Table 4.
Rodent models of neonatal pain with subsequent pain and time of assessments.
| “2-Hit” Models | ||||||
|---|---|---|---|---|---|---|
| 1st Stimulus (age) | Basal outcome measure(s) | Age/Time | 2nd Stimulus (age) | Outcome measure(s) | Age/Time | References |
| INFLAMMATORY + INFLAMMATORY PAIN | ||||||
| CFA (P0 or 14) |
Capsaicin (P56–84) | Pain behavior PWT PWL Paw diameter SC [c-Fos] |
5 min 5, 15, 30, 45, 60 min 5, 15, 30, 45 min 60 min |
(195) | ||
| CFA (P1 or 14) |
CFA (P84) | PWL | P85 | (193) | ||
| CFA (PO) |
PWT, PWL | P56 | CFA (P56) | PWT, PWL | P57 | (194) |
| CFA (P0, 1, 3, or 14) |
PWL | P56–70 | CFA (P56–70) | PWL | 24 h | (134) |
| CFA (P0, 1, 3, or 14) |
PWL | P56–70 | Formalin (P56–70) | Pain behavior | Every 5 min for 60 min | (134) |
| CAR (P0, 1, 3, 5, 8, 10, 12, or 14) |
PWT, PWL | P40 | CFA (P40) | PWT, PWL | P41 | (135) |
| CAR (P3) |
CFA (P6, 13, 24, 40, or 62) | PWT | 24 h | (135) | ||
| CAR (P3) |
PWT, PWL | P120–125 | CFA (P120–125) | PWT, PWL | 24 h | (135) |
| CAR (P0 or P14) |
PWL, Pain behavior | 3, 6, 12, 18, 24, 48, 60 h, and P60 | CFA (P61) | PWT, PWL, paw diameter | P62 | (198) |
| CAR (P0) |
PWL, tail flick | P40, 60 | CFA (P60) | PWL, paw diameter | 1, 7, 14, 21 | (196) |
| CAR (P0, 8, or 14) |
PWL, paw diameter | P40, 60 | CFA (P60) | PWL | P61 | (197) |
| CAR (P3) |
PWL | P48, 49 | CFA (P50) | PWL, tail flick, electrophysiology | 24 h | (145) |
| CAR (P3 or 14) |
Mustard oil (Colon) (P60–70) | PWL, visceromotor response | 0, 30, 90, 150, 210 min | (199) | ||
| Formalin (P1–2 or 7–8) |
PWL | P25 | Picric acid + maternal deprivation (P25) | Pain behavior PWL | 1–20 min P26 | (96) |
| Formalin (P7–8) |
Formalin (P25) | EPM, FST, MWM, nociceptive activity | P25–38 | (200) | ||
| INFLAMMATORY PAIN + STRESS | ||||||
| CAR (P0) |
Chronic stress (P82–109) | MWM | P94–117, 144–162, 424–442 | (61) | ||
| CAR (PO) |
Chronic stress (P85–P105) | FST | 7 days | (210) | ||
| INFLAMMATORY + TISSUE-BREAKING PAIN | ||||||
| CFA (P1) |
PWT | P35, 42, 49 | Incision (P50) | PWT | 4 h, 1, 2, 3, 4, 7 d | (171) |
| INFLAMMATORY + NERVE INJURY | ||||||
| CFA (P0, 1, 3, or 14) |
Sciatic nerve injection (P56–84) | SC [WGA-HRP density] | 48 h | (134) | ||
| CFA (PO) |
PWT, PWL | P56 | SNL (P56) | PWT, PWL | P57, 60, 63, 70, 77, 84 | (194) |
| CFA (tail) (P3) |
PWT, PWL | P56 | TNI (P56) | PWT, PWL | P57, 60, 63, 70, 77, 84 | (194) |
| SNI (P10) |
SC [IBA1] | 6, 24, 72 h | LPS (P10–19, 19–21) | PWT | 0, 30, 60, 90, 120, 150 min | (201) |
| TISSUE-BREAKING + INFLAMMATION/OTHER PAIN | ||||||
| RNP (P0–7) |
CFA (P56) | PWT | P57 | (202) | ||
| RNP (P2–8) |
PWL | P14–16, 35–36, 64–66 | Formalin (P14–16, 35–37, or 64–66) | Pain behavior | 2–7 days | (203) |
| TISSUE-BREAKING + TISSUE-BREAKING PAIN | ||||||
| RNP (P0–7) |
PWT PWL |
1, 3, 5 h (P0–7), Weekly, P21–56 Weekly, P21–56 |
Incision (P56) | PWT SC [CGRP, VGLUT2] |
1, 3, 4, 7, 9, 11 days | (37) |
| RNP (P0–7) |
PWT | 1, 3, 5 h (P0–7) | Incision (P42–56) | Electrophysiology | P42–56 | (98) |
| RNP (P0–7) |
PWT | 1, 3, 5 h (P0–7), Weekly P21–56 | Incision (P56) | PWT | 1, 3, 5, 7, 9 days | (204) |
| RNP (P0–7) |
PWT PWT, PWL |
1, 3, 5 h (P0–7) Weekly P21–56 | Incision (P56) | PWT, PWL | 1, 3, 5, 7, 9 days | (214) |
| RNP (P2–14) |
Acute stress (P15 or 20–21) | ACTH, corticosterone | 5, 30, 60, or 90 min | (205) | ||
| Incision (P3, 6, 10, 21 or 40) |
PWT | 0, 4, 24, 48, 72 h | Incision (P17, 20, 24, 35, or 54) | PWT EMG |
0, 4, 24, 48, 72 h, and 7 days 24 h |
(100) |
| Incision (P3) |
Incision (P56) | PWT, PWL, IBA1, EMG | 0, 1, 3, 5, 7, 10, 14, 19, 21, 28 days | (16) | ||
| Incision (P3, 10, 17) |
Incision (P90) | PWT, PWL, OFA, brain [c-Fos], novelty-induced hyponeophagia | 0, 1, 2, 5 days | (97) | ||
| Incision (P3) |
PWT | 3, 4, 24 h | Incision (P42–49) | PWT, PWL EMG CPP, NOR |
0, 1, 2, 4, 7, 9, 12, 17, 21 days 0, 24 h 24 h |
(207) |
| Incision (P3) |
PWT EMG SC [IBA1] |
3, 4, 24, 48, 72 h 6 h 24 h |
Incision (P42) | PWT, PWL EMG, OFA SC [IBA1] |
0, 1, 2, 3, 7, 10, 14, 17, 21 days 24 h P6 |
(206) |
| Incision (P3) |
Incision (P70) | PWT, PWL, inclined plate test SC [IBA1] Electrophysiology |
0, 1, 3, 5, 7, 14, 21 days 0, 1, 3, 5 7 days 7 days |
(163) | ||
| OTHER PAIN + OTHER PAIN | ||||||
| Orogastric suctioning (P2–11) |
PWL | P60 | Colorectal distention (P60) | PWL, visceral sensitivity | 24 h | (209) |
| Lesion to motor cortex (P7) |
Lesion to motor cortex (P70) | SC histology | P70 | (208) | ||
| Electrical stimulation (P10) |
Electrical stimulation ± Capsaicin (adult; not specified) | PWT SC [IBA1] |
0, 3, 24, 48 h 48 h |
(164) | ||
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.