Fig 1.
Flow diagram of included studies.
CIPN, chemotherapy-induced peripheral neuropathy.
Fig 2.
Description and summary of data sets included in this review.
Table 1.
Pain-related behavioural outcome measures across intervention and modelling experiments.
Numbers indicate the number of individual comparisons.
Table 2.
Other behavioural outcome measures across intervention and modelling experiments.
Number of individual comparisons.
Table 3.
Reporting of measures to reduce the risk of bias and reporting.
Fig 3.
Impact of study design in modelling experiments using pain-related behavioural outcomes (data set 1a).
The size of the squares represents the number of nested comparisons that contribute to that data point and the value N represents the number of animals that contribute to that data point. (A) Outcome measure accounted for a significant proportion of the heterogeneity. ETW, ELW, and complex behaviours used to measure pain. (B) Chemotherapeutic agent accounted for a significant proportion of the heterogeneity. ELW, evoked limb withdrawal; ETW, evoked tail withdrawal; SMD, standardised mean difference.
Table 4.
Model details including chemotherapeutic agents, route of administration, median cumulative dose, and upper and lower quartiles (data set 1a).
Fig 4.
Impact of study design in modelling experiments using pain-related behavioural outcomes (data set 1a).
The size of the squares represents the number of nested comparisons that contribute to that data point, and the value N represents the number of animals that contribute to that data point. (A) Sex accounted for a significant proportion of the heterogeneity. (B) Strain accounted for a significant proportion of the heterogeneity. SMD, standardised mean difference.
Fig 5.
Power analysis for modelling experiments (data set 1a).
Number of animals required per group to obtain 80% power with a significance level of 0.05 using mechanical monofilaments, Randall-Selitto paw pressure test, electronic ‘von Frey’, acetone test/ethyl chloride spray, cold plate, and Hargreave’s. Effect sizes calculated by SMD. SMD, standardised mean difference.
Fig 6.
Effect sizes associated with measures to reduce risk of bias in modelling experiments using pain-related behavioural outcomes (data set 1a).
Fig 7.
Effect sizes associated with reporting of compliance with animal welfare regulations and a statement of potential conflict of interests in modelling experiments using pain-related behavioural outcomes (data set 1a).
Fig 8.
Assessment of publication bias in modelling experiments in which a pain-related outcome was used (data set 1a).
(A) Visual inspection of the funnel plot suggests asymmetry. Filled circles represent reported experiments. Solid line represents global effect size, and dashed line represents adjusted global effect size. (B) Trim and fill analysis imputed theoretical missing studies (unfilled circles). Filled circles represent reported experiments. Solid line represents global effect size, and dashed line represents adjusted global effect size. (C) Egger’s regression indicated small study effects.
Fig 9.
Intervention accounted for a significant proportion of the heterogeneity in intervention experiments using pain-related behavioural outcomes (data set 2a).
Plot shows interventions with 10 or more comparisons. The size of the squares represents the number of nested comparisons that contribute to that data point, and the value N represents the number of animals that contribute to that data point.
Fig 10.
Impact of study design in intervention experiments using pain-related behavioural outcomes (data set 2a).
The size of the squares represents the number of nested comparisons that contribute to that data point, and the value N represents the number of animals that contribute to that data point. (A) Outcome measure accounted for a significant proportion of the heterogeneity. (B) Chemotherapeutic agent accounted for a significant proportion of the heterogeneity. (C) Time of assessment accounted for a significant proportion of the heterogeneity. (D) Strain accounted for a significant proportion of the heterogeneity.
Fig 11.
Rank order of clinical and preclinical drugs (data set 2a).
A Spearman’s correlation was run to assess the relationship between clinical and preclinical rank of 17 drugs. There was no correlation between clinical and preclinical rank; rs = −0.0099, p = 0.9699.
Fig 12.
Power analysis for intervention experiments.
Number of animals required to obtain 80% power with a significance level of 0.05 using mechanical monofilaments, Randall-Selitto paw pressure test, electronic ‘von Frey’, acetone test/ethyl chloride spray, cold plate, and Hargreave’s (data set 2a). Effect sizes calculated by SMD. SMD, standardised mean difference.
Fig 13.
Effect sizes associated with measures to reduce risk of bias in intervention experiments using pain-related behavioural outcomes (data set 2a).
Fig 14.
Effect sizes associated with reporting of compliance with animal welfare regulations and a statement of potential conflict of interests in intervention experiments using pain-related behavioural outcomes (data set 2a).
Fig 15.
Intervention experiments in which a pain-related outcome was used (data set 2a).
(A) Visual inspection of the funnel plot suggests asymmetry. Filled circles represent reported experiments. Solid line represents global effect size, and dashed line represents adjusted global effect size. (B) Trim and fill analysis imputed theoretical missing studies (unfilled circles). Filled circles represent reported experiments. Solid line represents global effect size, and dashed line represents adjusted global effect size. (C) Egger’s regression indicated small study effects. vN, square root of N.
Table 5.
Publication level data abstracted from each publication.
Table 6.
Experiment level data abstracted from each publication.