AM1714 normalized paclitaxel induced mechanical allodynia in accordance with pre paclitaxel standard thresholds. The high dose, but not the center or low dose of AM1714 Cathepsin Inhibitor 1 elevated paw withdrawal thresholds relative to day 21 pre treatment thresholds. Medicinal Specificity Neither the CB1 selective antagonist SR141716 nor the CB2 selective antagonist SR144528 improved paclitaxel evoked mechanical allodynia in accordance with pre shot thresholds. The CB2 antagonist SR144528 blocked the anti allodynic effects of both AM1241 and AM1714. Paw withdrawal thresholds in agonist groups pretreated with SR144528 did not vary from the car condition. Post hoc comparisons failed to reveal any differences in the effects induced by both AM1714 or AM1241. SR141716 failed to prevent the anti allodynic effects produced by both AM1241 or AM1714. Cellular differentiation Paw withdrawal thresholds in paclitaxel addressed groups receiving DMSO were less than those observed in groups receiving the CB2 agonists in either the presence or absence of the CB1 antagonist. Paw withdrawal thresholds were similar in groups pre-treated with SR141716 to those observed in groups receiving either agonist alone. However, animals receiving SR141716 prior to AM1714 demonstrated raised paw withdrawal thresholds relative to baseline pre paclitaxel thresholds. Post drug injection foot withdrawal thresholds were higher in most groups relative to day 21 pre injection thresholds with the exception of vehicle. Ramifications of Morphine on Paclitaxel evoked Mechanical Allodynia The high dose of morphine suppressed paclitaxel induced mechanical allodynia relative to the vehicle situation Lapatinib clinical trial and normalized foot withdrawal thresholds relative to pre paclitaxel baseline thresholds. The lower dose of morphine failed to modify article paclitaxel paw withdrawal thresholds. Debate Two structurally distinct CB2 agonists attenuated technical allodynia induced by treatment with the chemotherapeutic agent paclitaxel. Animals receiving paclitaxel remained in relatively good health as evidenced by the observation of normal weight gain during the span of chemotherapy treatment. But, one fatality was observed after two treatments of paclitaxel. Paclitaxel evoked technical hyper-sensitivity can’t be caused by sensitization to repeated testing, foot withdrawal thresholds were firm in animals receiving the cremophor: ethanol: saline vehicle instead of paclitaxel within the same time course. Technical allodynia was observed in paclitaxel addressed animals examined weekly as much as 3 months following the initiation of chemotherapy treatment in a pilot study. Paw withdrawal thresholds were similarly reduced in accordance with baseline from day 14 to 72 post paclitaxel in this study, therefore day 21 was selected for the analysis of drug effects on paclitaxel evoked mechanical allodynia.