Patent Publication Number: US-2006020297-A1

Title: Neurostimulation system with distributed stimulators

Description:
This application claims the benefit of U.S. provisional application No. 60/589,541, filed Jul. 20, 2004, the entire content of which is incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION  
      The invention relates generally to medical devices and, more particularly, to medical devices for delivery of neurostimulation therapy.  
     BACKGROUND  
      A variety of pelvic floor disorders such as urinary control disorders, fecal control disorders, interstitial cystitis, sexual dysfunction, and pelvic pain are influenced by the sacral nerves and other nerves. The organs involved in various bodily functions in the pelvic floor region receive much of their control via the second, third, and fourth sacral nerves, commonly referred to as S2, S3, and S4, respectively. The sacrum, in general, is a large, triangular bone situated at the lower part of the vertebral column, and at the upper and back part of the pelvic cavity. The spinal canal runs throughout the sacrum. The sacral nerves pass through the sacrum via the anterior and posterior sacral foramina. Pelvic organs are also innervated via other nerves, such as the pudendal nerve.  
      Electrical stimulation of the sacral nerves, pudendal nerves, and other nerves of the pelvic floor has been found to offer relief for many pelvic floor disorders. For example, neurostimulation systems have been developed with medical leads having discrete electrodes that are implanted on and near the sacral nerves. An implantable pulse generator drives the electrodes with an electrical signal to stimulate the sacral nerves, and thereby restore or control bodily functions affected by pelvic floor disorders. Several techniques of electrical neurostimulation may be used, including stimulation of nerve bundles within the sacrum. Such techniques may be particularly effective in alleviating sexual dysfunction or urinary incontinence. An example of an existing neurostimulation system for treatment of urinary urge incontinence is the implantable Interstim therapy system marketed by Medtronic, Inc. of Minneapolis, Minn.  
      Neurostimulation systems with multiple, self-contained neurostimulators also have been proposed. For example, U.S. Pat. No. 6,185,452 to Schulman et al. describes implantation of one or more miniature stimulators, referred to as microstimulators, with external electrodes for nerve or muscle stimulation. U.S. Pat. No. 6,650,943 to Whitehurst et al. describes implantation of microstimulators to treat erectile dysfunction. U.S. Pat. No. 6,735,474 to Loeb et al. describes a microstimulator system for treatment of urinary incontinence. Table 1 below lists documents that disclose various techniques for neurostimulation.  
                       TABLE 1                           Inventors/           Patent Number   Author   Title                  6,185,452   Schulman   Battery-powered patient implantable           et al.   device       6,449,512   Bojeva   Apparatus and method for treatment               of urological disorders using pro-               grammerless implantable pulse               generator system       6,507,755   Gozani et al.   Apparatus and method for stimu-               lating human tissue       6,571,128   Lebel et al.   Microprocessor controlled ambu-               latory medical apparatus with hand               held communication device       6,650,943   Whitehurst   Fully implantable neurostimulator           et al.   for cavernous nerve stimulation as               a therapy for erectile dysfunction               and other sexual dysfunction       6,735,474   Loeb et al.   Implantable stimulator system and               method for treatment of inconti-               nence and pain       US20040019369   Duncan et al.   Wireless functional electrical               stimulation system                  
 
      All documents listed in Table 1 above are hereby incorporated by reference herein in their respective entireties. As those of ordinary skill in the art will appreciate readily upon reading the Summary of the Invention, Detailed Description of the Preferred Embodiments and Claims set forth below, many of the devices and methods disclosed in the patents of Table 1 may be modified advantageously by using the techniques of the present invention.  
     SUMMARY  
      The invention is directed to a neurostimulation system and method that make use of an array of distributed electrical stimulators implanted at selected positions within a patient. Each stimulator is capable of independently delivering neurostimulation energy to a different site within a patient. A master controller communicates with the stimulators by wireless telemetry, and synchronizes the operation of the stimulators to deliver a desired mode of neurostimulation energy to the patient. The distributed stimulators function as “slave” stimulators that selectively stimulate particular nerve sites at particular times. The master controller may activate different sets of stimulators during the source of a physiological activity. The stimulators or the master controller may be responsive to one or more physiological sensing devices also implanted within the patient.  
      Various embodiments of the present invention provide solutions to one or more problems existing in the prior art with respect to prior art systems for neurostimulation. These problems include difficulties associated with effectively treating different phases or components of a physiological activity, such as sexual activity or urinary activity. Sexual activity, for example, generally involves two distinct phases, arousal and orgasm. Urinary activity involves retention and voiding phases. In each case, the particular neurostimulation characteristics, such as site, timing, or pulse parameters, necessary to support and transition between such phases may be markedly different. Hence, a neurostimulation system may focus on stimulation to achieve one functional phase, but neglect others, resulting in reduced therapeutic efficacy for the patient receiving the neurostimulation. In addition, a neurostimulation system may be directed to one component that drives a particular physiological activity, but ignore other components, such as the contributions of multiple nerve sites.  
      Various embodiments of the present invention are capable of solving at least some of the foregoing problems. When embodied in a system or method for neurostimulation, the invention includes features that support the selective application of neurostimulation to target particular nerve sites at particular times, which may enable delivery of neurostimulation targeted to specific functional phases and components of a physiological activity. In accordance with the invention, a plurality of distributed stimulators operate on a coordinated basis to deliver different modes of neurostimulation energy to particular nerve sites at particular times. The timing and location of the neurostimulation energy delivered by the stimulators are selected to support distinct phases of physiological activity in a progressive manner, or to target a combination of different components, such as different nerve sites. In some embodiments, a master controller or the individual stimulators are responsive to signals generated by one or more sensing devices. The sensing devices sense physiological parameters that may be useful in identifying the state or phase of activity, or a transition between different phases of activity, and hence a triggering event for adjustment of the neurostimulation mode.  
