Table 1.
List of included studies.
| Reference | Study Design § | Strain/Stock | Age/Weight | Sex | Type of Intervention | Intervention (Model Created or Procedure Investigated) | Pain Classification Assigned | Intervention Effect on MGS Score * |
|---|---|---|---|---|---|---|---|---|
| Akintola et al., 2017 [30] | RCT | C57BL/6 | 10–12 weeks | M | Animal Model | Chronic constriction injury model for pain | Neuropathic | ↑ |
| Bu et al., 2015 [31] | RCT | BALB/c | 6–8 weeks | F | Animal Model | Chronic pelvic pain | Visceral | ↑ |
| Burgos-Vega et al., 2019 [32] | RCT | ICR | 6–8 weeks | M,F | Animal Model | Migraine | Neuropathic | ↑ |
| Chartier et al., 2020 [26] | RCT | C57BL/ 6JArc | 8 weeks | F | Animal Model | Colitis-associated colorectal cancer | Visceral | Nil |
| Cho et al., 2019 [33] | RCT | CD-1, C57BL/6N | 7–9 weeks | M,F | Animal Model | Craniotomy with different analgesics | Neuropathic | ↑ (reduced by analgesics) |
| de Almeida et al., 2019 [34] | Pre-test, post-test | BALB/c | 20–30 g | F | Animal Model | Cancer-induced nociception | Mixed | ↑ |
| de Almeida et al., 2020 [35] | RCT | BALB/c | F | Animal Model | Cancer-induced nociception | Mixed | ↑ | |
| Duffy et al., 2016 [36] | RCT | C57BL/6J | 10–12 weeks | F | Animal Model | Experimental autoimmune encephalomyelitis (EAE) | Neuropathic | ↑ |
| Dwivedi et al., 2016 [27] | RCT | Transgenic (BL/6 background) PCSK9 KO mice and PCSK9 overexpression | 10–12 weeks | M,F | Animal Model | Caecal Ligation and Puncture model of sepsis | Visceral | ↑ |
| Faller et al., 2015 [37] | RCT | C57BL/6J, transgenic overexpressing creatine transporter in the heart (BL/6 background) | 12–16 weeks | F | Animal Model | Myocardial infarction created through thoracotomy | Visceral | ↑ (reduced by analgesics) |
| Gallo et al., 2020 [38] | RCT (factorial) | Crl:CD1(ICR) | 8–9 weeks | M | Husbandry/Procedural | Carotid artery catheterisation | Acute | ↑ |
| Guo et al., 2019 [39] | RCT | C57BL/6 | 9 weeks | M,F | Animal Model | Orofacial pain | Acute | |
| Hassan et al., 2017 [28] | RCT | C57BL/6N, PYY knockout | 10 weeks | M | Animal Model | Colonic nociception | Visceral | ↑ |
| Hassler et al., 2019 [40] | RCT | ICR, C57BL/6J, and PAR2 (BL/6 background) | 20–30 g | M | Animal Model | Migraine | Neuropathic | ↑ |
| Herrera et al., 2018 [41] | RCT | CD-1 | 18–20 g | nr | Animal Model | Bothops Asper venom | Visceral | ↑ |
| Hohlbaum et al., 2017 [42] | RCT | C57BL/6JRj | 11–13 weeks | M, F | Husbandry/Procedural | Isoflurane anaesthesia | None/momentary | ↑ (female mice only) |
| Hohlbaum et al., 2018 [43] | RCT | C57BL/6JRj | 11–13 weeks | M, F | Husbandry/Procedural | Ketamine/xylazine anaesthesia | None/momentary | ↑ |
| Hohlbaum et al., 2020 [44] ⁋ | Quasi-experimental | C57BL/6JRj | 11–13 weeks | M, F | Biological | Ketamine /xylazine anaesthesia | N/A | Study investigated inter-observer reliability in scoring |
| Hsi et al., 2020 [45] | RCT | C57BL/6N | 7–9 weeks | F | Animal Model | Animals with hypoglycaemia following Roux-en-Y Gastric Bypass surgery | None/momentary (outcome of interest is the hypoglycaemia) | Nil ǂ |
| Jirkof et al., 2020 [46] | RCT | C57BL/6J | F | Husbandry/Procedural | Tramadol treatment effect on MGS between laboratories | None/momentary | Nil | |
| Jurik et al., 2014 [47] | RCT | TRPV1 knock-out (BL/6 background) | 8–16 weeks | M | Animal Model | Abdominal constriction test and acute pancreatitis as models of pain. Effects of knockout versus wildtype genotype | Visceral | No effect of genotype on MGS scores |
| Kim et al., 2015 [48] | RCT | ICR | M,F | Animal Model | Hyperalgesic priming via IL-6 and Carrageenan injection | Acute | ↑ | |
| Langford et al., 2010 [20] | RCT | CD-1 (ICR:Crl) | 6–18 weeks | M,F | Animal Model | 14 models of pain | Acute | ↑ |
| Leach et al., 2012 [49] | RCT | CD-1 | M | Husbandry/Procedural | Vasectomy surgery | Acute | ↑ (reduced by analgesics) | |
| Mai et al., 2018 [50] | RCT | C57BL/6J | 8–12 weeks | M | Animal Model | Caecal ligation and puncture model of sepsis | Visceral | ↑ |
| Matsumiya et al., 2012 [51] | RCT | CD1 (ICR:Crl) | 6–8 weeks | M,F | Husbandry/Procedural | Ventral ovariectomy and response to analgesics | Acute | ↑(reduced by analgesics) |
| Meyer et al., 2020 [52] | RCT | C57BL/6J | 10–12 weeks | M | Husbandry/Procedural | Common recovery blood sampling routes (facial vein, retrobulbar, tail vein with anaesthetic and handling control) | None/momentary | ↑—anaesthetic, facial vein bleeding, or retrobulbar compared to handling |
