Abstract:
A neuromodulation system comprises a sensor configured for sensing a blood pressure of a patient, modulation output circuitry configured for conveying electrical modulation energy to at least one electrode, and a controller/processor coupled to the sensor and the modulation output circuitry. The controller/processor is configured for comparing the blood pressure sensed by the sensor to a first threshold blood pressure, and instructing the modulation output circuitry to convey the electrical modulation energy to the at least one electrode if the sensed blood pressure is greater than the first threshold blood pressure. A method for treating chronic hypertension comprises applying electrical modulation energy to a neural target site, thereby modulating an afferent nerve innervating a patient&#39;s kidney, thereby treating the chronic hypertension.

Description:
RELATED APPLICATION DATA 
       [0001]    The present application claims the benefit under 35 U.S.C. §119 to U.S. provisional patent application Ser. No. 61/703,609, filed Sep. 20, 2012. The foregoing application is hereby incorporated by reference into the present application in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to tissue stimulation systems, and more particularly, to electrical stimulation systems for treating hypertension in patients. 
       BACKGROUND OF THE INVENTION 
       [0003]    Implantable neurostimulation systems have proven therapeutic in a wide variety of diseases and disorders. For example, Spinal Cord Stimulation (SCS) techniques, which directly stimulate the spinal cord tissue of the patient, have long been accepted as a therapeutic modality for the treatment of chronic neuropathic pain syndromes, and the application of spinal cord stimulation has expanded to include additional applications, such as angina pectoralis, peripheral vascular disease, and incontinence, among others. Spinal cord stimulation is also a promising option for patients suffering from motor disorders, such as Parkinson&#39;s Disease, Dystonia and essential tremor. 
         [0004]    An implantable SCS system typically includes one or more electrode-carrying stimulation leads, which are implanted at a stimulation site in proximity to the spinal cord tissue of the patient, and a neurostimulator implanted remotely from the stimulation site, but coupled either directly to the stimulation lead(s) or indirectly to the stimulation lead(s) via a lead extension. The neurostimulation system may further include a handheld patient programmer to remotely instruct the neurostimulator to generate electrical stimulation pulses in accordance with selected stimulation parameters. The handheld programmer may, itself, be programmed by a technician attending the patient, for example, by using a Clinician&#39;s Programmer (CP), which typically includes a general purpose computer, such as a laptop, with a programming software package installed thereon. 
         [0005]    Thus, programmed electrical pulses can be delivered from the neurostimulator to the stimulation lead(s) to stimulate or activate a volume of the spinal cord tissue. In particular, electrical stimulation energy conveyed to the electrodes creates an electrical field, which, when strong enough, depolarizes (or “stimulates”) the neural fibers within the spinal cord beyond a threshold level, thereby inducing the firing of action potentials (APs) that propagate along the neural fibers to provide the desired efficacious therapy to the patient. 
         [0006]    Hypertension is a health problem affecting millions of people, requiring considerable expenditure of medical resources as well as imposing significant burdens on those who suffer from this condition. Hypertension generally involves resistance to the free flow of blood within a patient&#39;s vasculature, often caused by reduced volume stemming from plaque, lesions, and the like. Because blood vessels do not permit easy flow, the patient&#39;s heart must pump at higher pressure. In addition, reduced cross-sectional area results in higher flow velocity. In consequence, a patient&#39;s blood pressure may enter into the range of hypertension i.e. greater than 140 mm Hg systolic/90 mm Hg diastolic. 
         [0007]    It has been recognized that the kidneys play a key role in blood pressure regulation, and a number of hypertension treatment approaches have focused on the kidneys, providing a number of pharmaceutical compounds aimed at promoting blood to flow through these organs. One treatment option has been to destroy some or all of the nerves innervating the kidneys through ablation, a process in which an ablation electrode, carried in an instrument such as an endoscope, is introduced into a patient&#39;s vasculature and navigated to a position within the renal artery. Electrical energy, operating at radio frequencies, is applied to the electrode, resulting in destruction of the renal nerves. This process, of course, is irreversible and carries the possibility of undesirable side effects. The process is nonetheless effective in combating hypertension. 