      In one embodiment, the invention provides a method for delivering neurostimulation therapy. The method may comprise applying first neurostimulation therapy to a patient via a first set of one or more implanted stimulators, and applying second neurostimulation therapy to the patient via a second set of one or more implanted stimulators. At least some of the stimulators in the first set are positioned at sites that are different from sites at which at least some of the stimulators in the second set are positioned.  
      In another embodiment, the invention provides a neurostimulation system comprising a first set of one or more implantable stimulators for delivery of a first neurostimulation therapy to a patient, and a second set of one or more implanted stimulators for delivery of a second neurostimulation therapy to the patient via a second set of one or more implanted stimulators. At least some of the stimulators in the first set are positioned at sites that are different from sites at which at least some of the stimulators in the second set are positioned. A controller selectively activates the first set of stimulators to deliver the first neurostimulation therapy and the second set of stimulators to deliver the second neurostimulation therapy.  
      In comparison to known implementations for neurostimulation, various embodiments of the present invention may provide one or more of advantages. By addressing distinct phases or components of physiological activity, for example, the invention may provide a more effective neurostimulation therapy. Instead of applying a single neurostimulation therapy, or a neurostimulation therapy targeted to a single phase or component of physiological activity, the invention can provide more effective coverage during the course of the physiological activity. For example, the invention may produce a composite neurostimulation therapy that targets different nerve sites, simultaneously or at different times, with the aid of an array of distributed stimulators. In addition, the invention may provide a more orderly transition between distinct phases of physiological activity, and more effective restoration and support of the distinct phases. As a further advantage, using distributed, wireless stimulators, multi-site stimulation can be achieved without the need to implant an excessive number of leads within the patient.  
      The above summary of the present invention is not intended to describe each embodiment or every embodiment of the present invention or each and every feature of the invention. Advantages and attainments, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.  
      The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     BRIEF DESCRIPTION OF DRAWINGS  
       FIG. 1  is a schematic diagram illustrating an implantable neurostimulation system for delivery of neurostimulation to treat pelvic floor disorders.  
       FIG. 2  is a schematic diagram illustrating coordinated control of different sets of implanted stimulators.  
       FIG. 3  is a schematic diagram illustrating an implantable stimulator.  
       FIG. 4  is a schematic diagram illustrating an implantable sensing device.  
       FIG. 5  is a schematic diagram illustrating an implantable module incorporating a stimulator and a sensor.  
       FIG. 6  is a block diagram illustrating components of an implantable stimulator.  
       FIG. 7  is a block diagram illustrating components of an implantable sensing device.  
       FIG. 8  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in response to patient input.  
       FIG. 9  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in response to a sensed physiological signal.  
       FIG. 10  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in response to a timing event.  
       FIG. 11  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in greater detail. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       FIG. 1  is a schematic diagram illustrating an implantable neurostimulation system  10  for delivery of neurostimulation to treat pelvic floor disorders. System  10  is configured to deliver neurostimulation therapies to a patient  12  via a plurality of distributed stimulators  14 A- 14 D (collectively stimulators  14 ) that may be capable of delivering neurostimulation energy independently of one another to different nerve sites. A master controller  16  communicates with stimulators  14  via wireless telemetry to control the operation of the stimulators in a selective, coordinated manner.  
      As further shown in  FIG. 1 , system  10  may include one or more distributed sensing devices  18  that sense physiological conditions within patient  12 . Sensing devices  18  communicate information representing physiological conditions to master controller  16  by wireless telemetry. Sensing devices  18  may be implanted within the pelvic floor region or elsewhere to sense physiological conditions pertinent to the control of neurostimulation therapy delivered by stimulators  14 .  
      Master controller  16  may be an external controller carried by patient  12 . Alternatively, master controller  16  may be integrated within one of stimulators  14  or sensing devices  18 . In this case, one of stimulators  14  acts as a “master” for one or more “slave” stimulators. Master controller  16  selectively activates and deactivates individual stimulators  14  or different sets of stimulators to deliver desired neurostimulation therapies to particular nerve sites at particular times. Master controller  16  may rely on information received from sensing devices  18  to selectively activate and deactivate stimulators  14 .  
      The physiological conditions sensed by sensors  18  may be useful in identifying a state or phase of physiological activity, or a transition between different phases of activity. Master controller  16  may use information received from sensing devices  18  as a triggering event for adjustment of neurostimulation. Adjustment may include selective activation or deactivation of different sets of neurostimulators  14  or adjustment of neurostimulation parameters such as electrode polarity, voltage or current amplitude, frequency, pulse width and duration. Master controller  16  may rely on other triggering events, such as user input or timing information, either individually or in combination with other triggering events.  
      The selective activation of different sets of stimulators  14  enables delivery of neurostimulation energy targeted to specific functional phases and components of a physiological activity. For example, the timing and location of the neurostimulation energy delivered by the stimulators  14  can be selected to support distinct phases of physiological activity in a progressive manner, or to target a combination of different components, such as different nerve sites, that may contribute to the progress of a particular physiological activity. In one embodiment, master controller  16  controls a first set of stimulators  14  to apply a first neurostimulation therapy to patient  12 , and controls a second set of stimulators to apply a second neurostimulation therapy to the patient. In this case, at least some of the stimulators  14  in the first set are positioned at sites that are different from sites at which at least some of the stimulators in the second set are positioned.  
