WO2024207066A1

WO2024207066A1 - Diagnosis and treatment of neuropathic pain

Info

Publication number: WO2024207066A1
Application number: PCT/AU2024/050319
Authority: WO
Inventors: David Martin Mugan
Original assignee: Saluda Medical Pty Limited
Priority date: 2023-04-04
Filing date: 2024-04-04
Publication date: 2024-10-10

Abstract

Disclosed is a method of measuring neuropathic pain associated with an affected dermatome of a patient. The method comprises: measuring at least one lateral characteristic value of at least one action potential laterally to a dorsal root ganglion (DRG) of sensory afferents from the affected dermatome; measuring at least one medial characteristic value of at least one action potential medially to the DRG of sensory afferents from the affected dermatome; measuring an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value. Also disclosed are devices and systems for carrying out the disclosed methods.

Description

DIAGNOSIS AND TREATMENT OF NEUROPATHIC PAIN

TECHNICAL FIELD

[0001] The present invention relates to neuropathic pain and in particular to devices and methods for diagnosing and treating neuropathic pain using sensed neural signals.

BACKGROUND OF THE INVENTION

[0002] There are a range of situations in which it is desirable to apply neural stimuli in order to alter neural function, a process known as neuromodulation. For example, neuromodulation is used to treat a variety of disorders including chronic neuropathic pain, Parkinson’s disease, and migraine. A neuromodulation device applies an electrical pulse (stimulus) to neural tissue (fibres, or neurons) in order to generate a therapeutic effect. In general, the electrical stimulus generated by a neuromodulation device evokes a neural response known as an action potential in a neural fibre which then has either an inhibitory or excitatory effect. Inhibitory effects can be used to modulate an undesired process such as the transmission of pain, or excitatory effects may be used to cause a desired effect such as the contraction of a muscle.

[0003] When used to relieve neuropathic pain originating in the trunk and limbs, the electrical pulse is applied to the dorsal column (DC) of the spinal cord, a procedure referred to as spinal cord stimulation (SCS). Such a device typically comprises an implanted electrical pulse generator, and a power source such as a battery that may be transcutaneously rechargeable by wireless means, such as inductive transfer. An electrode array is connected to the pulse generator, and is implanted adjacent the target neural fibre(s) in the spinal cord, typically in the dorsal epidural space above the dorsal column. An electrical pulse of sufficient intensity applied to the target neural fibres by a stimulus electrode causes the depolarisation of neurons in the fibres, which in turn generates an action potential in the fibres. Action potentials propagate along the fibres in an orthodromic direction (in afferent fibres this means towards the head, or rostral) and in an antidromic direction (in afferent fibres this means towards the cauda, or caudal) directions. Action potentials propagating along A|3 (A-beta) fibres being stimulated in this way may inhibit the transmission of pain from a region of the body innervated by the target neural fibres (the dermatome) to the brain. To sustain the pain relief effects, stimuli are applied repeatedly, for example at a frequency in the range of 30 Hz - 100 Hz.

[0004] For effective and comfortable neuromodulation, it is necessary to maintain stimulus intensity above a recruitment threshold. Stimuli below the recruitment threshold will fail to recruit sufficient neurons to generate action potentials with a therapeutic effect. In some neuromodulation applications, response from a single class of fibre is desired, but the stimulus waveforms employed can evoke action potentials in other classes of fibres which cause unwanted side effects. In pain relief, it is therefore desirable to apply stimuli with intensity below a discomfort threshold, above which uncomfortable or painful percepts arise due to over-recruitment of Ap fibres or recruitment of undesired fibre classes. When recruitment is too large, A[3 fibres produce uncomfortable sensations. Stimulation at high intensity may even recruit A5 (A-delta) fibres, which are sensory nerve fibres associated with acute pain, cold and heat sensation. It is therefore desirable to maintain stimulus intensity within a therapeutic range between the recruitment threshold and the discomfort threshold.

