We have previously reported that electrical stimulation of cardiac vagal afferents produces an inhibition of the feline's digastric reflex evoked by tooth-pulp stimulation. In the present study, we evaluated whether cardiac vagal afferent stimulation (CVAS) alters the responses of trigeminal sensory neurons to noxious orofacial stimulation in alpha-chloralose-anesthetized cats. A total of 37 trigeminal and trigeminothalamic neurons were recorded from trigeminal nucleus caudalis and trigeminal nucleus oralis. Thirty-five of these 37 neurons were classified as wide-dynamic-range (WDR) neurons because they had cutaneous receptive fields and responded to both noxious heat and non-noxious tactile stimuli. The effects of continuous CVAS (5 Hz, 3 msec, 2 mA) on heat-evoked responses (6 sec 50 degrees C heat pulse) were examined on 32 WDR neurons. CVAS inhibited (21 of 32 neurons), facilitated (5 of 32 neurons) or did not affect neuronal responses (6 of 32 neurons) to noxious heat. The effects of CVAS on heat-evoked responses of trigeminal and trigeminothalamic neurons were equivalent. The effects of intermittent CVAS (7 pulses at 333 Hz, 5 mA, delivered 200 msec prior to the test stimulus) on the responses to electrical test stimuli delivered to the center of a neuron's cutaneous receptive field or to the tooth pulp were also examined. Intermittent CVAS inhibited (15 of 24 neurons), facilitated (4 of 24 neurons) or had no effect (5 of 24 neurons) on A delta-mediated responses evoked by the electrical stimulation of facial skin. Intermittent CVAS either inhibited (8 of 12 neurons) or had no effect (4 of 12 neurons) on C-fiber-mediated responses evoked by electrical stimulation of the facial skin. Eight cells were recorded that received tooth-pulp input. Six of these 8 cells also received afferent input from facial skin, the remaining 2 cells responded only to tooth-pulp stimulation. Intermittent CVAS either inhibited (7 of 8 neurons) or had no effect (1 of 8 neurons) on A delta-mediated responses evoked by electrical stimulation of the tooth pulp. The modulatory actions of intermittent CVAS on trigeminal and trigeminothalamic neuronal responses to convergent afferent input from both skin and tooth pulp were equivalent. The outcomes of this study provide additional evidence that cardiopulmonary vagal afferent stimulation modulates neuronal responses to noxious stimulation and suggest that alterations in cardiopulmonary dynamics may modulate nociception.

We recorded whole cell currents of patch-clamped neurons in stratum pyramidale of CA1 region of rat hippocampal tissue slices. Synaptic currents were evoked by orthodromic stimulation while holding potential of the neuron was varied from hyperpolarized to depolarized levels. Extracellular osmolarity (pi(o)) was lowered by superfusion with artificial cerebrospinal fluid in which NaCl concentration ([NaCl]) was reduced. The effect of low extracellular NaCl was tested in additional trials in which NaCl was substituted by isosmolar fructose. Both lowering of pi(o) and isosmotic lowering of extracellular [NaCl] ([NaCl]o) caused reversible increase of excitatory postsynaptic currents. The effect of lowering pi(o) was concentration dependent, and it was significantly stronger than the effect of equivalent isosmotic lowering of [NaCl]o. Inhibitory postsynaptic currents also increased in many but not in all cases. Lowering of pi(o) caused a prolongation of the time constant of relaxation of the capacitive charging current induced by small hyperpolarizing voltage steps. A virtual input capacitance, calculated by dividing this time constant by the input resistance, increased during hypotonic exposure. Isosmotic lowering of [NaCl]o had no effect on time constant or input capacitance. Depolarizing voltage commands evoked spikelike inward currents presumably representing Na+-dependent action potentials generated outside the voltage-clamped region of the cell. These current spikes became smaller in low pi(o) and in low [NaCl]o. Broader, voltage-dependent, presumably Ca2+-mediated inward currents became more prominent during hypotonic exposure. We conclude that lowering of [NaCl]o causes enhancement of excitatory synaptic transmission. Transmission may be facilitated by the uptake of Ca2+ into presynaptic terminals as well as into postsynaptic target neurons, induced by the low [NaCl]o. Lowering of pi(o) enhances synaptic transmission more than does a corresponding isosmotic lowering of [NaCl]. The excess increase recorded from the cell soma in low pi(o) may in part be due to changing electrotonic length caused by the swelling of dendrites.