      In the example of  FIG. 1 , stimulators  14  are implanted at different positions in proximity to sacrum  19  to access nerve sites within the pelvic floor region. In the example of  FIG. 1 , stimulators  14 A and  14 B are located proximate an upper region of sacrum  19 , while stimulators  14 C and  14 D are implanted proximate a lower region of sacrum  19 . Accordingly, stimulators  14 A and  14 B may stimulate a different set of nerves than stimulator  14 C and  14 D. As an example, stimulators  14 A and  14 B may target sacral nerves, while stimulators  14 C and  14 D target the pudendal nerve.  
      System  10  may be applied to deliver a variety of therapies formulated for different disorders or symptoms. Selected pelvic floor disorders such as sexual dysfunction or urinary incontinence will be described herein for purposes of illustration, although the invention is more broadly applicable to a variety of disorders that may respond to neurostimulation therapy. For example, distributed stimulators  14  within system  10  may cooperate to deliver therapy for alleviation of pelvic floor disorders such as urinary control disorders, fecal control disorders, interstitial cystitis, sexual dysfunction, and pelvic pain. Also, system  10  may be useful for spinal cord stimulation, providing sets of stimulators  14  that are oriented at different positions relative to the spinal cord.  
      As one example, system  10  may be applied to deliver therapy for relief of sexual dysfunction. The sexual dysfunction may take a variety of forms, including retrograde ejaculation, premature ejaculation, an ejaculation, and general inability to achieve arousal or orgasm. In an exemplary embodiment, system  10  delivers neurostimulation to the sacral nerves or other regions of the spinal cord known to have an effect on sexual function. Alternatively, or in addition, some stimulators  14  within system  10  may be configured to deliver neurostimulation to the pudendal nerve, the pelvic splanchnic nerve, or the cavernosa nerve in the penis.  
      A system for delivery of neurostimulation therapy for sexual dysfunction is disclosed in commonly assigned U.S. patent application Ser. No. 10/441,784, to Martin Gerber, filed May 19, 2003, entitled “TREATMENT OF SEXUAL DYSFUNCTION BY NEUROSTIMULATION,” the entire content of which is incorporated herein by reference. The system described in the above-referenced application may be adapted to use distributed stimulators  14  or other components of system  10 , as described herein. For sexual dysfunction, for example, system  10  may be adapted for delivery of different modes of neurostimulation to support the progress of, and transition between, distinct phases of sexual activity, such as arousal and orgasm. Selective activation of different sets of stimulators  14  positioned at different nerve sites may more effectively target components that support the particular phases.  
       FIG. 2  is a schematic diagram illustrating coordinated control of different sets of implanted stimulators  14 . In particular,  FIG. 2  shows a first set  21  of stimulators  14 , and a second set  23  of stimulators. In the example of  FIG. 2 , master controller  16  is integrated with stimulator  14 A, although the master controller may be a separately implanted device or an external device carried by the patient  12 . Integrated stimulator/master controller  14 A acts as both a stimulator and a “master” controller for other “slave” stimulators  14 . Stimulator  14 A, as master controller, may be responsive to information received from implanted sensing devices  18  to generate control signals. Also, stimulator  14 A may activate sensing devices  18  to obtain physiological information.  
      One or more stimulators  14  in system  10  are selectively implanted at positions designed to stimulate different C-fibers or sacral nerves at the second, third, and fourth sacral nerve positions, commonly referred to as S2, S3, and S4, respectively. Also, in some embodiments, one or more stimulators  14  may be implanted to deliver neurostimulation energy to the pudendal nerve. In this manner, system  10  may selectively stimulate the sacral nerves or pudendal nerve via different sets  21 ,  23  of stimulators  14 .  
      For purposes of example, first set  21  of stimulators  14  is implanted proximate selected sacral nerves, while second set  23  is implanted proximate the pudendal nerve. In operation, stimulator/master controller  14 A activates first set  21  of stimulators  14  with a first set of neurostimulation parameters to support the first phase of sexual activity. Then, stimulator/master controller  14 A deactivates the first set  21  of stimulators  14 , and activates second set  23  of stimulators with a second set of neurostimulation parameters to support the second phase of sexual activity.  
      Notably, in some embodiments, the first set  21  and second set  23  of stimulators  14  need not be mutually exclusive. For example, some stimulators  14  may be within both the first set and second set. Also, neurostimulation energy delivered by stimulators  14  in the first set may temporally or spatially overlap with neurostimulation energy delivered by stimulators in the second set. Moreover, the invention is not limited to delivery of stimulation via two sets of stimulators  14 , but may encompass two or more sets of distributed stimulators.  
      Again, stimulator/master controller  14 A activates first set  21  of stimulators  14  positioned proximate selected sacral nerves to initially deliver electrical stimulation with a first set of stimulation parameters selected to achieve a first phase of sexual activity. The first phase of sexual activity may involve sexual stimulation or arousal, which may be manifested by feelings of desire, penile erection in the case of male patients, or engorgement and lubrication in the case of female patients. The first set of stimulation parameters may specify the electrode polarity, waveform, voltage or current amplitude, pulse width, and frequency selected to support the first phase of sexual activity.  