         [0008]    Thus, a need remains for a process that can ameliorate hypertension without permanently affecting the renal nervous system. 
       SUMMARY OF THE INVENTION 
       [0009]    In accordance with another aspect of the present inventions, a neuromodulation system may include a sensor configured for sensing a parameter correlatable to blood pressure of a patient, modulation output circuitry configured for conveying electrical modulation energy to at least one electrode, and a controller/processor coupled to the sensor and the modulation output circuitry. The controller/processor is configured for comparing the sensed parameter to a first threshold and instructing the modulation output circuitry to convey the electrical modulation energy to the at least one electrode based on the comparison. If the sensed parameter comprises a sensed blood pressure, and the first threshold comprises a first threshold blood pressure (e.g., 140 mm Hg systolic/90 mm Hg diastolic), the controller/processor may be configured for instructing the modulation output circuitry to convey the electrical modulation energy to the electrode(s) if the sensed blood pressure is greater than the first threshold blood pressure. In one embodiment, the controller/processor may be configured for comparing the blood pressure sensed by the sensor to a second threshold blood pressure (e.g., a value less than the first threshold, e.g., in a range of 100-140 mm Hg systolic/60-90 mm Hg), and instructing the stimulation output circuitry to cease conveying the electrical modulation energy to the at least one electrode if the sensed blood pressure is less than the second threshold blood pressure. The neuromodulation system may include a biocompatible casing housing the modulation output circuitry and the controller/processor. Further, the neuromodulation system may include the electrode(s). 
         [0010]    In accordance with another aspect of the present inventions, a method for treating a patient from chronic hypertension is provided. The method comprises applying electrical modulation energy to a neural target site, thereby modulating an afferent nerve fiber (e.g., evoking action potentials along the nerve fiber or blocking action potentials along the nerve fiber) innervating a kidney of the patient, thereby treating the chronic hypertension. The neural target site may, e.g., be located on the afferent nerve fiber, itself, or may be located on a nerve fiber (e.g., an efferent nerve fiber) that synapses to the afferent nerve fiber. The neural target site may be, e.g., located on a spinal cord of the patient (e.g., the dorsal column (DC) nerve fiber), a dorsal root (DR) nerve fiber, or a peripheral nerve fiber. The nerve fiber may be an automatic nerve fiber; e.g., a sympathetic nerve fiber, in which case, the neural target site may be located at an L1-L3 spinal level, or a parasympathetic nerve fiber, in which case, the neural target site may be located at an S2-S4 spinal level. The electrical modulation energy may be epidurally applied to the target site on the afferent nerve fiber. In some embodiments, however, the electrical modulation energy may be applied transcutaneously to the target site. The patient may have a blood pressure greater than 140 mm Hg systolic/90 mm Hg diastolic prior to the application of the modulation energy to the target site on the afferent nerve fiber. The patient may have a blood pressure in the range of 100-140 mm Hg systolic/60-90 mm Hg diastolic during the application of the modulation energy to the target site on the afferent nerve fiber. 
