Pacemaker Neurons within Newborn Spinal Pain Circuits

Spontaneous activity driven by pacemaker neurons, defined by their intrinsic ability to generate rhythmic burst firing, contributes to the development of sensory circuits in many regions of the immature CNS. However, it is unknown whether pacemaker-like neurons are present within central pain pathways in the neonate. Here, we provide evidence that a subpopulation of glutamatergic interneurons within lamina I of the rat spinal cord exhibits oscillatory burst firing during early life, which occurs independently of fast synaptic transmission. Pacemaker neurons were distinguished by a higher ratio of persistent, voltage-gated Na+ conductance to leak membrane conductance (g(Na,P)/g(leak)) compared with adjacent, nonbursting lamina I neurons. The activation of high-threshold (N-type and L-type) voltage-gated Ca2+ channels also facilitated rhythmic burst firing by triggering intracellular Ca2+ signaling. Bursting neurons received direct projections from high-threshold sensory afferents but transmitted nociceptive signals with poor fidelity while in the bursting mode. The observation that pacemaker neurons send axon collaterals throughout the neonatal spinal cord raises the possibility that intrinsic burst firing could provide an endogenous drive to the developing sensorimotor networks that mediate spinal pain reflexes.