensive equipment; high-level investigator training needed; requirement for restraint/sedation

Gait/dynamic weight bearing analysis [34, 59]

Changes in ambulatory posture or weight distribution

Spontaneous gait changes due to joint pain

Objective, quantitative measurements; automated systems available

Specialized equipment needed.

Operant conditioning [60]

Behavior emitted to receive a reward despite concurrent exposure to a painful stimulus

Affective and/or motivational components of pain perception

Objective, quantitative; automated systems available; may include affective component

Specialized equipment needed

Escape/avoidance [45]

Latency to escape noxious stimulus

Affective and/or motivational components of pain perception

Objective, quantitative; automated systems available; may include affective component

Specialized equipment needed

  1. CNS central nervous system, fMRI functional magnetic resonance imaging