         [0011]    Other and further aspects and features of the invention will be evident from reading the following detailed description of the preferred embodiments, which are intended to illustrate, not limit, the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0012]    The drawings illustrate the design and utility of preferred embodiments of the present invention, in which similar elements are referred to by common reference numerals. In order to better appreciate how the above-recited and other advantages and objects of the present inventions are obtained, a more particular description of the present inventions briefly described above will be rendered by reference to specific embodiments thereof, which are illustrated in the accompanying drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which: 
           [0013]      FIG. 1  is a plan view of a neuromodulation system constructed in accordance with one embodiment of the present inventions; 
           [0014]      FIG. 2  is a plan view of an implantable pulse generator (IPG) and three percutaneous modulation leads used in the neuromodulation system of  FIG. 1 ; 
           [0015]      FIG. 3  is a plan view of an implantable pulse generator (IPG) and a surgical paddle lead used in the neuromodulation system of  FIG. 1 ; 
           [0016]      FIG. 4  is a pictorial/sectional view of the spinal cord and spinal nerves; 
           [0017]      FIG. 5  is a schematic view showing various modulation regions relative to the spinal cord and spinal nerves in accordance with the present invention; 
           [0018]      FIG. 6A  is a schematic view showing a single-electrode arrangement relative to the spinal cord and spinal nerves in accordance with the present invention; 
           [0019]      FIG. 6B  is a schematic view showing the spinal column, showing the positioning of electrodes in accordance with the present invention; 
           [0020]      FIG. 7  is a schematic view showing another single-electrode arrangement relative to the spinal cord and spinal nerves in accordance with the present invention; 
           [0021]      FIG. 8  is a schematic view showing a double-electrode arrangement relative to the spinal cord and spinal nerves in accordance with the present invention; and 
           [0022]      FIG. 9  is a schematic view showing a single-electrode arrangement near peripheral nerves in accordance with the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0023]    Turning first to  FIG. 1 , an exemplary neuromodulation system  10  generally comprises a plurality of modulation leads  12  (in this case, three), an implantable pulse generator (IPG)  14  (or alternatively RF receiver-stimulator), an external remote control (RC)  16 , a Clinician&#39;s Programmer (CP)  18 , an External Trial Stimulator (ETS)  20 , and an external charger  22 . 
         [0024]    The IPG  14  is physically connected via one or more lead extensions  24  to the modulation leads  12 , which carry a plurality of electrodes  26  arranged in an array. The modulation leads  12  are illustrated as percutaneous leads in  FIG. 1 , although as will be described in further detail below, a surgical paddle lead can be used in place of the percutaneous leads. As will also be described in further detail below, the IPG  14  includes pulse generation circuitry ( FIG. 2 ) that delivers electrical modulation energy in the form of a pulsed electrical waveform (i.e., a temporal series of electrical pulses) to the array of electrodes  26  in accordance with a set of modulation parameters. 
         [0025]    The ETS  20  may also be physically connected via the percutaneous lead extensions  28  and external cable  30  to the neuromodulation leads  12 . The ETS  20 , which has similar pulse generation circuitry as the IPG  14 , also delivers electrical modulation energy in the form of a pulse electrical waveform to the array of electrodes  26  in accordance with a set of modulation parameters. The major difference between the ETS  20  and the IPG  14  is that the ETS  20  is a non-implantable device that is used on a trial basis after the neuromodulation leads  12  have been implanted and prior to implantation of the IPG  14 , to test the responsiveness of the modulation that is to be provided. Thus, any functions described herein with respect to the IPG  14  can likewise be performed with respect to the ETS  20 . 
         [0026]    The RC  16  may be used to telemetrically control the ETS  20  via a bi-directional RF communications link  32 . Once the IPG  14  and neuromodulation leads  12  are implanted, the RC  16  may be used to telemetrically control the IPG  14  via a bi-directional RF communications link  34 . Such control allows the IPG  14  to be turned on or off and to be programmed with different modulation parameter sets. The IPG  14  may also be operated to modify the programmed modulation parameters to actively control the characteristics of the electrical modulation energy output by the IPG  14 . As will be described in further detail below, the CP  18  provides clinician detailed modulation parameters for programming the IPG  14  and ETS  20  in the operating room and in follow-up sessions. 
         [0027]    The CP  18  may perform this function by indirectly communicating with the IPG  14  or ETS  20 , through the RC  16 , via an IR communications link  36 . Alternatively, the CP  18  may directly communicate with the IPG  14  or ETS  20  via an RF communications link (not shown). The clinician detailed modulation parameters provided by the CP  18  are also used to program the RC  16 , so that the modulation parameters can be subsequently modified by operation of the RC  16  in a stand-alone mode (i.e., without the assistance of the CP  18 ). The charger  22  may also communicate with the IPG  14  via a communications link  38 . 
