Table 3.
Rodent models of neonatal pain and times of assessment.
| “1-Hit” Models | |||
|---|---|---|---|
| 1st Stimulus (age) | Outcome measure(s) | Age/Time | References |
| INFLAMMATORY PAIN | |||
| CFA (P1) |
PWL EPM, PWL, sleep recordings, ACTH, corticosterone |
P30 P90 |
(174) |
| CFA (P1) |
PWT, PWL, paw diameter DRG [ATF3, CGRP, IB4] |
2, 4, 24, 72 h, then 2 × weekly until 8 weeks 12, 24 h, 3, 7, and 14 days |
(175) |
| CFA (P10) |
Paw diameter, PWT SC [IBA1] |
0, 1, 3, 24 h, 7 days 1, 24 h, 7 days |
(165) |
| CAR (P10) |
Paw diameter, PWT SC [IBA1] |
0, 1, 3, 24 h, 7 days 1, 24 h, 7 days |
(165) |
| CAR (P1) |
PWT, PWL, paw diameter DRG [ATF3, CGRP, IB4] |
2, 4, 24, 72 h, then 2 × weekly until 8 weeks 12, 24 h, 3, 7, and 14 days |
(175) |
| CAR (P0, 1, 3, or 14) |
Pain behavior PWL DRG [CGRP, IB4], electrophysiology |
P0, 1, 3, or 14 P56–70 P56 |
(134) |
| CAR (P3 or 12) |
Paw diameter EPM, FST |
0, 0.5, 1, 3, 6, 14, 24, 32, 39, 45, 52, 60, 69 h P50–55 |
(176) |
| CAR (neonate; not specified) |
Electrophysiology (PWT) | P19–23 | (178) |
| CAR (P3) |
PWT | P6, 13, 20, 27, 34, 41, 48, 55, 62 | (135) |
| CAR (P1, 4) |
Fear conditioning PWT, PWL |
P24, 45, 66 P27, 48, 69 |
(177) |
| CAR (P0) |
OFA FST, sucrose preference, stress-induced analgesia test with PWL |
P65–70 P70–90 |
(179) |
| CAR (P0) |
OFA FST, corticosterone |
P60–80 P70–90 |
(210) |
| Formalin (P1–2) |
Formalin test (nociceptive activity) EPM, FST, MWM |
P25 P25–38 |
208) |
| Formalin (P1–3, 1–5, or 10–12) |
Brain histology, WB | P4, 6, 13 | (58) |
| LPS (P14) |
Brain (c-Fos) EPM Fear conditioning PWT |
2.5 h P38–42, 62–68 P60–72 P60–90 |
(181) |
| Zymoson (P10) |
Paw diameter, PWT SC [IBA1] |
0, 1, 3, 24 h, 7 days 1, 24 h, 7 days |
(165) |
| TISSUE-BREAKING PAIN | |||
| Skin Flap (neonate; not specified) |
PWT, electrophysiology | P19–23 or 40–44 | (178) |
| RNP (P0–7) |
Weight gain PWL Alcohol preference, defensive withdrawal, social discrimination, air-puff startle tests |
P8, 15, 21 P16, 22, 65 P20–30 |
(57) |
| RNP (P1–7) |
Fear conditioning PWT, PWL |
P24, 45, 66 P27, 48, 69 |
(177) |
| RNP (P0–14) |
PWL Radial arm water maze Hippocampus [ELISA] |
P28, 56 P56, 57 P70 |
(59) |
| RNP (P0–7) |
PWT OFA MWM OFA, Corticosterone, ACTH, WB |
P8, 15, 22, 43, 57, 85 P25, 87 P24–30, 87–93 P24, 45, 87 |
(187) |
| RNP (P0–7 or 0, 2, 4, 6) |
OFA EPM, FST, Corticosterone |
>P98 >P119 |
(185) |
| RNP (P1–6) |
OFA, EPM, MWM, Rotarod, PWL, Sucrose preference | P60–85 | (62) |
| RNP (P8–14) |
EPM MWM |
P30 P31–33, 34–36, 38 |
(184) |
| Incision (P3, 10, 17) |
PWT, PWL, OFA, brain [c-Fos] | >P90 | (97) |
| Incision (P7 or 28) |
Electrophysiology (PWL) | 0, 1 h | (188) |
| Incision (P3 or 40) |
PWT EMG |
0, 4, 24, 48, 72 h 24 h |
(100) |
| Incision (P3) |
PWT, PWL Electrophysiology |
Weekly, P14–42 P40 |
(144) |
| Incision (P6) |
Development assessment Wire hang test Rotarod OFA, EPM NOR |
P6–21 P17, 18, 20 P17, 19, 21 P18 P19 |
(186) |
| Toe clipping (P7 or 17) |
Developmental assessment OFA, EPM Balance beam Rotarod |
P6–21 P56 P63–65 P70–72 |
(182) |
| Toe clipping (P3 or 7) |
Developmental assessment Grip test, PWL Corticosterone |
1, 3, 5, 12 h, daily for 3 weeks P84–86 P7 |
(183) |
| Tail clip (P8) |
EPM MWM |
P30 P31–33, 34–36, 38 |
(184) |
| NERVE PAIN | |||
| SNI (P10 or 60) |
DRG [IBA1, ATF3, NF200, CGRP, IB4] | 7 days | (191) |
| SNI (P10 or 56) |
PWT PWL SC/DRG [IBA1, NF200, GFAP, IB4], WB |
3, 7, 14, 21, 28, 38, 44 days 3, 7, 14, 21, 35, 51 days 7, 30 days |
(192) |
| SNI (P10 or 33) |
PWT, PWL, Cold pain behavior, Electrophysiology, IC SC [IBA1, BDNF, GFAP] |
1, 7, 14, 21, 28, ±35 days 7, ±21 days |
(211) |
| SNI (P3, 10, 21, 33, or 60) |
PWT | 0, 1, 7, 14, 28 days | (189) |
| CCI (P10 or 60) |
PWT | 0, 7, 14, 28 days | (189) |
| SNI (P14, 28, or 112) |
PWT | 0, 1 days, weekly up to 14 weeks | (190) |
P, post-natal day; CFA, complete Freud's' adjuvant; CAR, carrageenan; RNP; repetitive needle prick; SNI, spared nerve injury; CCI, chronic constriction injury; PWT, paw withdrawal threshold; PWL, paw withdrawal latency; IC, incapacitance meter; SC, spinal cord; DRG, dorsal root ganglion; IBA1, immunostaining for ionized calcium-binding adapter molecule 1 (microglia marker); c-Fos, proto-oncogene; CGRP, calcitonin gene-related peptide; ATF3, Activating transcription factor 3; IB4, isolectin B4; NF200, Neurofilaments protein; GFAP, glial fibrillary acidic protein; BDNF, Brain-derived neurotrophic factor; WB, western blot; ACTH, adrenocorticotropic hormone; EPM, elevated plus maze; OFA, open field arena; MWM, Morris water maze; CPP, conditioned place preference; FST, forced swim test; EMG, electromyography; NOR, novel object recognition.