| Miller et al., 2015 [53] | Pre-test, post-test | CBA, DBA/2 | M | Husbandry/Procedural | Isoflurane anaesthesia and buprenorphine analgesic | None/momentary | Nil (↑ by isoflurane in DBA/2 strain) | |
| Miller and Leach, 2015a [54] | RCT | C57BL/6, C3H/He, CD-1 BALB/c | 8 weeks | M,F | Biological | Impact of sex, strain, time of day or habituation | None/momentary | Nil-order ↑- males compared to females (but strain dependant and not always consistent) Strain effects present Time of day effects with sex and strain differences |
| Miller and Leach, 2015b [55] | RCT | C57BL/6 | 8 weeks | M | Husbandry/Procedural | Ear notching and analgesic effects | None/momentary | Nil |
| Miller et al., 2016 [56] | Pre-test, post-test | CBA | 25.6–28.7 g | M | Husbandry/Procedural | Vasectomy surgery | Acute | ↑ |
| Miller and Leach, 2016 [57] | RCT | CBA, DBA/2 | M | Husbandry/Procedural | Handling method: tail versus tube | None/momentary | Nil | |
| Mitchell et al., 2020 [58] | RCT | ArcCrl:CD | 12 weeks | F | Animal Model | TNBS-induced Crohn’s-like colitis | Visceral | ↑ |
| Mittal et al., 2016 [59] | RCT | Transgenic HbSS-BERK (with relevant controls) | M,F | Animal Model | Sickle cell disease and effects of cold | Acute | ↑—in females, cold also had impact | |
| Rea et al., 2018 [60] | RCT | C57BL/6J, CD1 | 10–14 weeks | M,F | Animal Model | Pain as result of migraine | Neuropathic | ↑ |
| Rosen et al., 2017 [61] | RCT | CD-1 (Crl:ICR), Nude (Crl:CD1- Foxn1nu), C57BL/6J, C57BL/6-Rag1 tm1Mom/J, mutant mice lacking expression of the Oprd1 (-opioid receptor) gene | 7–12 weeks | M,F | Animal Model | Pregnancy analgesia after inflammatory insult induced by administration of complete Freund’s adjuvant (CFA) | Visceral (pregnancy state). | ↑—in late-pregnant mice compared to nulliparous females |
| Rossi et al., 2020 [62] | RCT | Mixed CD-1 and C57BL/6J background | 17–21 weeks | M,F | Animal Model | Tooth pulp injury | Acute | ↑ |
| Roughan et al., 2016 [63] | RCT | BALB/c | 25–30 g | M | Husbandry/Procedural | Handling method: tail versus cupping at time of surgery | None/momentary | Nil (although surgery itself increased MGS) |
| Roughan and Sevenoaks, 2019 [64] | RCT | BALB/cAnNCrl | 10–13 weeks | M,F | Husbandry/Procedural | Ear tattooing and tagging, with tail handling method or tunnel | None/momentary | ↑ tail versus tunnel ↑ males versus females ↑ ear tagging versus tattoo |
| Sorge et al., 2014 [65] | RCT | CD-1 (ICR:Crl), C57BL/6J | 6–12 weeks | M,F | Husbandry/Procedural | Effect of gender/gender-specific and other animal pheromones on response to nociceptive assays | None/momentary (intervention of interest is the pheromones) | ↓ with male observer or male’s T-shirt compared to no observer |
| Serizawa et al., 2019 [18] | RCT | C57BL/6J | 7 weeks | F | Animal Model | Experimental autoimmune encephalomyelitis (EAE) | Neuropathic | ↑ |
| Tillu et al., 2015 [66] | RCT | ICR, C57BL/6 | 20–25 g | M | Animal Model | Hyperalgesic priming | Acute | ↑ |
| Tuttle et al., 2018 [67] | RCT | CD-1 (ICR:Crl) | 6–12 weeks | M,F | Husbandry/Procedural | Ventral ovariectomy and response to analgesics, xymogen assay (validation of automated scoring) | Acute | ↑ (reduced by analgesic) |
| Wang et al., 2017 [68] | RCT | C57BL/6, TRPV1 KO | 8–12 weeks | M | Animal Model | Masseter inflammation | Acute | ↑ |
| Wang et al., 2018 [69] | RCT | C57BL/6, TRPV1 KO (C57BL/6 background), TRPA1 KO (mixed B6; 129 background) | 8–12 weeks | M | Animal Model | Masseter inflammation | Acute | ↑ |
| Wang et al., 2019 [70] | RCT | C57BL/6 | 12 weeks | M | Animal Model | Orthodontic tooth movement | Acute | ↑ |
| Wu et al., 2016 [71] | RCT | C57BL/6 | 8–19 weeks | M | Animal Model | Spinal cord injury | Neuropathic | ↑ |
| Zhu et al., 2017 [72] | RCT | BALB/c | 25–30 g | M | Animal Model | Orthodontic tooth movement | Acute | ↑ |
§ The terminology randomised control trial (RCT) has been used to indicate use of a comparator with a parallel arrangement of study groups; however, randomisation was not necessarily performed at all or to a high standard in all studies. This was not specifically investigated as part of this review. * General consistent direction of effect ǂ no sham control so effect of model unknown ⁋ Study used photos obtained from Hohlbaum 2017 [42] study. In reporting, we have not considered this to represent an additional animal study for presentation of animal-focussed data.