Enhancement of Antihyperalgesia by the Coadministration of N‐palmitoylethanolamide and Acetaminophen in Diabetic Rats

The objective of this study was to evaluate the pharmacological antihyperalgesic interaction between N‐palmitoylethanolamide (PEA) and acetaminophen in diabetic rats using the formalin paw test. Streptozotocin (STZ)‐induced diabetic rats received subcutaneous injections in the paw of PEA alone (1–100 μg/paw) or acetaminophen alone (3–300 μg/paw) 15 min before formalin (0.5%) injection. The results revealed concentration‐dependent responses produced by PEA (EC50 = 7.19 ± 0.7 μg/paw) and acetaminophen (EC50 = 57.9 ± 1.9 μg/paw). Isobolographic analysis was used to evaluate the pharmacological interaction between the PEA + acetaminophen using the EC50 value and a fixed 1:1 ratio combination. The isobologram demonstrated that the combination investigated in this study produced a synergistic interaction; the experimental value (EC50= 23.64 ± 1.9 μg/paw) was significantly smaller than those that resulted from theoretical calculations (EC50 = 32.56 μg/paw). These results provide evidence that PEA in combination with acetaminophen could be useful for pain therapy in neuropathic diabetic patients. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.
Source: Drug Development Research - Category: Drugs & Pharmacology Authors: Tags: Research Article Source Type: research