Figure 9
Tactile (A) and thermal (B) sensory testing data for diabetic mice receiving either intranasal or intraperitoneal nabilone at low, medium, or high dose, with comparison to non-diabetic mice and saline delivery is shown. Those diabetic mice receiving medium or high doses of intranasal or intraperitoneal nabilone had amelioration of both tactile allodynia and thermal hyperalgesia beginning at week 7 when nociceptive behaviors began. This protection against the development of the neuropathic pain state disappeared after discontinuation of nabilone at week 14. Tactile (C) and thermal (D) sensory testing data for mice with diabetes receiving either intranasal or intraperitoneal WIN55212-2 at low, medium, or high dose, with comparison to non-diabetic mice receiving intranasal or intraperitoneal saline is also demonstrated. Those diabetic mice receiving high doses of intranasal or intraperitoneal WIN55212-2 had amelioration of tactile allodynia beginning at week 7 when nociceptive behaviors began, while thermal hyperalgesia was modulated by either medium or high doses of intranasal or intraperitoneal WIN55212-2. This protection against the development of the neuropathic pain state disappeared after discontinuation of nabilone at week 14, after which all diabetic mouse cohorts had comparable levels of tactile allodynia and thermal hyperalgesia. For both tactile (A, C) and thermal (B, D) testing, significant differences were detected between the diabetic mouse group receiving medium (γ) or high doses (θ) of intranasal nabilone/WIN55212-2 or medium (φ) high (Ψ) doses of intraperiteonal nabilone/WIN55212-2 when compared to the diabetic mouse group receiving low dose intranasal or intraperitoneal nabilone/WIN55212-2 respectively (non-matched ANOVA tests, F-values range between 0.76-3.07 for indicated groups and time points, n ≥ 4, p < 0.05). Area under the curve (AUC) measurements were also significantly different in each case (p < 0.05) for weeks 1-13, but not for assessment of tactile allodynia in mice receiving any dose/route for WIN55212-2 (C). [n = 4-10 mice in each mouse cohort for each time point]