Characterization of Wide Dynamic Range Neurons in the Deep Dorsal Horn of the Spinal Cord in Preprotachykinin-A Null Mice In Vivo

Abstract

We previously reported that mice with a deletion of the preprotachykinin-A ( pptA) gene, from which substance P (SP) and neurokinin A (NKA) are derived, exhibit reduced behavioral responses to intense stimuli, but that behavioral hypersensitivity after injury is unaltered. To understand the contribution of SP and NKA to nociceptive transmission in the spinal cord, we recorded single-unit activity from wide dynamic range neurons in the lamina V region of the lumbar dorsal horn of urethane-anesthetized wild-type and ppt-A null mutant (–/–) mice. We found that intensity coding to thermal stimuli was largely preserved in the ppt-A –/– mice. Neither the peak stimulus-evoked firing nor the neuronal activity during the initial phase (0–4 s) of the 41–49°C thermal stimuli differed between the genotypes. However, electrophysiological responses during the late phase of the stimulus (5–10 s) and poststimulus (11–25 s) were significantly reduced in ppt-A –/– mice. To activate C-fibers and to sensitize the dorsal horn neurons we applied mustard oil (MO) topically to the hindpaw. We found that neither total MO-evoked activity nor sensitization to subsequent stimuli differed between the wild-type and ppt-A –/– mice. However, the time course of the sensitization and the magnitude of the poststimulus discharges were reduced in ppt-A –/– mice. We conclude that SP and/or NKA are not required for intensity coding or sensitization of nociresponsive neurons in the spinal cord, but that these peptides prolong thermal stimulus-evoked responses. Thus whereas behavioral hypersensitivity after injury is preserved in ppt-A –/– mice, our results suggest that the magnitude and duration of these behavioral responses would be reduced in the absence of SP and/or NKA.