Is constant current or constant voltage spinal cord stimulation superior for the suppression of nociceptive visceral and somatic stimuli? A rat model.

OBJECTIVES: This study compares the effects of constant current (CC) and constant voltage (CV) spinal cord stimulation (SCS) at various frequencies and intensities on standard nociceptive measurements in rats, the visceromotor reflex (VMR) and neuronal activity, during noxious visceral and somatic stimuli. MATERIALS AND METHODS: Abdominal muscle electromyographic activity changes were measured to indicate VMR, and extracellular activity of L6-S2 spinal neurons was recorded during somatic (pinching) and noxious visceral stimulation (colorectal distension [CRD], 60 mmHg) in anesthetized rats. A stimulating (unipolar ball) electrode at L2-L3 delivered CC- or CV-SCS at varied frequencies and intensities. RESULTS: CC-SCS reduced VMR evoked by CRD significantly more than CV-SCS (p < 0.05). For neuronal activity, high-frequency CC-SCS (40 and 100 Hz) and CV-SCS (100 Hz) effectively reduced intraspinal somatic nociceptive transmission more than low-frequency SCS (2 Hz). No significant differences were observed between the effects of CC- and CV-SCS on spontaneous activity and nociceptive responses of spinal neurons to noxious CRD following short- (five to ten minutes) or long-term (20-30 min) SCS. CONCLUSIONS: Although high-frequency CC- and CV-SCS may be more useful for the management of somatic pain, CC-SCS may be more effective for treating complex pain systems like visceral hypersensitivity.

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

UNLABELLED: 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.

Roles of peripheral terminals of transient receptor potential vanilloid-1 containing sensory fibers in spinal cord stimulation-induced peripheral vasodilation.

BACKGROUND: Spinal cord stimulation (SCS) is used to relieve ischemic pain and improve peripheral blood flow in selected patients with peripheral arterial diseases. Our previous studies show that antidromic activation of transient receptor potential vanilloid-1 (TRPV1) containing sensory fibers importantly contributes to SCS-induced vasodilation. OBJECTIVES: To determine whether peripheral terminals of TRPV1 containing sensory fibers produces vasodilation that depends upon the release of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) during SCS. METHODS: A unipolar ball electrode was placed on the left dorsal column at lumbar spinal cord segments 2-3 in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flow from left and right hindpaws was recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 30%, 60%, 90% and 300% of motor threshold. Resiniferatoxin (RTX; 2 microg/ml, 100 microl), an ultra potent analog of capsaicin, was injected locally into the left hindpaw to functionally inactivate TRPV-1 containing sensory terminals. In another set of experiments, CGRP(8-37), an antagonist of the CGRP-1 receptor, was injected at 0.06, 0.12 or 0.6 mg/100 microl into the left hindpaw to block CGRP responses; N-omega-nitro-l-arginine methyl ester (L-NAME), a nonselective nitric-oxide synthase (NOS) inhibitor, was injected at 0.02 or 0.2 mg/100 microl into the left hindpaw to block nitric oxide synthesis; (4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, a neuronal NOS inhibitor, was injected at 0.02 or 0.1 mg/100 microl into the left hindpaw to block neuronal nitric oxide synthesis. RESULTS: SCS at all intensities produced vasodilation in the left hindpaw, but not in the right. RTX administration attenuated SCS-induced vasodilation at all intensities in the left hindpaw (P<0.05, n=7) compared with responses before RTX. CGRP(8-37) administration attenuated SCS-induced vasodilation in the left hindpaw in a dose dependent manner (linear regression, P<0.05) compared with responses before CGRP(8-37). In addition, L-NAME at a high dose, but not (4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, decreased SCS-induced vasodilation (P<0.05, n=5). CONCLUSION: While TRPV1, CGRP and NO are known to be localized in the same nerve terminals, our data indicate that SCS-induced vasodilation depends on CGRP release, but not NO release. NO, released from endothelial cells, may be associated with vascular smooth muscle relaxation and peripheral blood flow increase in response to SCS.