t. AM1241. Compared to non-neuropathic control rats, neuropathic rats showed a robust ipsilateral

(ANOVA, F(1,8) = 34.19; P = 0.0004) and contralateral (ANOVA, F(1,8) = 27.51; P = 0.0008) increase in dorsal horn MAGL IR (Fig. 6A and 6B). In contrast, spinal tissue collected from rats given an i.t. AM1241 injection revealed significantly lower bilateral MAGL IR (ipsilateral ANOVA, F(1,8) = 8.356; P = 0.0202; contralateral ANOVA, F(1,8) = 4.146; P = 0.0761, respectively) (Fig. 6A and 6B). Interestingly, no interpretable #Volasertib datasheet keyword# or meaningful change in FAAH IR between non-neuropathic and neuropathic CCI rats was observed following surgical manipulation (ipsilateral ANOVA, F(1,8) = 8.072; P = 0.0218; contralateral ANOVA, F(1,8) = 0.09666; P = 0.7638), or following i.t. AM1241 or vehicle treatment (ANOVA, F(1,8) = 0.5436; P = 0.4820 and ANOVA, F(1,8) = 2.174; P = 0.1786, respectively) Inhibitors,research,lifescience,medical (Fig. 6C and 6D). Figure 6 Immunofluorescent intensity quantification of the spinal cord dorsal horn reveals that AM1241 reduces the expression of the endocannabinoid degradative enzyme, MAGL but does not alter FAAH. (A, B) Compared to control rats, MAGL IR expression was increased … DRG Immunohistochemical Inhibitors,research,lifescience,medical analysis: GFAP, IL-1β, p-p38MAPK,

and IL-10 Immunohistochemical detection of GFAP, IL-1β, p-p38MAPK, and anti-inflammatory IL-10 in L4–L5 DRG that correspond to the ipsilateral and contralateral spinal cord segments was quantified. Results revealed that compared to non-neuropathic control rats, CCI-induced neuropathic rats displayed a robust bilateral increase in GFAP IR in DRG (ipsilateral ANOVA, F(1,8) Inhibitors,research,lifescience,medical = 9.133; P = 0.0165; contralateral ANOVA, F(1,8) = 8.443; P = 0.0197,

respectively) (Fig. 7A and 7B). However, i.t. AM1241 injection robustly blocked bilateral increases in GFAP IR (ipsilateral ANOVA, F(1,8) = 27.19; P = 0.0008; contralateral ANOVA, F(1,8) = 5.223; P = 0.0516, respectively) (Fig. 7A and 7B). Intriguingly, DRG changes in levels of p-p38MAPK IR occurred in the ipsilateral (ANOVA, F(1,8) = 6.885; P = 0.0305), but not the contralateral DRG (ANOVA, F(1,8) Inhibitors,research,lifescience,medical = 0.2013; P = 0.6656) to the sciatic nerve damage (Fig. 7C and 7D), and i.t. AM1241 tuclazepam injection revealed ipsilateral p-p38MAPK IR that was similar to controls (ANOVA, F(1,8) = 15.92; P = 0.0040). No change in p38MAPK IR was detected in the contralateral DRG (ANOVA, F(1,8) = 2.051; P = 0.1900). This unilateral change was also observed with IL-1β IR due to CCI surgery (ipsilateral ANOVA, F(1,8) = 6.414; P = 0.0351; contralateral ANOVA, F(1,8) = 0.3111; P = 0.5923), and AM1241 treatment resulted in levels similar to controls (ipsilateral ANOVA, F(1,8) = 52.03; P < 0.0001; contralateral ANOVA, F(1,8) = 0.2221; P = 0.6500) (Fig. 7E and 7F). An intriguing unilateral decrease in IL-10 IR was measured in CCI neuropathic rats only (ipsilateral ANOVA, F(1,8) = 17.42; P = 0.0031; contralateral ANOVA, F(1,8) = 1.583; P = 0.2438), while an i.