Zinnia grandiflora (Asteraceae) is used to alleviate several painful disorders. The effects of an essential oil prepared by hydrodistillation from Z. grandiflora (EOZ) and its major compound on neuropathic pain, allodynia, and inflammation in mice were assessed. Headspace-solid phase microextraction analysis of an aqueous extract was also carried out. GC-MS analyses of all volatiles revealed that germacrene D (13.24%) and desmethylisoencecalin (DME) (13.24%) were the most abundant compounds. EOZ was effective in reducing inflammation and allodynia in mice. EOZ (300 mg/paw) reverted tactile allodynia more effectively than gabapentin (100 μg/paw). DME (0.1â10 µg/paw) responses in the carrageenan model were concentration-dependent; the maximum effect was observed at 10 µg/paw, like that of diclofenac (30 μg/paw). In the spinal nerve ligation model, DME (0.1â10 μg/paw) exerted a concentration-dependent anti-allodynic action; its effect was better than that of gabapentin. A method to quantify zinagrandinolide E in the crude drug was developed and validated.