Sensory fibers containing vanilloid receptor-1 (VR-1) mediate spinal cord stimulation-induced vasodilation

BACKGROUND AND AIMS Spinal cord stimulation (SCS) is used to improve peripheral blood flow in selected populations of patients with ischemia of the extremities. Previous studies show that antidromic activation of sensory fibers is an important mechanism that contributes to SCS-induced vasodilation. However, the characteristics of sensory fibers involved in vasodilation are not fully known. This study investigated the contribution of vanilloid receptor type 1 (VR-1) containing fibers to SCS-induced vasodilation. METHODS A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal cord segments (L2-L3) in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flows from both ipsilateral (left) and contralateral (right) hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS (50 Hz; 0.2 ms) was applied through the ball electrode at 30%, 60%, 90% and 300% of motor threshold (MT). Resiniferatoxin (RTX), an ultra potent analog of capsaicin and VR-1 receptor agonist, was used to suppress the activities of VR-1 containing sensory fibers. RESULTS SCS at 30%, 60%, 90% and also at 300% of MT significantly increased cutaneous blood flow in the ipsilateral foot pad compared to that in the contralateral side. RTX (2 microg/kg, i.v.) significantly attenuated SCS-induced vasodilation of the ipsilateral side (P<0.05, n=7) compared with responses prior to RTX administration. A pledget of cotton soaked with RTX (2 microg/ml) placed on L2-L3 spinal cord significantly decreased SCS-induced vasodilation of the ipsilateral side at 30%, 60%, 90% and 300% of MT (P<0.05, n=7) compared with responses prior to RTX administration. Additionally, topical application of a pledget of cotton soaked with RTX (2 microg/ml) on the sciatic nerve at the middle level of the thigh or on the tibial nerve at the lower level of the lower hindlimb also decreased SCS-induced vasodilation (n=5). CONCLUSION SCS-induced vasodilation is predominantly mediated via VR-1 containing sensory fibers.

[1]  Bengt Linderoth,et al.  Mechanisms of sustained cutaneous vasodilation induced by spinal cord stimulation , 2004, Autonomic Neuroscience.

[2]  Bengt Linderoth,et al.  Local cooling alters neural mechanisms producing changes in peripheral blood flow by spinal cord stimulation , 2003, Autonomic Neuroscience.

[3]  A. Cook,et al.  Vascular disease of extremities. Electric stimulation of spinal cord and posterior roots. , 1976, New York state journal of medicine.

[4]  P. Vaishnava,et al.  Capsaicin sensitive-sensory nerves and blood pressure regulation. , 2003, Current medicinal chemistry. Cardiovascular and hematological agents.

[5]  J. González-Darder,et al.  Spinal cord stimulation in peripheral arterial disease. A cooperative study. , 1986, Journal of neurosurgery.

[6]  B. Meyerson,et al.  Peripheral vasodilatation after spinal cord stimulation: animal studies of putative effector mechanisms. , 1991, Neurosurgery.

[7]  D. Slaaf,et al.  Epidural Spinal Cord Electrical Stimulation Improves Microvascular Blood Flow in Severe Limb Ischemia , 1988, Annals of surgery.

[8]  Bengt Linderoth,et al.  Low intensity spinal cord stimulation may induce cutaneous vasodilation via CGRP release , 2001, Brain Research.

[9]  B. Meyerson,et al.  Effects of sympathectomy on skin and muscle microcirculation during dorsal column stimulation: animal studies. , 1991, Neurosurgery.

[10]  Bengt Linderoth,et al.  Role of primary afferents in spinal cord stimulation-induced vasodilation: characterization of fiber types , 2003, Brain Research.

[11]  S. Brain,et al.  Effect of a calcitonin gene‐related peptide antagonist (CGRP8–37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve , 1993, British journal of pharmacology.

[12]  K. Alloway,et al.  Resiniferatoxin Induces Paradoxical Changes in Thermal and Mechanical Sensitivities in Rats: Mechanism of Action , 2003, The Journal of Neuroscience.

[13]  De-Pei Li,et al.  Cardiac vanilloid receptor 1‐expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats , 2003, The Journal of physiology.

[14]  M. Meglio,et al.  Spinal cord stimulation affects the central mechanisms of regulation of heart rate. , 1986, Applied neurophysiology.

[15]  M. Meglio,et al.  Spinal cord stimulation in management of chronic pain. A 9-year experience. , 1989, Journal of neurosurgery.

[16]  B. Meyerson,et al.  Sympathetic mediation of peripheral vasodilation induced by spinal cord stimulation: animal studies of the role of cholinergic and adrenergic receptor subtypes. , 1994, Neurosurgery.

[17]  T. Imamura,et al.  Endogenous calcitonin gene-related peptide mediates nonadrenergic noncholinergic depressor response to spinal cord stimulation in the pithed rat. , 1992, Circulation research.

[18]  T. Cameron,et al.  Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. , 2004, Journal of neurosurgery.

[19]  W. Bayliss On the origin from the spinal cord of the vaso‐dilator fibres of the hind‐limb, and on the nature of these fibres 1 , 1901, The Journal of physiology.

[20]  M J Chandler,et al.  Cutaneous vasodilation during dorsal column stimulation is mediated by dorsal roots and CGRP. , 1997, The American journal of physiology.

[21]  W. Jänig,et al.  Small diameter myelinated afferents produce vasodilatation but not plasma extravasation in rat skin. , 1989, The Journal of physiology.

[22]  Donna H. Wang The vanilloid receptor and hypertension , 2005, Acta Pharmacologica Sinica.