Aims: We studied the roles of cutaneous and spinal TRPA1 channels in maintenance of mechanical hyperalgesia induced by diabetes mellitus or neurogenic inflammation in the rat. Methods: Diabetes was induced by streptozotocin. Neurogenic inflammation of the skin was induced in non-diabetic animals by topical application of 50% mustard oil, a TRPA1 channel agonist, on a 2 sq.cm area of the plantar skin. Hyperalgesia was assessed by the monofilament- and paw pressure- induced limb withdrawal response. Chembridge- 5861528 (CHEM, a TRPA1 channel antagonist) was administered intrathecally (i.t.) or intraplantarly (i.pl.) in an attempt to reverse the diabetes- or topical mustard oil-induced hyperalgesia. Properties of CHEM as a TRPA1 channel antagonist were assessed using in vitro patch clamp recordings. Results: Diabetes and neurogenic inflammation induced mechanical hyperalgesia. In diabetic animals, hyperalgesia was markedly attenuated by i.t. administration of CHEM at doses 2.5-5.0 ug/rat, whereas 20 ug of CHEM was needed to produce a weak attenuation of diabetic hyperalgesia with i.pl. administrations. When non-diabetic animals with neurogenic inflammation were tested at the site of primary hyperalgesia (the mustard oil-treated area), i.pl. administration of CHEM (20 ug) produced a weak suppression and i.t. administration (10 ug) no attenuation of hyperalgesia. When tested at the site of secondary (central) hyperalgesia (adjacent to the mustard oil-treated area), i.t. administration of CHEM (10 ug) completely reversed the hyperalgesia induced by neurogenic inflammation. In vitro patch clamp recordings indicated that CHEM is a reversible antagonist of the rat TRPA1 channel. Discussion: The results indicate that spinal TRPA1 channels, probably on central terminals of primary afferent nerve fibers, play an important role in maintenance of central hyperalgesia induced by diabetes or neurogenic inflammation.