      Upon receipt of a triggering event, which may include user input, timing information, or physiological information, stimulator/master controller  14 A then activates second set  23  of stimulators  14  to support a second phase of sexual activity. For example, stimulator/master controller  14 A activates stimulators  14  positioned proximate the pudendal nerve to cause the sexual activity to progress from the arousal phase, to a second phase, e.g., ejaculation or female orgasm. In addition to targeted stimulation of different nerve sites, the second set of distributed stimulators  14  may operate according to a second set of stimulation parameters appropriate to trigger the second phase of sexual activity.  
      Although the different sets of distributed stimulators  14  may target distinct phases of physiological activity, they also may work together to target different components that contribute to a single phase of activity. As an example, different sets of stimulators  14  may work together to simultaneously stimulate both the sacral nerves and the pudendal nerve to achieve a greater overall effect in restoring sexual function. In this sense, stimulation by second set  23  of stimulators  14  may be layered on top of stimulation provided by first set  21  of stimulators  14 . In either case, the distributed stimulators are selectively activated and used in a coordinated manner to provide either a multi-function stimulation generator or a multi-site stimulator.  
       FIG. 3  is a schematic diagram illustrating an implantable stimulator  14 . As shown in  FIG. 3 , stimulator  14  is preferably a self-contained module, mounted within its own housing  20 . Housing  20  may be constructed from any of a variety of biocompatible materials, such as titanium. As will be described, housing  20  may carry one or more electrodes to permit delivery of electrical stimulation, an implantable pulse generator (IPG), and a telemetry interface to transmit or receive control signals or sensor signals. Although stimulator  14  may include short leads with electrodes that extend from the housing for placement proximate to a desired tissue or nerve site, the electrodes preferably are integrated with the stimulator.  
      In the example of  FIG. 3 , housing  20  carries a pair of electrodes  22 ,  24 . Electrodes  22 ,  24  may be pads that are mounted on a particular surface of housing  20 , or ring electrodes that extend about the entire periphery of the housing. Each stimulator  14  includes an implantable pulse generator, and delivers neurostimulation therapy to patient  12  via electrodes  22 ,  24  in the form of electrical pulses generated by the implantable pulse generator. In some cases, housing  20  itself may form an active “can” electrode.  
      In alternative embodiments, stimulator  14  may include a single electrode for coordinated operation with an external reference electrode, such as a ground pad. Alternatively, a stimulator  14  may include two or more electrodes that form a bipolar or multi-polar stimulation arrangement. Hence, stimulators  14  may deliver neurostimulation energy independently of other stimulators or in a coordinated manner with other stimulators. In either case, the electrode or electrodes may be formed on the housing  20  of stimulator  14 .  
       FIG. 4  is a schematic diagram illustrating an implantable sensing device  18 . Like stimulator  14 , sensing device  18  preferably is a self-contained module having a housing  26 . Like housing  20 , housing  26  may be constructed from a biocompatible metal, such as titanium. A sensor  28  is mounted on or exposed by housing  26  to sense physiological conditions within patient  12  in the vicinity of the sensor.  FIG. 5  is a schematic diagram illustrating an implantable module  30  incorporating both a stimulator and a sensor. In the example of  FIG. 5 , a housing  29  carries both electrodes  22 ,  24  and a sensor  28  to provide stimulation and sensing functionality within a single module. Integration of stimulation and sensing in a single module may be desirable in some applications. In other applications, however, it will be advantageous to sense physiological conditions at a location remote from the site of stimulation, in order to assess the response of patient  12  to the stimulation.  
      Distributed sensing device  18  permit the sensing of physiological conditions at different locations during the course of physiological activity. As an example, various types of sensing devices  18  may be useful in indicating the progress of sexual activity. In response to signals transmitted by a sensing device  18 , a master controller  16  may selectively activate different sets  21 ,  23  of distributed stimulators  14 . The different sets  21 ,  23  of stimulators  14  deliver different neurostimulation therapies in distinct phases of sexual activity with neurostimulation parameters selected as appropriate to support those phases.  
      As an example, one or more physiological parameters may be sensed by sensing devices  18  during a first phase, e.g., arousal, in which neurostimulation is delivered using the first set  21  of stimulators  14 . The sensed physiological parameters are evaluated by sensing devices  18  or master controller  16  to determine that the patient is ready for progression to the next phase of sexual activity, e.g., orgasm. In this manner, master controller  16  obtains physiological parameters from different locations within the patient&#39;s body, such as within the genital area, via wireless telemetry by distributed sensing devices  18 .  
      Suitable physiological parameters include, without limitation, pressure, electromyographic potentials, blood pressure, blood flow, penile size, tumescence, or the like. Alternatively, as will be described, patient  12  may provide an explicit indication that he or she is ready for progression to the second phase of sexual activity. As a further alternative, a timer may be employed to indicate progression to the second phase of sexual activity following expiration of a predetermined period of time after initiation of the first phase of sexual activity.  
       FIG. 6  is a block diagram illustrating various components of an implantable stimulator  14  for use on a distributed basis within system  10  of  FIG. 1 . In the example of  FIG. 6 , a stimulator  14  includes a housing carrying a pair of electrodes  22 ,  24 , which can be referenced to each other to form a bipolar arrangement. Stimulator  14  further includes a processor, memory  34 , power source  36 , telemetry interface  38 , and therapy delivery circuit  40 . Electrodes  22 ,  24  are electrically coupled to a therapy delivery circuit  40 , which includes an implantable pulse generator to generate stimulation pulses. Power source  36  may be a battery, which may be non-rechargeable. Alternatively, the battery may be rechargeable with power delivered from an external charging device via an inductive power interface. As a further alternative, stimulator  14  may be inductively powered by an external device.  
