Table 2.

Preclinical studies assessing age-related differences in pain processing and behavior (2000 – present).

Pain model	Rodent strain	Male (M) or female (F)	Age of rodent		Nociception in aging	Changes in aging rodents	Reference
			Young (Months/Specified)	Old (Months/Specified)	No Change, Increase, or Decrease
Hot-plate	Mice C57BL/6J under genetically controlled condition	M	2–11	17–23	Increase	Reduced hot plate latency	146
Hot-plate	Mice C57BL/6J	M & F	1.5	15	Decrease	Longer thermal latency	74
				24
Hot-plate	Mice C57BL/6J	M & F	1.5–2	24	Decrease	Decreased thermal sensitivity	131
Hot-plate	Mice C57BL/6J	M	2–8	12	No change	Similar thermal latency	147
Hot-plate	Mice 129Sv/Ev	M	4–11	24	Increase	Increased pain sensitivity (decreased pain threshold)	148
Hot-plate	Mice deletion of p66Shc in 129Sv/Ev	M	4–11	24	Decrease	Decreased pain sensitivity (increased pain threshold)	148
Hot-plate	Rat fischer 344/DuCrj	M	7–13	29–34	Decrease	Less paw licking behavior	133
Hot-plate	Rat fischer 344/DuCrj	M	7–13	29–34	Increase	Shorter thermal withdrawal latency	133
Hot-plate	Rat long -evans	F	8	32	No change	No change in paw-licking behavior to heat	134
Thermal escape (hot)	Rat long -evans	F	8	32	Increase	Increased thermal sensitivity (escape)	134
Thermal escape (cold)	Rat long -evans	F	8	32	Increase	Increased cold sensitivity (escape). Of note, is greater sensitivity to cold versus heat	134
Formalin test 20 µL of 5% formalin subcutaneous dorsal surface hindpaw	Mice C57BL/6	M & F	1.5–2	12	Decrease	Reduced nociceptive response in aged mice	144
Formalin test (20 µL of 5% FormalinSubcutaneous left hindpaw)	Mice C57BL/6	M	2–6	13–20	Increase	Temporal shift with an increase in the peak amplitudes	145
Formalin test (10 µL (young) and 50 µL (old) of 1.25%, 1.75%, and 2.25% formalin right hindpaw)	Rat wistar	M & F	7–13–22 days	82 days	Increase	At 82 days, both males and females showed biphasic patterns in response to 3 formalin concentrations	149
Formalin test (50 µL of 5% formalin subcutaneous dorsal hindpaw)	Rat long-evans	F	8	16	Increase	Increased sensitivity to thermal stimulation	134
				24
Complete freund adjuvant (CFA) (30 µL of CFA subcutaneous left hindpaw)	Mice C57BL/6	M	2	>18	Increase	Young and old mice exhibit high pain behavior during acute (2 days) and chronic (8 weeks) inflammation. However, young mice exhibit higher sensitization to mechanical stimuli	73
Complete freund adjuvant (CFA) (30 µL of CFA subcutaneous left hindpaw)	Rat sprague-dawley	M	3	18	Increase	Increased thermal sensitivity at 48 h following CFA	141
Complete freund adjuvant (CFA) (50 µL of CFA subcutaneous left hindpaw)	Rat Fisher 344/DuCrj	M	7–12	29–34	No change	Aged rats showed enhanced peripheral inflammatory responses to CFA with only a slight change in dorsal horn neuronal activity	140
Chronic constriction model	Rat fischer 344/FBNF1	M	4–6	24–26	Decrease	Decreased allodynic response on von-frey	137
Chronic constriction injury	Rat fischer F344 BNF1 hybrid	M	4–6	14–16	Decrease	Temporal shift with slower development of thermal hyperalgesia and tactile allodynia after injury	142
				24–26
Chronic constriction injury	Rat fischer 344/FBNF1 hybrid	M	4–6	14–16	Decrease	Temporal shift with slower development of thermal hyperalgesia and tactile allodynia after injury	143
				24–26
Chronic constriction model	Rat lou/cjall	M	4–6	20–22	Increase	Old and senescent rats are more sensitive to acute pain	138
				37–39
IAN transection	Rats sprague -dawley rats	M	9	>29	Increase	Increased background activity and activity following response to mechanical stimulus in the dorsal horn of aged rats	136
Plantar incision	Rat fischer 344/FBNF1 hybrid	M & F	3–6	>22	Decrease	Aged males showed reduced mechanical hypersensitivity	150