[0005] The task of maintaining appropriate neural recruitment is made more difficult by electrode migration (change in position over time) or postural changes of the implant recipient (patient), either of which can significantly alter the neural recruitment arising from a given stimulus, and therefore the therapeutic range. There is room in the epidural space for the electrode array to move, and such array movement from migration or posture change alters the electrode-to-cord distance and thus the recruitment efficacy of a given stimulus. Moreover, the spinal cord itself can move within the cerebrospinal fluid (CSF) with respect to the dura. During postural changes, the amount of CSF or the distance between the spinal cord and the electrode can change significantly. This effect is so large that postural changes alone can cause a previously comfortable and effective stimulus regime to become either ineffectual or painful.

[0006] Attempts have been made to address such problems by way of feedback or closed-loop control, such as using the methods set forth in International Patent Publication No. WO2012/155188 by the present applicant. Feedback control seeks to compensate for relative nerve / electrode movement by controlling the intensity of the delivered stimuli so as to maintain neural recruitment at or near a target value. The intensity of a neural response evoked by a stimulus may be used as a feedback variable representative of the amount of neural recruitment. A signal representative of the neural response may be sensed by a measurement electrode in electrical communication with the recruited neural fibres, and processed to obtain the feedback variable. Based on the response intensity, the intensity of the applied stimulus may be adjusted to bring the response intensity closer to the target value.

[0007] It is therefore desirable to accurately measure the intensity and other characteristics of a neural response evoked by the stimulus. The action potentials generated by the depolarisation of a large number of fibres by a stimulus sum to form a measurable signal known as an evoked compound action potential (ECAP). Accordingly, an ECAP is the sum of responses from a large number of single fibre action potentials. The ECAP generated from the depolarisation of a group of similar fibres may be measured at a measurement electrode as a positive peak potential, then a negative peak, followed by a second positive peak. This morphology is caused by the region of activation passing the measurement electrode as the action potentials propagate along the individual fibres.

[0008] Approaches proposed for obtaining a neural response measurement are described by the present applicant in International Patent Publication No. WO2012/155183, the content of which is incorporated herein by reference.

[0009] Neuromodulation by implantable devices is an invasive therapy, and therefore before undertaking it, clinicians and patients need a degree of confidence that it will have some efficacy. However, neuropathic pain is notoriously difficult to differentially diagnose from chronic nociceptive or inflammatory pain, on which neuromodulation as described above is ineffective, but this is an important step in determining whether neuromodulation is likely to be an effective therapy.

[0010] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

[0011] Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0012] In this specification, a statement that an element may be “at least one of’ a list of options is to be understood to mean that the element may be any one of the listed options, or may be any combination of two or more of the listed options. SUMMARY OF THE INVENTION

[0013] According to a first aspect of the present technology, there is provided a method of measuring neuropathic pain associated with an affected dermatome of a patient, the method comprising: measuring at least one lateral characteristic value of at least one action potential lateral to a dorsal root ganglion (DRG) of sensory afferents from the affected dermatome; measuring at least one medial characteristic value of at least one action potential medial to the DRG of sensory afferents from the affected dermatome; measuring an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generating a measure of neuropathic pain from the DRG effect measure.

[0014] According to a second aspect of the present technology, there is provided a device for measuring neuropathic pain associated with an affected dermatome of a patient, the device comprising: measurement circuitry configured to: capture at least one lateral signal window from at least one signal sensed laterally to a dorsal root ganglion (DRG) of sensory afferents from the affected dermatome, the at least one signal sensed via one or more measurement electrodes located laterally to the DRG, and capture at least one medial signal window from at least one signal sensed medially to the DRG via one or more measurement electrodes located medially to the DRG; and a control unit configured to: measure, in the at least one lateral signal window, at least one lateral characteristic value of at least one action potential lateral to the DRG; measure, in the at least one medial signal window, at least one medial characteristic value of at least one action potential medial to the DRG; measure an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generate a measure of neuropathic pain from the DRG effect measure.

[0015] According to a third aspect of the present technology, there is provided a system comprising: measurement circuitry configured to: capture at least one lateral signal window from at least one signal sensed laterally to a dorsal root ganglion (DRG) of sensory afferents from an affected dermatome, the at least one signal sensed via one or more measurement electrodes located laterally to the DRG, and capture at least one medial signal window from at least one signal sensed medially to the DRG via one or more measurement electrodes located medially to the DRG; and a processor configured to: measure, in the at least one lateral signal window, at least one lateral characteristic value of at least one action potential lateral to the DRG; measure, in the at least one medial signal window, at least one medial characteristic value of at least one action potential medial to the DRG; measure an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generate a measure of neuropathic pain from the DRG effect measure.