      Processor  32  controls the implantable pulse generator within therapy delivery circuit  40  to deliver neurostimulation therapy according to selected stimulation parameters. Specifically, processor  32  controls therapy delivery circuit  40  to deliver electrical pulses with selected voltage or current amplitudes, pulse widths, frequencies, and durations specified by programs stored in memory  34 . In addition, processor  32  may control therapy delivery circuit  40  to deliver neurostimulation pulses via one or both of electrodes  22 ,  24  with selected polarities. In some embodiments, two or more electrodes may be provided on the housing of stimulator  14 .  
      Processor  32  may control therapy delivery circuit  40  to deliver each pulse according to a different program, thereby interleaving programs to simultaneously treat different symptoms or provide a combined therapeutic effect. For example, in addition to treatment of sexual dysfunction, stimulator  14  may be configured to deliver neurostimulation therapy to simultaneously treat pain or incontinence. Processor  32  may include a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other equivalent logic circuitry, or the like.  
      In some embodiments, memory  34  stores multiple sets of stimulation parameters that are available to be selected by patient  12  for delivery of neurostimulation therapy. For example, memory  34  may store stimulation parameters transmitted by an external clinician programmer. As described herein, the stimulation parameters may be formulated for treatment during distinct phases of sexual activity, such as a first phase involving arousal and a second phase involving orgasm. An external programmer may communicate with stimulator  14  by wireless telemetry to adjust neurostimulation delivered by the stimulator.  
      Memory  34  also stores program instructions that, when executed by processor  32 , cause stimulator  14  to deliver neurostimulation therapy. Memory  34  may include any volatile or non-volatile media, such as a RAM, ROM, NVRAM, EEPROM, flash memory, and the like, or any combination thereof. Accordingly, the invention also contemplates computer-readable media storing instructions to cause processor  32  to provide the functionality described herein.  
      Telemetry interface  38  supports wireless communication between stimulator  14  and master controller  16  for coordinated control with other stimulators, as well as communication with an external clinician programmer or patient programmer for programming of the stimulator. A handheld computing device (not shown) may be provided as a programmer to permit a clinician to program neurostimulation therapy into stimulators  14  for patient  12 , e.g., using input keys and a display. Using the external programmer, the clinician may specify neurostimulation parameters for use in the different phases of physiological activity by patient  12 . The external programmer supports radio frequency telemetry with stimulators  14  to download neurostimulation parameters and, optionally, upload operational or physiological data from the stimulators and sensing devices  18 . In this manner, a clinician may periodically interrogate system  10  to evaluate efficacy and, if necessary, modify the stimulation parameters.  
      The clinician programmer, in some embodiments, may be integrated with master controller  16 . More preferably, master controller  16  is integrated with an external patient programmer or one of stimulators  14 . Like the clinician programmer, a patient programmer can be provided as a handheld computing device. The patient programmer may include a display and input keys to allow patient  12  to interact with the patient programmer. In this manner, the patient programmer provides patient  12  with an interface for control of neurostimulation therapy by distributed stimulators  14 . For example, patient  12  may use the patient programmer to start, stop or adjust neurostimulation therapy. In particular, the patient programmer may permit patient  12  to adjust stimulation parameters such as amplitude, frequency, pulse width and duration, within an adjustment range specified by the clinician via a clinician programmer.  
      In some embodiments, the patient programmer may permit patient  12  to explicitly control transition of neurostimulation therapy from a first phase of activity to a second phase of activity. The patient programmer, whether integrated with master controller  16 , or not, supports radio frequency telemetry with stimulators  14  and sensing devices  18  to transmit neurostimulation instructions and receive sensed physiological conditions, and is sized for ease of portability, permitting patient  12  to carry the patient programmer.  
      Telemetry interface  38  may support wireless communication with one or more wireless sensing devices  18  that sense physiological signals and transmit the signals to stimulator  14 . Hence, stimulator  14  may be directly responsive to physiological signals generated by sensing devices  18 . Alternatively, master controller  16  may receive the physiological signals and transmit control signals to stimulator  14 . As described above, master controller  16  may be responsive to physiological signals sensed by physiological sensing devices  18  to control delivery of neurostimulation by one or more stimulators  14 . In response to detection of a particular physiological condition or level, master controller  16  may adjust the neurostimulation therapy delivered by stimulators  14 .  
      For example, master controller  16  may transition from a first set of stimulators  14  used to support a first phase of sexual activity to a different set of stimulators  14  used to support a second phase of sexual activity. Alternatively, master controller  16  may adjust the stimulation parameters associated with neurostimulation therapy delivered by a given set of stimulators  14  during a respective phase of sexual activity. In a first phase of sexual activity, sensing devices  18  may transmit signals indicative of the response of patient  12  to existing neurostimulation parameters. As an illustration, an implanted or external sensing device  18  may indicate a reduction in penile tumescence, in which case master controller  16  may increase the amplitude or frequency of neurostimulation pulses delivered by the first set of stimulators  14  in order to increase tumescence and maintain the first phase of sexual activity. In this manner, sensing devices  18  provide closed loop feedback for control of neurostimulation therapy.  
