title: Enhancement of Antihyperalgesia by the Coadministration of N-palmitoylethanolamide and Acetaminophen in Diabetic Rats.
abstract: Preclinical Research 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.
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., 11340, México.
authors.forename: Myrna
authors.initials: M
authors.lastname: Déciga-Campos
authors.affiliation: Facultad de Química, Universidad Autónoma de Yucatán, Mérida, Yucatán, 97150, México.
authors.forename: Rolffy
authors.initials: R
authors.lastname: Ortíz-Andrade
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000627:therapeutic use; D000577:Amides; D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D010169:Palmitic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D013311:Streptozocin; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000700:Analgesics; D004983:Ethanolamines; D010169:Palmitic Acids; D000082:Acetaminophen; D013311:Streptozocin; C005958:palmidrol
keywords: N-palmitoylethanolamide; acetaminophen; antihyperalgesia; diabetic neuropathy; synergism