[0016] In some embodiments of the invention, the at least one action potential is an evoked compound action potential (ECAP).

[0017] Some embodiments of the invention may further comprise delivering stimuli laterally to the DRG so as to evoke the ECAP(s). For example the delivering may comprise delivering electrical stimuli to the sensory afferents proximal to the DRG. Additionally or alternatively, the delivering may comprise delivering peripheral stimuli at the affected dermatome. The delivering may comprise delivering electrical stimuli transcutaneously.

[0018] In some embodiments of the invention each measured characteristic value is action potential amplitude. Measuring the effect of the DRG may comprise: constructing a medial histogram of a plurality of measured medial amplitudes; constructing a lateral histogram of a plurality of measured lateral amplitudes; and computing the effect of the DRG as a ratio between a representative value of the medial histogram and a representative value of the lateral histogram.

[0019] In some embodiments, the measured medial characteristic value and the measured lateral characteristic value may comprise a number of measurable medial and lateral action potentials respectively. [0020] Measuring the effect of the DRG may in some embodiments comprise computing the effect of the DRG as a ratio between the number of measurable medial action potentials and the number of measurable lateral action potentials. In some embodiments generating a measure of neuropathic pain may further comprise determining whether the measured DRG effect exceeds a threshold. Such embodiments may further comprise communicating, based on the determining, an indicator that pain associated with the affected dermatome is neuropathic.

[0021] The measure of neuropathic pain in some embodiments may be a non-binary measure of severity of neuropathic pain. The measure of severity may be a pre-therapy measure of severity, and the method may further comprise: applying a therapy for the neuropathic pain; repeating the measuring of a severity of neuropathic pain to obtain a post-therapy measure of severity of neuropathic pain; and computing a measure of efficacy of the therapy from the pre-therapy measure of severity of neuropathic pain and the post-therapy measure of severity of neuropathic pain.

[0022] Some embodiments of the device and system may further comprise a plurality of electrodes including the one or more measurement electrodes located laterally to the DRG, and the one or more measurement electrodes located medially to the DRG.

[0023] Some embodiments of the device and system may further comprise an external device in communication with the measurement circuitry. The processor may be part of the external device.

[0024] In some embodiments of the device and system, the measurement circuitry and the processor may form part of an integrated diagnostic device.

[0025] References herein to estimation, determination, comparison and the like are to be understood as referring to an automated process carried out on data by a processor operating to execute a predefined procedure suitable to effect the described estimation, determination or comparison step(s). The technology disclosed herein may be implemented in hardware (e.g., using digital signal processors, application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs)), or in software (e.g., using instructions tangibly stored on non-transitory computer-readable media for causing a data processing system to perform the steps described herein), or in a combination of hardware and software. The disclosed technology can also be implemented as computer-readable code on a computer-readable medium. The computer-readable medium can include any data storage device that can store data which can thereafter be read by a computer system. Examples of the computer-readable medium include read-only memory ("ROM"), random-access memory ("RAM"), magnetic tape, optical data storage devices, flash storage devices, or any other suitable storage devices. The computer-readable medium can also be distributed over network-coupled computer systems so that the computer-readable code is stored or executed in a distributed fashion.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Notwithstanding any other implementations which may fall within the scope of the present invention, implementations of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

Fig. 1 schematically illustrates an implanted spinal cord stimulator, according to one implementation of the present technology;

Fig. 2 is a block diagram of the stimulator of Fig. 1;

Fig. 3 is a schematic illustrating interaction of the implanted stimulator of Fig. 1 with a nerve;

Fig. 4 illustrates an idealised activation plot for one posture of a patient undergoing neural stimulation;

Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system, according to one implementation of the present technology;

Fig. 6 illustrates the typical form of an electrically evoked compound action potential (ECAP) of a healthy subj ect;

Fig. 7 is a block diagram of a neural stimulation therapy system including the implanted stimulator of Fig. 1 according to one implementation of the present technology;

Fig. 8A is a simplified representation of the neuroanatomy of the spinal cord, and Fig. 8B illustrates measurement of DRG amplification from such anatomy; and

Fig. 9 is a flow chart illustrating a method of diagnosing neuropathic pain according to an implementation of the present technology.

