gastrin-releasing-peptide and seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide

Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B) subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKCγ-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities.

Topics: Animals; Animals, Newborn; Capsaicin; Cell Count; Chloroquine; Embryo, Mammalian; Ganglia, Spinal; Gastrin-Releasing Peptide; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mice; Mice, Transgenic; Muscle Proteins; Neurons; Oligopeptides; Pain; Physical Stimulation; Protein Kinase C; Protein Precursors; Pruritus; Psychomotor Performance; Sensation; Somatostatin; Tachykinins; Vesicular Glutamate Transport Protein 1