Table 1.

Experimental methods of pain assessment in rodent arthritis models

Assessment method [example references]	Response measured	Pain aspect assessed	Advantages	Disadvantages
Von Frey test/mechanical hyperalgesia [6, 32, 33, 48–54, 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, 56–59, 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, 61–66]	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

CNS central nervous system, fMRI functional magnetic resonance imaging