DETAILED DESCRIPTION OF THE PRESENT TECHNOLOGY

[0027] Disclosed herein are devices and methods for diagnosing neuropathic pain, as opposed to nociceptive pain. Devices and methods according to the present disclosure sense neural signals (action potentials, e.g. evoked compound action potentials) from the periphery entering (lateral to) and emerging from (medial to) the dorsal root ganglion. The medial neural signals are compared with the lateral neural signals to measure an effect on the neural signals of the dorsal root ganglion (DRG). If significant amplification has taken place, as quantified by the effect of the DRG on the neural signals, neuropathic pain is indicated. Once neuropathic pain is diagnosed, neuromodulation devices according to the present disclosure may be deployed to deliver neural stimulation therapy for the neuropathic pain. The DRG effect measure may be derived prior to neural stimulation as a diagnostic procedure, or during lead implantation, or during programming of the neural stimulation therapy to obtain suitable lead placement and therapy program parameters. The DRG effect measure may be used to derive a measure of the efficacy of neural stimulation therapy for the neuropathic pain.

[0028] Fig. 1 schematically illustrates an implanted spinal cord stimulator 100 in a patient 108, according to one implementation of the present technology. Stimulator 100 comprises an electronics module 110 housed within a conductive case, implanted at a suitable location. In one implementation, stimulator 100 is implanted in the patient’s lower abdominal area or posterior superior gluteal region. In other implementations, the electronics module 110 is implanted in other locations, such as in a flank or sub-clavicularly. In yet other implementations, the electronics module 110 is external to the patient 108. Stimulator 100 further comprises an electrode array 150 implanted within the epidural space and connected to the module 110 by a suitable lead. The electrode array 150 may comprise one or more electrodes such as electrode pads on a paddle lead, circular (e.g., ring) electrodes surrounding the body of the lead, conformable electrodes, cuff electrodes, segmented electrodes, or any other type of electrodes capable of forming unipolar, bipolar or multipolar electrode configurations for stimulation and measurement. The electrodes may pierce or affix directly to the tissue itself.

[0029] Numerous aspects of the operation of the stimulator 100 may be programmable by an external computing device 192, which may be operable by a user such as a clinician or the patient 108. Moreover, stimulator 100 serves a data gathering role, with gathered data being communicated to external device 192 via a transcutaneous communications channel 190. Communications channel 190 may be active on a substantially continuous basis, at periodic intervals, at non-periodic intervals, or upon request from the external device 192. External device 192 may thus provide a clinical interface configured to program the stimulator 100 and recover data stored on the stimulator 100. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the clinical interface.

[0030] Fig. 2 is a block diagram of the stimulator 100. Electronics module 110 contains a battery 112 and a telemetry module 114. In implementations of the present technology, any suitable type of transcutaneous communications channel 190, such as infrared (IR), radiofrequency (RF), capacitive or inductive transfer, may be used by telemetry module 114 to transfer power or data to and from the electronics module 110 via communications channel 190. Module controller 116 has an associated memory 118 storing one or more of clinical data 120, clinical settings 121, control programs 122, and the like. Controller 116 is configured by control programs 122, sometimes referred to as firmware, to control a pulse generator 124 to generate stimuli, such as in the form of electrical pulses, in accordance with the clinical settings 121. Electrode selection module 126 switches the generated pulses to the selected electrode(s) of electrode array 150, for delivery of the pulses to the tissue surrounding the selected electrode(s). Measurement circuitry 128, which may comprise an amplifier or an analog-to-digital converter (ADC), is configured to process signals comprising neural responses sensed at measurement electrode(s) of the electrode array 150 as selected by electrode selection module 126.