         [0028]    The neuromodulation system  10  further includes a blood pressure sensor  58 . A number of conventional pressure sensing devices and techniques are available to the art for sensing such factors. To sense blood pressure, for example, one could choose from among sensors bases on mechanical, piezoelectric, electromagnetic, or other technologies. The sensor  58  may be implanted within the patient&#39;s body, or one could employ a sensor  58  capable or remotely sensing the desired factor from a position outside the patient&#39;s body. In either instance, the sensor  58  communicates with the IPG  14  and the external RC  16  via bi-directional communication links  62  and  60 , respectively, or via an electrical conductor (not shown). These communication links may function via RF or other suitable technology. In alternative embodiments, other types of sensors that measure parameters correlatable to blood pressure (e.g., EKG using beat-to-beat (R-R) variability to globally assess autonomic tone) can be used. 
         [0029]    For purposes of brevity, the details of the RC  16 , CP  18 , ETS  20 , and external charger  22  will not be described herein. Details of exemplary embodiments of these devices are disclosed in U.S. Pat. No. 6,895,280, which is expressly incorporated herein by reference. 
         [0030]    Referring now to  FIG. 3 , the external features of the modulation leads  12  and the IPG  14  will be briefly described. Each of the modulation leads  12  has eight electrodes  26  (respectively labeled E1-E8, E9-E16, and E17-E24). The actual number and shape of leads and electrodes will, of course, vary according to the intended application. Further details describing the construction and method of manufacturing percutaneous modulation leads are disclosed in U.S. patent application Ser. No. 11/689,918, entitled “Lead Assembly and Method of Making Same,” and U.S. patent application Ser. No. 11/565,547, entitled “Cylindrical Multi-Contact Electrode Lead for Neural Modulation and Method of Making Same,” the disclosures of which are expressly incorporated herein by reference. 
         [0031]    Alternatively, as illustrated in  FIG. 4 , the modulation lead  12  takes the form of a surgical paddle lead  48  on which electrodes  26  are arranged in a two-dimensional array in three columns (respectively labeled E1-E5, E6-E10, and E11-E15) along the axis of the modulation lead  12 . In the illustrated embodiment, five rows of electrodes  26  are provided, although any number of rows of electrodes can be used. Each row of the electrodes  26  is arranged in a line transversely to the axis of the lead  12 . The actual number of leads and electrodes will, of course, vary according to the intended application. Further details regarding the construction and method of manufacture of surgical paddle leads are disclosed in U.S. patent application Ser. No. 11/319,291, entitled “Stimulator Leads and Methods for Lead Fabrication,” the disclosure of which is expressly incorporated herein by reference. 
         [0032]    In each of the embodiments illustrated in  FIGS. 3 and 4 , the IPG  14  includes an outer case  44  for housing the electronic and other components (described in further detail below). The outer case  44  is composed of an electrically conductive, biocompatible material, such as titanium, and forms a hermetically sealed compartment, wherein the internal electronics are protected from the body tissue and fluids. In some cases, the outer case  44  may serve as an electrode. The IPG  14  further comprises a connector  46  to which the proximal ends of the modulation leads  12  mate in a manner that electrically couples the electrodes  26  to the internal electronics (described in further detail below) within the outer case  44 . To this end, the connector  46  includes one or more ports (three ports  50  or three percutaneous leads or one port for the surgical paddle lead) for receiving the proximal end(s) of the modulation lead(s)  12 . In the case, where the lead extensions  24  (shown in  FIG. 1 ) are used, the port(s)  50  may instead receive the proximal ends of such lead extensions  24 . 
