Intraspinal injection of quisqualic acid (QUIS) is associated with the development of spontaneous excessive grooming behavior in male Sprague Dawley rats. To further characterize this pain-like behavior we evaluated the relationship between the onset of this behavior and the rostrocaudal spread of injury-induced neuronal loss in 3 different strains of male rats. The severity and progression of this behavior also were evaluated. Unilateral intraspinal injections of 125 mmol/L QUIS were made in the following groups: Sprague Dawley males (SDMs, n = 21); Long Evans males (LEMs, n = 17); and Wistar Furth males (WFMs, n = 11). Because of differences in grooming characteristics between male and female rats, the modulatory effects of female gonadal hormones also were evaluated in Sprague Dawley females (SDFs, n = 17); bilaterally ovariectomized Sprague Dawley females (OVXs, n = 11); and SDMs treated with either 17-beta-estradiol (50 microg/kg; SDM-Est, n = 9) or progesterone (5 mg/kg; SDM-Pro, n = 11). The results showed that the development of excessive grooming behavior in males of all strains and ovariectomized females is related to the rostrocaudal spread of a specific pattern of neuronal loss in the dorsal horn. Excessive grooming behavior in SDFs was similar in many respects to that found in SDMs; however, SDFs did not show a dependence on the longitudinal extent of injury for the onset of this behavior. The onset, severity, and progression of excessive grooming in OVX females were similar to that found in SDMs. Furthermore, 8 of 9 estradiol-treated SDMs developed severe grooming characterized by an early onset and progressive time course, whereas progesterone treatment delayed the onset of grooming and attenuated its severity and progression. Strain-related differences in some, but not all, grooming characteristics also were observed, eg, WFMs exhibited more aggressive grooming than SDMs or LEMs. In conclusion, the results showed gender, strain, and gonadal hormones influence the onset and progression of injury-induced excessive grooming behavior. A causal relationship also was found between the onset of this behavior and the longitudinal extent of injury.