[0031] Fig. 3 is a schematic illustrating interaction of the stimulator 100 with a nerve 180 in the patient 108. In the implementation illustrated in Fig. 3 the nerve 180 may be located in the spinal cord, however in alternative implementations the stimulator 100 may be positioned adjacent any desired neural tissue including a peripheral nerve, visceral nerve, parasympathetic nerve or a brain structure. Electrode selection module 126 selects a stimulus electrode 2 of electrode array 150 through which to deliver a pulse from the pulse generator 124 to surrounding tissue including nerve 180. A pulse may comprise one or more phases, e.g. a monophasic pulse comprises one phase, and a biphasic stimulus pulse 160 comprises two phases. Electrode selection module 126 also selects a return electrode 4 of the electrode array 150 for stimulus current return in each phase, to maintain a zero net charge transfer. An electrode may act as both a stimulus electrode and a return electrode over a complete multiphasic stimulus pulse. The use of two electrodes in this manner for delivering and returning current in each stimulus phase is referred to as bipolar stimulation. Alternative implementations may apply other forms of bipolar stimulation, or may use a greater number of stimulus or return electrodes. By contrast, in monopolar stimulation, current is returned through the conductive case of the stimulator 100, which may therefore be configured and function as an electrode though it is not physically part of the electrode array 150. The set of stimulus electrodes and return electrodes is referred to as the stimulus electrode configuration. Electrode selection module 126 is illustrated as connecting to a ground 130 of the pulse generator 124 to enable stimulus current return via the return electrode 4. However, other connections for current return may be used in other implementations. [0032] Delivery of an appropriate stimulus via electrodes 2 and 4 to the nerve 180 evokes a neural response 170 comprising an evoked compound action potential (ECAP) which will propagate along the nerve 180 as illustrated at a rate known as the conduction velocity. The ECAP may be evoked for therapeutic purposes, which in the case of a spinal cord stimulator for chronic pain may be to create paraesthesia at a desired location. To this end, the electrodes 2 and 4 are used to deliver stimuli periodically at any therapeutically suitable frequency, for example 30 Hz, although other frequencies may be used including frequencies as high as the kHz range. In alternative implementations, stimuli may be delivered in a non-periodic manner such as in bursts, or sporadically, as appropriate for the patient 108. To program the stimulator 100 to the patient 108, a clinician may cause the stimulator 100 to deliver stimuli of various configurations which seek to produce a sensation that is experienced by the user as paraesthesia. When a stimulus electrode configuration is found which evokes paraesthesia in a location and of a size which is congruent with the area of the patient’s body affected by pain and of a quality that is comfortable for the patient, the clinician or the patient nominates that configuration for ongoing use. The therapy parameters may be loaded into the memory 118 of the stimulator 100 as the clinical settings 121.

[0033] Fig. 6 illustrates the typical form of an ECAP 600 of a healthy subject, as recorded at a single measurement electrode referenced to the system ground 130. The shape and duration of the single- ended ECAP 600 shown in Fig. 6 is predictable because it is a result of the ion currents produced by the ensemble of fibres depolarising and generating action potentials (APs) in response to stimulation. The evoked action potentials (EAPs) generated synchronously among a large number of fibres sum to form the ECAP 600. The ECAP 600 generated from the synchronous depolarisation of a group of similar fibres comprises a positive peak Pl, then a negative peak Nl, followed by a second positive peak P2. This shape is caused by the region of activation passing the measurement electrode as the action potentials propagate along the individual fibres.

[0034] The ECAP may be recorded differentially using two measurement electrodes, as illustrated in Fig. 3. Differential ECAP measurements are less subject to common-mode noise on the surrounding tissue than single-ended ECAP measurements. Depending on the polarity of recording, a differential ECAP may take an inverse form to that shown in Fig. 6, i.e. a form having two negative peaks Nl and N2, and one positive peak Pl. Alternatively, depending on the distance between the two measurement electrodes, a differential ECAP may resemble the time derivative of the ECAP 600, or more generally the difference between the ECAP 600 and a time-delayed copy thereof. [0035] The ECAP 600 may be characterised by any suitable character! stic(s) of which some are indicated in Fig. 6. The amplitude of the positive peakPl is A and occurs at time Tpi. The amplitude of the positive peak P2 is Api and occurs at time Tpi. The amplitude of the negative peak Pl is Am and occurs at time Tm. The peak-to-peak amplitude is Apt + Am. A recorded ECAP will typically have a maximum peak-to-peak amplitude in the range of microvolts and a duration of 2 to 3 ms.