         [0033]    Further, IPG  14  may include electronic components such as a telemetry circuit  52 , a microcontroller  54 , a battery  56 , and other suitable components known to those skilled in the art. The microcontroller  54  executes a suitable program stored in memory (not shown), for directing and controlling the neuromodulation performed by IPG  14 . Telemetry circuitry  52  (including antenna is configured for receiving programming data (e.g., the operating program and/or neuromodulation parameters) from the RC  16  in an appropriate modulated carrier signal, and demodulating the carrier signal to recover the programming data, which programming data is then stored in memory. The battery  56 , which may be a rechargeable lithium-ion or lithium-ion polymer battery, provides operating power to IPG  14 . 
         [0034]    In addition, the IPG  14  includes pulse generation circuitry  57  that provides electrical conditioning and modulation energy in the form of a pulsed electrical waveform to the electrode array  26  in accordance with a set of modulation parameters programmed into the IPG  14 . Such modulation parameters may comprise electrode combinations, which define the electrodes that are activated as anodes (positive), cathodes (negative), and turned off (zero), percentage of modulation energy assigned to each electrode of the array of electrodes  26  (fractionalized electrode configurations), and electrical pulse parameters, which define the pulse amplitude (measured in milliamps or volts depending on whether the IPG  14  supplies constant current or constant voltage to the array of electrodes  26 ), pulse width (measured in microseconds), pulse rate (measured in pulses per second), and burst rate (measured as the modulation on duration X and modulation off duration Y). 
         [0035]    Electrical modulation will occur between two (or more) activated electrodes, one of which may be the IPG case  44 . Simulation energy may be transmitted to the tissue in a monopolar or multipolar (e.g., bipolar, tripolar, etc.) fashion. Monopolar modulation occurs when a selected one of the lead electrodes  26  is activated along with the case  44  of the IPG  14 , so that modulation energy is transmitted between the selected electrode  26  and the case  44 . Bipolar modulation occurs when two of the lead electrodes  26  are activated as anode and cathode, so that modulation energy is transmitted between the selected electrodes  26 . For example, an electrode on one lead  12  may be activated as an anode at the same time that an electrode on the same lead or another lead  12  is activated as a cathode. Tripolar modulation occurs when three of the lead electrodes  26  are activated, two as anodes and the remaining one as a cathode, or two as cathodes and the remaining one as an anode. For example, two electrodes on one lead  12  may be activated as anodes at the same time that an electrode on another lead  12  is activated as a cathode. 
         [0036]    The modulation energy may be delivered between electrodes as monophasic electrical energy or multiphasic electrical energy. Monophasic electrical energy includes a series of pulses that are either all positive (anodic) or all negative (cathodic). Multiphasic electrical energy includes a series of pulses that alternate between positive and negative. For example, multiphasic electrical energy may include a series of biphasic pulses, with each biphasic pulse including a cathodic (negative) modulation pulse and an anodic (positive) recharge pulse that is generated after the modulation pulse to prevent direct current charge transfer through the tissue, thereby avoiding electrode degradation and cell trauma. That is, charge is conveyed through the electrode-tissue interface via current at an electrode during a modulation period (the length of the modulation pulse), and then pulled back off the electrode-tissue interface via an oppositely polarized current at the same electrode during a recharge period (the length of the recharge pulse). 
         [0037]    Referring now to  FIG. 4 , the portions of the spinal cord  100  that are relevant to the present inventions will be described. The spinal cord  100  is divided into three columns: the dorsal column  102 , the ventral column  104 , and the lateral columns  106 . One lateral column lies on either side of the spinal cord  100 . Similarly, the butterfly-shaped gray matter of the spinal cord  100  is divided into the dorsal horn  108 , the ventral horn  110 , and the lateral horn  112 . A ventral median fissure  109  divides the spinal cord  100  into two lateral halves. 