      Sensing device  18  also may sense one or more physiological parameters indicative of progression from the first phase of sexual activity to the second phase of sexual activity. For example, physiological sensing device  18  may sense changes in pressure, electromyographic potentials, or tumescence as an indication that patient  12  is ready for the second phase. In response, master controller  16  activates the second set of stimulators  14  to support transition to the second phase. Master controller  16  also may deactivate the first set of stimulators  14 , either before activation of the second set or after a predetermined period of time following activation of the second set. In some cases, first and second sets of stimulators  14  may be activated simultaneously, providing overlapping coverage. For example, the second set of stimulators  14  may be activated to provide an added layer of neurostimulation that triggers the second phase.  
       FIG. 7  is a block diagram illustrating various components of an implantable sensing device  18 . As shown in  FIG. 7 , sensing device  18  may include a processor  42 , memory  44 , power source  46 , telemetry interface  48  and physiological sensor  28 . Processor  42  and memory  44  may not be necessary in some embodiments. Instead, sensing device  18  may simply provide a sensor  28  and telemetry interface  48  equipped to transmit a raw, unprocessed sensor signal to master controller  16  and/or distributed stimulators  14 . In general, processor  42 , memory  44 , telemetry interface  48  and power source  46  may be constructed like similar components within stimulator  14 , as described above with reference to  FIG. 6 .  
      For treatment of sexual dysfunction, sensing device  18  can be implanted within the genital region of patient  12 , preferably without the need for a lead. For example, sensor  28  may be selected to sense pressure, blood flow, blood pressure, penile tumescence or the like. As further options, physiological sensor  18  may sense temperature, pressure changes, and frequency of pressure changes. Some sensing devices  18  may be deployed near the sacrum  19  to sense nerve responses.  
      Sensing devices  18  may be implanted within patient  12  or, in some cases, mounted externally. For example, in some embodiments, a penile tumescence, flow or pressure sensor may take the form of an external strain gauge ring mounted about the shaft of the penis. In various embodiments, sensing device  18  may take a variety of forms sufficient to sense desired physiological conditions including pressure sensors, flow sensors, temperature sensors, electromyographic sensors. Hence, in terms of structure, sensing device  18  may include strain gauge sensors, optical sensors, ultrasonic sensors, piezoelectric sensors, electrical sensors, or the like.  
      As one example, sensor  28  may take the form of a pressure sensor implanted within the penis or vagina of patient  12 . The pressure sensor monitors pressure levels and transmits a wireless signal indicative of the pressure levels to stimulators  14  or master controller  16  via wireless telemetry. The pressure sensor may monitor, for example, urethral pressure or blood pressure. Master controller  16  processes the pressure level signal and determines whether the pressure level exceeds or falls below an applicable predetermined threshold. Alternatively, master controller  16  analyzes changes in the pressure signal, and compares the rate of change of frequency of change to applicable thresholds.  
      Monitoring changes in pressure may permit system  10  to obtain a parameter indicative of a rhythm associated with sexual activity. As the pressure level, pressure slope or frequency of changes in pressure level exceeds an applicable threshold, master controller  16  transitions from a first set of stimulators  14  for a first sexual phase to a second set of stimulators  14  for a second sexual phase.  
      As another example, sensor  28  may take the form of an electromyographic (EMG) sensor that measures EMG potentials within the genital region, e.g., within the penis or clitoris. Physiological sensing device  18 , or sense electrodes associated with sensor  28 , may be implanted within the genital region. In this case, master controller  16 , or distributed sensing devices  18 , receives EMG signals from physiological sensing device  18  via wireless communication, and processes the signals to identify EMG levels, slopes, or frequency of EMG changes that exceed applicable thresholds.  
      Physiological sensing device  18 , according to another example, may take the form of a blood flow sensor that monitors increased blood flow into the male or female genital region, i.e., tumescence. In this case, physiological sensing device  18  can be implanted in the penis or vagina, and may sense tumescence by sensing impedance changes or pressure changes. For pressure changes, for example, a strain gauge may be fitted to the genital region, either over or under the skin. Impedance measurements on the skin surface also may be indicative of lubrication. Master controller  16  receives the tumescence signals from physiological sensing device  18 , via a lead or wireless communication, and processes the signals to identify tumescence levels, slopes, or frequency of change that exceed applicable thresholds. When the threshold is exceeded, system  10  transitions between first and second sets of stimulators  14 .  
      For urinary incontinence applications, sensing devices  18  may be implanted to sense bladder pressure, bladder contractile force, urine level, urethral pressure, urethral flow, urine presence within the urethra or other parameters indicating the state of bladder function. In a first phase of urinary activity, master controller  16  may activate a first set of stimulators  14  to cause bladder contraction and urinary voiding, and then activate a second set of stimulators  14  to cause bladder relaxation for retention of urine. Alternatively, a first set of stimulators  14  may cause urinary sphincter contraction to retain urine, while a second set of stimulators  14  causes sphincter relaxation to permit urine flow. In either case, sensing devices  18  may provide feedback to master controller  16  for maintenance of, or transition between, such phases of urinary activity.  
      Master controller  16 , stimulators  14  and sensing devices  18  communicate via radio frequency (RF) telemetry. For example, RF telemetry may be accomplished using any of a variety of RF communication techniques and protocols, such as proprietary RF communication protocols used in the medical device arts, as well as standardized RF communication protocols in more general use, such as the various IEEE 802.11 protocols or the Bluetooth protocol. Master controller  16 , stimulators  14  and sensing devices  18  are equipped with appropriate modulation, demodulation, amplification, filtering and antenna circuitry to support wireless telemetry.  