[0036] The stimulator 100 is further configured to measure the intensity of ECAPs 170 propagating along nerve 180, whether such ECAPs are evoked by the stimulus from electrodes 2 and 4, or otherwise evoked. To this end, any electrodes of the array 150 may be selected by the electrode selection module 126 to serve as recording electrode 6 and reference electrode 8, whereby the electrode selection module 126 selectively connects the chosen electrodes to the inputs of the measurement circuitry 128. Thus, signals sensed by the measurement electrodes 6 and 8 subsequent to the respective stimuli are passed to the measurement circuitry 128, which may comprise a differential amplifier and an analog-to-digital converter (ADC), as illustrated in Fig. 3. The recording electrode and the reference electrode are referred to as the measurement electrode configuration. The measurement circuitry 128 for example may operate in accordance with the teachings of the above- mentioned International Patent Publication No. WO2012/155183.

[0037] Signals sensed by the measurement electrodes 6, 8 and processed by measurement circuitry 128 are further processed by an ECAP detector implemented within controller 116, configured by control programs 122, to obtain information regarding the effect of the applied stimulus upon the nerve 180. In some implementations, the sensed signals are processed by the ECAP detector in a manner which measures and stores one or more characteristics from each evoked neural response or group of evoked neural responses contained in the sensed signal. In one such implementation, the characteristics comprise a peak-to-peak ECAP amplitude in microvolts (pV). For example, the sensed signals may be processed by the ECAP detector to determine the peak-to-peak ECAP amplitude in accordance with the teachings of International Patent Publication No. W02015/074121, the contents of which are incorporated herein by reference. Alternative implementations of the ECAP detector may measure and store an alternative characteristic from the neural response, or may measure and store two or more characteristics from the neural response.

[0038] Stimulator 100 applies stimuli over a potentially long period such as days, weeks, or months and during this time may store characteristics of neural responses, clinical settings, paraesthesia target level, and other operational parameters in memory 118. To effect suitable SCS therapy, stimulator 100 may deliver tens, hundreds or even thousands of stimuli per second, for many hours each day. Each neural response or group of responses generates one or more characteristics such as a measure of the intensity of the neural response. Stimulator 100 thus may produce such data at a rate of tens or hundreds of Hz, or even kHz, and over the course of hours or days this process results in large amounts of clinical data 120 which may be stored in the memory 118. Memory 118 is however necessarily of limited capacity and care is thus required to select compact data forms for storage into the memory 118, to ensure that the memory 118 is not exhausted before such time that the data is expected to be retrieved wirelessly by external device 192, which may occur only once or twice a day, or less.

[0039] An activation plot, or growth curve, is an approximation to the relationship between stimulus intensity (e.g. an amplitude of the current pulse 160) and intensity of neural response 170 evoked by the stimulus (e.g. an ECAP amplitude). Fig. 4 illustrates an idealised activation plot 402 for one posture of the patient 108. The activation plot 402 shows a linearly increasing ECAP amplitude for stimulus intensity values above a threshold 404 referred to as the ECAP threshold. The ECAP threshold exists because of the binary nature of fibre recruitment; if the field strength is too low, no fibres will be recruited. However, once the field strength exceeds a threshold, fibres begin to be recruited, and their individual evoked action potentials are independent of the strength of the field. The ECAP threshold 404 therefore reflects the field strength at which significant numbers of fibres begin to be recruited, and the increase in response intensity with stimulus intensity above the ECAP threshold reflects increasing numbers of fibres being recruited. Below the ECAP threshold 404, the ECAP amplitude may be taken to be zero. Above the ECAP threshold 404, the activation plot 402 has a positive, approximately constant slope indicating a linear relationship between stimulus intensity and the ECAP amplitude. Such a relationship may be modelled as:

(S s - T), s > T y⁼ t 0, s < T (1)

[0040] where 5 is the stimulus intensity, y is the ECAP amplitude, T is the ECAP threshold and S is the slope of the activation plot (referred to herein as the patient sensitivity). The sensitivity 5 and the ECAP threshold T are the key parameters of the activation plot 402.

[0041] Fig. 4 also illustrates a discomfort threshold 408, which is a stimulus intensity above which the patient 108 experiences uncomfortable or painful stimulation. Fig. 4 also illustrates a perception threshold 410. The perception threshold 410 corresponds to an ECAP amplitude that is barely perceptible by the patient. There are a number of factors which can influence the position of the perception threshold 410, including the posture of the patient. Perception threshold 410 may correspond to a stimulus intensity that is greater than the ECAP threshold 404, as illustrated in Fig.

