Neuromodulation of thoracic intraspinal visceroreceptive transmission by electrical stimulation of spinal dorsal column and somatic afferents in rats

Abstract

Clinical studies have shown that neuromodulation therapies, such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS), reduce symptoms of chronic neuropathic and visceral pain. The neural mechanisms underlying SCS and TENS therapy are poorly understood. The present study was designed to compare the effects of SCS and TENS on spinal neuronal responses to noxious stimuli applied to the heart and esophagus. Direct stimulation of an intercostal nerve (ICNS) was used to simulate the effects of TENS. Extracellular potentials of left thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. SCS (50 Hz, 0.2 ms, 3-5 minutes) at a clinical relevant intensity (90% of motor threshold) was applied on the C1-C2 or C8-T1 ipsilateral spinal segments. Intercostal nerve stimulation (ICNS) at T3 spinal level was performed using the same parameters as SCS. Intrapericardial injection of bradykinin (IB, 10 microg/mL, 0.2 mL, 1 minute) was used as the noxious cardiac stimulus. Noxious thoracic esophageal distension (ED, 0.4 mL, 20 seconds) was produced by water inflation of a latex balloon. C1-C2 SCS suppressed excitatory responses of 16/22 T3 spinal neurons to IB and 25/30 neurons to ED. C8-T1 SCS suppressed excitatory responses of 10/15 spinal neurons to IB and 17/23 neurons to ED. ICNS suppressed excitatory responses of 9/12 spinal neurons to IB and 17/22 neurons to ED. These data showed that SCS and ICNS modulated excitatory responses of T3 spinal neurons to noxious stimulation of the heart and esophagus.

Perspective: Neuromodulation of noxious cardiac and esophageal inputs onto thoracic spinal neurons by spinal cord and intercostal nerves stimulation observed in the present study may help account for therapeutic effects on thoracic visceral pain by activating the spinal dorsal column or somatic afferents.

Fig. 1

Inhibitory effects of spinal cord stimulation (SCS) and intercostal nerve stimulation (ICNS) on excitatory responses of upper thoracic (T3) spinal neurons to intrapericardial bradykinin (IB, 10 μg/ml, 0.2 ml). A: excitatory response of a spinal neuron to IB that was suppressed by C1–C2 SCS. B: excitatory response of a spinal neuron to IB that was suppressed by C8-T1 SCS. C: excitatory response of a spinal neuron to IB that was suppressed by ICNS. Left panels are control responses; middle panels are responses during SCS; and right panels are responses recovery.

Fig. 2

A summary for effects of SCS and ICNS on excitatory responses of upper thoracic (T3) spinal neurons to noxious cardiac and esophageal stimuli. A: effects on responses to intrapericardial bradykinin (IB). * P<0.05, ** P<0.01 compared to corresponding neuronal responses to IB before and after SCS or ICNS. B: effects on responses to noxious esophageal distension (ED). * P<0.01 compared to corresponding neuronal responses to ED before and after SCS or ICNS.

Fig. 3

Inhibitory effects of spinal cord stimulation (SCS) and intercostal nerve stimulation (ICNS) on excitatory responses of upper thoracic (T3) spinal neurons to noxious esophageal distension (ED, 0.4 ml, 20 s). A: excitatory response of a spinal neuron to ED that was suppressed by C1–C2 SCS. B: excitatory response of a neuron to ED that was suppressed by C8-T1 SCS. C: excitatory response of a neuron to ED that was suppressed by ICNS. Panels are arranged as in Fig. 1.