      In general, to facilitate collision-free, two-way communication, master controller  16  may assign time slots, frequency channels, or spreading codes to sensing devices  18 . In this manner, sensing devices  18  can transmit sensor signals to master controller  16  without contention. Master controller  16  may statically assign time slots or channels to sensing devices  18  or change the assignments dynamically. For example, some sensing devices  18  may be less important during one phase of physiological activity, and therefore may be afforded less bandwidth for transmissions, whereas other sensing devices may receive greater bandwidth. Dynamic assignment of bandwidth may also permit conservation of battery resources during periods in which frequent transmission of sensor signals would be wasteful.  
      To activate different sets  21 ,  23  of stimulators  14  or sensing device  18 , master controller  16  may employ an addressing scheme. For example, each stimulator  14  or sensors  18  may be assigned a unique address so that signals transmitted by the master controller  16  and intended for a particular stimulator or sensing device can be identified by the respective device. In other words, a particular stimulator  14  or sensing device  18  is responsive to control signals carrying the appropriate address or identifier.  
      In addition, to facilitate activation of a set of multiple stimulators  14  or sensing devices  18 , master controller  16  may employ a group addressing scheme. For example, a set  21 ,  23  of stimulators  14  may be responsive to a group address identifier, which signifies that each stimulator sharing the group identifier should respond to the control signal. A similar approach may be used for sensing devices  18 , if multiple sensing devices are to be activated in groups. In each case, a unique address or group address may be transmitted with a control signal, e.g., within a packet header or other administrative section of a transmission.  
       FIG. 8  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators  14  in response to patient input. In the example of  FIG. 8 , master controller  16  activates a first set  21  of stimulators  14  to support a first phase of physiological activity ( 50 ), such as a first phase of sexual activity. The first phase may be initiated in response to user input requesting that master controller  16  activate neruostimulation. Master controller  16 , which may be embodied within an external programmer or integrated with a stimulator  14  or sensing device  18 , monitors user input ( 52 ). If the user input indicates a desire to transition form the first phase of activity to a second phase of physiological activity ( 54 ), master controller  16  activates a second set of stimulators  14  to support the second phase of physiological activity ( 56 ).  
      In this manner, system  10  is responsive to an explicit indication by patient  12  that he or she is ready for progression to the second phase of activity. The user input may be provided by actuating an input device associated with an external programmer, which may or may not incorporate master controller  16 . For transition from the first phase to the second phase, master controller  16  also may selectively apply different stimulation parameters via distributed stimulators  14 . The first set of stimulators  14  may remain activated with the second set of stimulators, with the same or different stimulation parameters. Alternatively, the first set of stimulators  14  may be deactivated upon or shortly following activation of the second set of stimulators.  
       FIG. 9  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in response to a sensed physiological signal. The method of  FIG. 9  involves monitoring a physiological signal during the course of physiological activity via one or more distributed sensing devices  18  and delivering stimulation via one or more distributed stimulators  14  in response to the sensed signal. As shown in  FIG. 9 , master controller  16  a first set  21  of stimulators  14  to support a first phase of physiological activity ( 58 ), and monitors a physiological signal transmitted by one or more of sensing devices  18  ( 60 ). If the sensed signal exceeds an applicable threshold ( 62 ), or otherwise satisfies a predetermined set of criteria, master controller  16  activates a second set of stimulators  14  to support a second phase of activity ( 64 ).  
      Master controller  16  may be responsive to a level of the sensed signal, or some other characteristic of the signal, such as a frequency, average or trend. In the example of sexual dysfunction, the signal may represent a variety of parameters such as pressure, blood flow, blood pressure, penile tumescence or the like. Master controller  16  may receive a raw signal and process the signal for comparison to a threshold or other criteria. Alternatively, sensing devices  18  may pre-process the signal for local comparison to a threshold or other criteria, and transmit a trigger signal to master controller  16 .  
       FIG. 10  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in response to a timing event. In the example of  FIG. 10 , master controller  16  activates a first set  21  of stimulators  14  to support a first phase of physical activity  66 ), and then activates a timer ( 68 ). When the timer reaches a predetermined limit ( 70 ), master controller  16  activates a second set  23  of stimulators  14  to support a second phase of activity ( 72 ). In this manner, master controller  16  applies a time limit between the first phase and the transition to the second phase. The timing information may be combined with other trigger events. For example, master controller  16  may consider both the time limit and physiological signals sensed by sensing device  18 . Also, user input may override control based on a time limit or physiological signals to permit the user to transition between the phases at an earlier or later time.  
      In the case of sexual activity, master controller  16  applies a time limit between arousal and orgasm. For urinary activity, master controller  16  may apply a time limit between the start of a voiding event and the end of a voiding event. For example, first set  21  of stimulators  14  may initially trigger relaxation of the bladder sphincter and/or contraction of the bladder muscle, and the second set  23  may trigger contraction of the bladder sphincter and/or relaxation of the bladder muscle upon expiration of a time limit.  
      For urinary incontinence, neurostimulation for different phases of a voiding event may be accompanied by a substantially full-time neurostimulation program that counteracts bladder contraction or sphincter relaxation to avoid incontinence outside of planning voiding events. When the patient wishes to void, he may provide user input requesting that master controller  16  activate neurostimulation to permit voiding.  