         [0038]    A group of motor nerve rootlets (ventral root nerve fibers)  114  branch off of the ventral horn  110  and combine to form the ventral root (VR)  116 . Similarly, a group of sensory nerve rootlets (dorsal root (DR) nerve fibers)  118  branch off of the dorsal horn  108  and combine to form the dorsal root  120 . The dorsal root  120  and the ventral root  116  combine to form the spinal nerve  122 , which innervates peripheral regions (e.g., arms, legs, etc.) of the patient&#39;s body. It will be noted that symmetrical motor nerve rootlets, ventral root, sensory nerve rootlets, dorsal root, and spinal nerve are located on the opposite side of spinal cord  100 , but these elements are omitted for simplicity. A number of spinal nerves branch off the spinal cord. In each patient, there are eight cervical spinal nerves designated C1-08, twelve thoracic spinal nerves designated T1-T12, five lumbar spinal nerves designated L1-L5, and five sacral spinal nerves designated S1-S5. 
         [0039]    The spinal cord  100  is protected by three layers of connective tissue, the dura mater  126 , the arachnoid  124 , and the pia mater  123 , collectively referred to as meninges. Epidural space  128  surrounds the dura mater  126 , and subarachnoid space  127  lies under the arachnoid  124 . The epidural space  128  may be topologically divided into two halves: a ventral epidural space  128   a  and a dorsal epidural space  128   b  (as shown in  FIG. 6A ). 
         [0040]    The neuromodulation system  10  (shown in  FIG. 1 ) may be employed to modulate various neural regions to treat hypertension. Specifically, the neuromodulation system  10  may be configured to modulate afferent nerve fibers innervating a patient&#39;s kidney, resulting in a reduction in the patient&#39;s blood pressure. 
         [0041]    In particular, modulation of the afferent nerve fibers that innervate the kidney, modulation reduces sympathetic tone, which in turn has an electrical sympatholytic effect, producing a reduction in the patient&#39;s blood pressure. That is, modulation of the sympathetic nervous system may block action potentials that down-regulate the sympathetic nervous system, resulting in vasodilation, thus decreasing the patient&#39;s blood pressure. Alternatively, modulation of the parasympathetic nervous system may evoke action potentials that up-regulate the parasympathetic nervous system, resulting in vasodilation, thus decreasing the patient&#39;s blood pressure. Thus, it can appreciated that modulation of the autonomic nervous system (which includes both sympathetic and parasympathetic nerves) may decrease the patient&#39;s blood pressure. 
         [0042]    Three variables affecting that method are the modulation location on the nerve fiber, the particular nerve fiber being chosen for modulation, and the particular modulation parameters used to either evoke action potentials or block action potentials along the nerve fiber. Notably, modulation of a nerve fiber at a pulse rate less 500 Hz may evoke action potentials in that nerve fiber, whereas modulation of a nerve fiber at a pulse rate greater than 1 KHz may block action potentials in that nerve fiber. 
         [0043]    The neuromodulation system  10  may operate in a closed-loop manner to modulate the afferent nerve fibers that innervate the kidney based on sensed blood pressure. For example, the IPG  14  may obtain the detected blood pressure from the sensor  58  via the link  62  and compare it to both a first threshold (e.g., 140 mm Hg systolic/90 mm Hg diastolic) and a second threshold (e.g., somewhere in a range of 100-140 mm Hg systolic/60-90 mm Hg). If the comparison reveals that the detected blood pressure is above the first threshold, and the IPG  14  is currently not stimulating the afferent nerve fibers, the IPG  14  may automatically initiate modulation of the afferent nerve fibers. If the comparison shows that the detected blood pressure is below the second threshold (which may be equal to the first threshold), and the IPG  14  is current stimulating the afferent nerve fibers, the IPG  14  may automatically cease further modulation. Preferably, hysteresis may be built into the closed feedback loop, so that the IPG  14  does not rapidly initiate and cease modulation as the detected blood pressure varies around the first threshold. For example, the second threshold may be substantially less than the first threshold (e.g., by 5 or 10 mmHg). 
