Local cooling alters neural mechanisms producing changes in peripheral blood flow by spinal cord stimulation

This study was performed to investigate the respective role of sensory afferent and sympathetic fibers in peripheral vasodilatation induced by spinal cord stimulation at different hindpaw skin temperatures. Cooling the skin was used as a strategy to enhance sympathetic activity [Am. J. Physiol.: Heart Circ. Physiol. 263 (1992) H1197]. Cutaneous blood flow in the footpad of anesthetized rats was recorded using laser Doppler flowmetry. Local cooling (<25 degrees C) or moderate local cooling (25-28 degrees C) of the hindpaw was produced with a cooling copper coil. Spinal cord stimulation delivered at clinically relevant parameters and with 30%, 60%, and 90% of motor threshold induced the early phase of vasodilatation in the cooled and the moderately cooled hindpaw. In addition, spinal cord stimulation at 90% of motor threshold produced the late phase of vasodilatation only in the cooled hindpaw, which was possible to block by the autonomic ganglion-blocking agent, hexamethonium. The early responses to spinal cord stimulation in the moderately cooled hindpaw were not affected by hexamethonium. In contrast, both the early and the late phase responses were eliminated by CGRP (8-37), an antagonist of the calcitonin gene-related peptide receptor. After dorsal rhizotomy, spinal cord stimulation at 90% of motor threshold elicited hexamethonium-sensitive vasodilatation in the cooled hindpaw (late phase). These results suggest that spinal cord stimulation-induced vasodilatation in the cooled hindpaw (<25 degrees C) is mediated via both the sensory afferent (early phase of vasodilatation) and via suppression of the sympathetic efferent activity (late phase) although the threshold for vasodilatation via the sympathetic efferent fibers is higher than that via sensory nerves. In contrast, vasodilatation via sensory afferent fibers may predominate with moderate temperatures (25-28 degrees C). Thus, two complementary mechanisms for spinal cord stimulation-induced vasodilatation may exist depending on the basal sympathetic tone.

[1]  F. M. Clark,et al.  Anatomical evidence for genetic differences in the innervation of the rat spinal cord by noradrenergic locus coeruleus neurons , 1992, Brain Research.

[2]  M. Fukase,et al.  Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37). , 1989, The American journal of physiology.

[3]  K. Hagbarth,et al.  Thermoregulatory and rhythm‐generating mechanisms governing the sudomotor and vasoconstrictor outflow in human cutaneous nerves. , 1980, The Journal of physiology.

[4]  D L Kellogg,et al.  Reflex control of active cutaneous vasodilation by skin temperature in humans. , 1994, The American journal of physiology.

[5]  R. Freedman,et al.  Local temperature modulates alpha 1- and alpha 2-adrenergic vasoconstriction in men. , 1992, The American journal of physiology.

[6]  M. A. Gilinsky,et al.  Effects of slow and rapid cooling on catecholamine concentration in arterial plasma and the skin. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

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

[8]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[9]  L. Timmermann,et al.  Functional evidence for the differential control of superficial and deep blood vessels by sympathetic vasoconstrictor and primary afferent vasodilator fibres in rat hairless skin , 1998, Experimental Brain Research.

[10]  G. Wasner,et al.  Interaction of sympathetic vasoconstriction and antidromic vasodilatation in the control of skin blood flow , 1997, Experimental Brain Research.

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

[12]  D L Kellogg,et al.  Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. , 1993, The American journal of physiology.

[13]  L. Illis,et al.  Spinal cord stimulation in peripheral vascular disease. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[14]  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.

[15]  Epidural spinal cord stimulation in the treatment of severe peripheral arterial occlusive disease , 1994 .

[16]  J. Faber Effect of local tissue cooling on microvascular smooth muscle and postjunctional alpha 2-adrenoceptors. , 1988, The American journal of physiology.

[17]  D. DiPette,et al.  α 2-Adrenergic receptor activation inhibits calcitonin gene-related peptide expression in cultured dorsal root ganglia neurons , 1998, Brain Research.

[18]  E. McLachlan,et al.  The effect of temperature on neuromuscular transmission in the main caudal artery of the rat. , 1988, The Journal of physiology.

[19]  S. McMahon,et al.  Increase of blood flow in skin and spinal cord following activation of small diameter primary afferents , 1990, Brain Research.

[20]  M. van Kleef,et al.  Pain Relief in Complex Regional Pain Syndrome due to Spinal Cord Stimulation Does Not Depend on Vasodilation , 2000, Anesthesiology.

[21]  K. Barron,et al.  Reevaluation of the Role of the Sympathetic Nervous System in Cutaneous Vasodilation during Dorsal Spinal Cord Stimulation: Are Multiple Mechanisms Active? , 1998, Neuromodulation : journal of the International Neuromodulation Society.

[22]  M. Prins,et al.  Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial. , 1999, Journal of vascular surgery.

[23]  D. Yeomans,et al.  The function of noradrenergic neurons in mediating antinociception induced by electrical stimulation of the locus coeruleus in two different sources of Sprague-Dawley rats , 1993, Brain Research.

[24]  T. Lundeberg,et al.  Preemptive spinal cord stimulation reduces ischemia in an animal model of vasospasm. , 1995, Neurosurgery.

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

[26]  K. Barron,et al.  Spinal integration of antidromic mediated cutaneous vasodilation during dorsal spinal cord stimulation in the rat , 1999, Neuroscience Letters.

[27]  Shealy Cn,et al.  Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. , 1967 .

[28]  H C de Vet,et al.  Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. , 2000, The New England journal of medicine.

[29]  A W Ghajar,et al.  The differential effect of the level of spinal cord stimulation on patients with advanced peripheral vascular disease in the lower limbs. , 1998, British journal of neurosurgery.

[30]  C. Sollerman,et al.  Cooling enhances alpha 2-adrenoceptor-mediated vasoconstriction in human hand veins. , 1990, Acta physiologica Scandinavica.

[31]  M. Meglio,et al.  Pain control and improvement of peripheral blood flow following epidural spinal cord stimulation: case report. , 1981, Journal of neurosurgery.

[32]  B. Linderoth,et al.  Physiology of Spinal Cord Stimulation: Review and Update , 1999, Neuromodulation : journal of the International Neuromodulation Society.

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

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

[35]  X. Hua,et al.  Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord , 1997, The Journal of Neuroscience.

[36]  C A Carlsson,et al.  Epidural Electrical Stimulation in Severe Limb Ischemia: Pain Relief, Increased Blood Flow, and a Possible Limb‐saving Effect , 1985, Annals of surgery.

[37]  B. Wallin,et al.  Peripheral sympathetic neural activity in conscious humans. , 1988, Annual review of physiology.