Afferent pathway and neuromodulation of superficial and deeper thoracic spinal neurons receiving noxious pulmonary...

The occurrence of vagally mediated afferent signaling by lung irritants is well known. However, spinal visceral afferent pathways also might be relevant to pulmonary irritation. In the present study, responses and modulation of superficial and deep T3 spinal neurons were examined using inhaled ammonia, and the peripheral afferent fibers were also characterized in part. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Ammonia vapor (0.5, 1.0, 2.0 ml) was injected into the inspiratory line of the ventilator for 20 s. Inhaled ammonia (IA, 1.0 ml) excited 5/6 neurons and inhibited one spinal neuron recorded in superficial laminae, whereas deeper neurons responded with excitatory (E, n = 20), inhibitory (I, n = 4) or biphasic patterns (6 E-I, 3 I-E). Electrical and chemical stimulation of C1-C2 spinal neurons primarily suppressed T3 neuronal responses to IA. Resiniferatoxin (2 microg/kg, i.v.), which desensitizes afferent fibers containing transient receptor potential vanilloid receptor-1 (TRPV-1), abolished excitatory responses of 8/8 neurons to IA. Bilateral cervical vagotomy did not affect IA responses in 5 superficial neurons while 7 deeper neurons showed variable responses. 82% (32/39) of the spinal neurons responding to IA also received convergent noxious inputs from somatic fields in the chest and back areas. These results suggested that superficial and deeper spinal neuronal activation by inhaled ammonia mainly depended upon pulmonary sympathetic afferent fibers expressing TRPV-1. Additionally, C1-C2 spinal neurons, supraspinal sites and vagal afferents modulated the thoracic spinal neuronal responses to lower airway irritation.