         [0044]    Although control of the modulation based on the detected blood pressure has been described with respect to the IPG  14 , it should be appreciated that an external control device may control the modulation based on the detected blood pressure. For example, the RC  16  may obtain the detected blood pressure from the sensor  58  via the link  60  and compare it to both the first and second threshold, and instruct the IPG  14  via the link  34  to either initiate modulation or cease modulation based on this comparison. 
         [0045]    Referring to  FIG. 5 , it is known that sympathetic afferents from the kidneys converge at the inferior mesenteric ganglion (not shown) and then enter the spinal cord via the L1-L3 dorsal roots. As shown, dorsal roots  120   a - 120   c  emerge from lumbar vertebrae L1-L3 and pass through dorsal root ganglia  140   a - 140   c . Among these peripheral nerve fibers are afferent fibers that go on to innervate the kidneys Thus, preferred methods of the present invention employ one or more of the electrodes  26  positioned to block action potentials in afferent nerve fibers in the dorsal column, the dorsal roots, and/or peripheral nerves associated with the L1-L3 vertebra. The modulation regime associated with electrodes  26  are designed to sufficiently modulate the dorsal column, dorsal roots, and/or peripheral nerves, as will be understood by those of skill in the art. 
         [0046]    For example, as shown in  FIGS. 6A and 6B , one or more modulation electrodes  26  may be located within the dorsal epidural space  128   b  adjacent to the respective L1-L3 vertebra of the dorsal column  102 . As another example, a modulation electrode  26  may be located near the dorsal root nerve fiber  118 , positioned toward the dorsal root ganglia  140 , as shown in  FIG. 7 . 
         [0047]    In contrast to  FIGS. 6 and 7 , which either locates the electrode or electrodes  26  adjacent the dorsal column  102  ( FIG. 6 ) or adjacent the dorsal root nerve fiber  118  ( FIG. 7 ), two modulation electrodes  26  are respectively located near the dorsal column  102  and the dorsal root nerve fiber  118  as shown in  FIG. 8 . This arrangement of electrodes may be configured to modulate the two regions simultaneously or in alternating fashion. Here, dorsal column electrode  306  is positioned in relatively close proximity to the DR  120 , and the dorsal root nerve fiber electrode  308  is positioned close to the dorsal root ganglion  140  in the epidural space  128   b.    
         [0048]    As another example shown in  FIG. 9 , an electrode  26  may be located near the peripheral nerve fiber  303 . The peripheral nerve  303  innervates kidney  305 , and the electrode  26  is positioned in a suitable location beyond dorsal root ganglion  140 . 
         [0049]    Alternatively, it is known that parasympathetic afferents from the kidneys converge at the pelvic nerve and then enter the spinal cord via the S2-S4 dorsal roots. Thus, preferred methods of the present invention employ one or more of the electrodes  26  positioned to evoke action potentials in afferent nerve fibers in the dorsal column, the dorsal roots, and/or peripheral nerves associated with the S2-S4 vertebra. The modulation regime associated with electrodes  26  are designed to sufficiently modulate the dorsal column, dorsal roots, and/or peripheral nerves, as will be understood by those of skill in the art. 
         [0050]    Although the particular neural target site has been described as being located on the afferent nerve fiber innervating the kidney, it should be appreciated that the neural target site can be located on any nerve fiber (whether afferent or efferent) that synapses to the afferent nerve fiber that innervating the kidney. If the neural target site is located on an efferent nerve fiber, post-synaptic influence, as well as, perhaps, retrograde conduction of action potentials via efferent nerves, may result in the afferent nerve fibers innervating the kidneys; e.g., via reflex action through the spinal cord. 
         [0051]    Although particular embodiments of the present inventions have been shown and described, it will be understood that it is not intended to limit the present inventions to the preferred embodiments, and it will be obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present inventions. Thus, the present inventions are intended to cover alternatives, modifications, and equivalents, which may be included within the spirit and scope of the present inventions as defined by the claims.