      The time limit for sexual activity or voiding may be selected to correspond to an average time ordinarily associated with normal transition between the distinct phases of activity, or a time unique to a particular patient  12 . For example, the predetermined period of time may be selected by a clinician according to a patient request. Alternatively, in some embodiments, patient  12  may be permitted to adjust the time using a patient programmer.  
       FIG. 11  is a flow diagram illustrating a method for delivering neurostimulation therapies using first and second sets of stimulators in greater detail. In the example of  FIG. 11 , master controller  16  controls not only selection of different set of stimulators  14  to transition between different phases, but also adjustment of neurostimulation parameters within a given phase. In addition,  FIG. 11  depicts the transmission of group activation commands to activate a set of stimulators  14  simultaneously.  
      As shown in  FIG. 11 , master controller  16  initially transmits a group activation command to activate a first set of stimulators  14  ( 74 ) to deliver neurostimulation energy. During the course of the first phase, sensing devices  18  sense physiological conditions ( 76 ) and transmit corresponding signals to master controller  16 . If the signals do not indicate the need for transition to a second phase ( 78 ), master controller  16  determines whether the signals indicate the need for an adjustment to the neurostimulation parameters within the first phase ( 80 ). If so, master controller  16  adjusts one or more neurostimulation parameters ( 82 ) and transmits the adjustments to the first set  21  of stimulators  14  in a group activation command ( 74 ).  
      The sensing of physiological conditions and adjustment of neurostimulation parameters continues on an iterative, closed loop basis until a transition to the second phase is necessary ( 78 ), e.g., in response to a sensed physiological condition or in response to another trigger event such as expiration of a time limit or an explicit user command. For transition to the second phase, master controller  16  transmits a group activation command ( 84 ) to activate a second set  23  of stimulators  14 . Master controller  16  then initiates a closed loop adjustment process for adjustment of the neurostimulation parameters delivered by the second set of stimulators  14 , until the physiological activity is complete.  
      For example, during the course of the second phase, sensing devices  18  sense physiological conditions ( 86 ) and transmit corresponding signals to master controller  16 . If the signals do not indicate completion of the second phase ( 88 ), master controller  16  determines whether the signals indicate the need for an adjustment to the neurostimulation parameters within the second phase ( 90 ), e.g., to achieve completion. If so, master controller  16  adjusts one or more neurostimulation parameters ( 92 ) and transmits the adjustments to the second set  23  of stimulators  14  in another group activation command ( 84 ).  
      As an illustration, for sexual dysfunction, master controller  16  controls a first set  21  of stimulators  14  to deliver neurostimulation pulses to selected sacral nerves to support a first phase of sexual activity, i.e., arousal. The neurostimulation pulses delivered by the first set  21  of stimulators  14  may have a frequency in the range of approximately 10 to 150 Hz, and more preferably approximately 20 to 60 Hz. Each pulse for the first phase may have an voltage amplitude in the range of approximately 0.5 to 10 volts, and more preferably approximately 2 to 5 volts, and a pulse width in the range of approximately 100 to 400 microseconds, and more preferably approximately 200 to 300 microseconds. The duration of the first phase neurostimulation will depend on the detected transition to the second phase, but typically may be on the order of approximately 2 to 30 minutes. Master controller  16  or stimulators  14  may specify multiple settings, however, such that there are different sets of parameters for the first phase for different times of the day, different environments, and the like.  
      Upon transition to the second phase, master controller  16  controls a second set of stimulators  14  to deliver neurostimulation pulses to a different location within the pelvic floor region. In particular, at least some of the stimulators  14  in the second set  23  are positioned at sites that are different from sites at which at least some of the stimulators  14  in the first set  21  are positioned. For example, one or more of stimulators  14  in the second set  23  may be placed near the pudendal nerve. The pulses delivered by simulators  14  in the second set  23  may have a frequency in the range of approximately 1 to 5 Hz, or in the range of approximately 25 to 35 Hz. Each pulse for the second phase may have an amplitude in the range of approximately 1 to 10 volts, and more preferably approximately 2 to 5 volts, and a pulse width in the range of approximately 100 to 700 microseconds, and more preferably approximately 200 to 300 microseconds. The duration of the second phase neurostimulation delivered by the second set  23  of stimulators  14  may be on the order of approximately 1 to 5 minutes. Like the first phase neurostimulation parameters, there may be multiple settings for the second phase parameters.  
      The preceding specific embodiments are illustrative of the practice of the invention. It is to be understood, therefore, that other expedients known to those skilled in the art or disclosed herein may be employed without departing from the invention or the scope of the claims. For example, the present invention is not limited to the particular factors of sexual dysfunction described herein. In addition, the present invention further includes within its scope methods of making and using systems for neurostimulation, as described herein. Importantly, although application of the invention to sexual dysfunction and urinary incontinence has been described herein, the invention may be broadly applicable to a variety of other disorders such as chronic pain, urinary or fecal incontinence, interstitial cystitis, and pelvic pain, to name a few. When applied to nerves found to stimulate sexual activity, the invention may be applied to sacral nerves, the pudendal nerve, the pelvic splanchnic nerve, or the cavernosa nerve in the penis. In addition, although wireless communication is contemplated between distributed stimulators  14 , master controller  16 , and sensing devices  18 , in some embodiments, communication may be accomplished, at least in part, by wired connections.  
      In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures. Thus, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface, in the environment of fastening wooden parts a nail and a screw are equivalent structures.  
      Many embodiments of the invention have been described. Various modifications may be made without departing from the scope of the claims. These and other embodiments are within the scope of the following claims.