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Multiple comparisons after analysis of variance were performed using a Tukey��s test. For H/R results (Fig?2), all data were compared first by 2-way analysis of variance for between-group comparisons over time and multiple comparisons after analysis using Tukey��s post hoc testing. For within-group comparisons over time, all data were compared using one-way anova and multiple comparisons after analysis were completed using Tukey��s post hoc testing. For all data, P? http://www.selleckchem.com/products/abt-199.html (Version 5.04; GraphPad, San Diego, CA, USA). HbSS-BERK mice, whose phenotype is the most severe for sickling and vaso-occulsion, exhibited the greatest degree of hyperalgesia on all nociceptive measures tested. The magnitude of hyperalgesia http://www.selleck.cn/products/CP-690550.html in these mice increased with age. Deep hyperalgesia (measured by decreased grip force) occurred early in life, even with modest sickle haemoglobin levels in NY1DD and S+SAntilles mice (Fig?1C), which did not exhibit mechanical or heat sensitivity (Fig?1A, B and F). S+SAntilles mice were particularly sensitive to cold and this increased with age (Fig?1D and E). NY1DD and S+SAntilles were less sensitive to heat and mechanical stimuli than HbSS-BERK mice. Thus, different strains of mice with varying severity exhibit different degrees of hyperalgesia to various sensory modalities. Grip force appears to be the most sensitive measure for detecting hyperalgesia in all of the genetic strains used, however, HbSS-BERK mice displayed the greatest degree of hyperalgesia across all pain tests. It is well known that mice exhibit strain-dependent sensitivities in behavioural measures of nociception (Mogil et?al, 1999). As the transgenic sickle mice used in this study were obtained from two different strains of mice (C57/BL6 for NY1DD http://www.selleckchem.com/products/ABT-263.html and S+SAntilles and HbAA-BERK for HbSS-BERK), we compared behavioural measures of pain in these different strains of control mice to determine if enhanced sensitivity to any of the pain measures observed in the sickle mice could be attributed to differences in sensitivity of the background controls or to the sickle phenotype. As shown in Fig?2, C57/BL6 mice exhibited a decrease in paw withdrawal threshold to mechanical stimuli and a decrease in paw withdrawal latency to heat as compared to the HbAA-BERK control mice. Although we do not believe that the increased sensitivity of sickle mice is due to strain differences (due to the reasons described below), these results underscore the need to compare background strains of mice so that behavioural measures of pain can be carefully interpreted.