4, if patient 108 does not perceive low levels of neural activation. Conversely, the perception threshold 410 may correspond to a stimulus intensity that is less than the ECAP threshold 404, if the patient has a high perception sensitivity to lower levels of neural activation than can be detected in an ECAP, or if the signal to noise ratio of the ECAP is low.

[0042] For effective and comfortable operation of an implantable neuromodulation device such as the stimulator 100, it is desirable to maintain stimulus intensity within a therapeutic range. A stimulus intensity within a therapeutic range 412 is above the ECAP threshold 404 and below the discomfort threshold 408. In principle, it would be straightforward to measure these limits and ensure that stimulus intensity, which may be closely controlled, always falls within the therapeutic range 412. However, the activation plot, and therefore the therapeutic range 412, varies with the posture of the patient 108.

[0043] To keep the applied stimulus intensity within the therapeutic range as patient posture varies, in some implementations an implantable neuromodulation device such as the stimulator 100 may adjust the applied stimulus intensity based on a feedback variable that is determined from one or more measured ECAP characteristics. In one implementation, the device may adjust the stimulus intensity to maintain the measured ECAP amplitude at a target response intensity. For example, the device may calculate an error between a target ECAP amplitude and a measured ECAP amplitude, and adjust the applied stimulus intensity to reduce the error as much as possible, such as by adding the scaled error to the current stimulus intensity. A neuromodulation device that operates by adjusting the applied stimulus intensity based on a measured ECAP characteristic is said to be operating in closed- loop mode and will also be referred to as a closed-loop neural stimulation (CLNS) device. By adjusting the applied stimulus intensity to maintain the measured ECAP amplitude at an appropriate target response intensity, such as a target ECAP amplitude, a CLNS device will generally keep the stimulus intensity within the therapeutic range as patient posture varies.

[0044] A CLNS device comprises a stimulator that takes a stimulus intensity value and converts it into a neural stimulus comprising a sequence of electrical pulses according to a predefined stimulation pattern. The stimulation pattern is parametrised by multiple stimulus parameters including stimulus amplitude, pulse width, number of phases, order of phases, number of stimulus electrode poles (two for bipolar, three for tripolar etc.), and stimulus rate or frequency. At least one of the stimulus parameters, for example the stimulus amplitude, is controlled by the feedback loop.

[0045] In an example CLNS system, a user (e.g. the patient or a clinician) sets a target response intensity, and the CLNS device performs proportional-integral-differential (PID) control. In some implementations, the differential contribution is disregarded and the CLNS device uses a first order integrating feedback loop. The stimulator produces stimulus in accordance with a stimulus intensity parameter, which evokes a neural response in the patient. The intensity of an evoked neural response (e g. an ECAP) is measured by the CLNS device and compared to the target response intensity.

[0046] The measured neural response intensity, and its deviation from the target response intensity, is used by the feedback loop to determine possible adjustments to the stimulus intensity parameter to maintain the neural response at the target intensity. If the target intensity is properly chosen, the patient receives consistently comfortable and therapeutic stimulation through posture changes and other perturbations to the stimulus / response behaviour.

[0047] Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system 300, according to one implementation of the present technology. The system 300 comprises a stimulator 312 which converts a stimulus intensity parameter (for example a stimulus current amplitude) s, in concert with a set of predefined stimulus parameters, to a neural stimulus comprising a sequence of electrical pulses on the stimulus electrodes (not shown in Fig. 5). According to one implementation, the predefined stimulus parameters comprise the number and order of phases, the number of stimulus electrode poles, the pulse width, and the stimulus rate or frequency.

[0048] The generated stimulus crosses from the electrodes to the spinal cord, which is represented in Fig. 5 by the dashed box 308. The box 309 represents the evocation of a neural response y by the stimulus as described above. The box 311 represents the evocation of an artefact signal a, which is dependent on stimulus intensity and other stimulus parameters, as well as the electrical environment of the measurement electrodes. Various sources of measurement noise n, as well as the artefact a, may add to the evoked response y at the summing element 313 to form the sensed signal r, including: electrical noise from external sources such as 50 Hz mains power; electrical disturbances produced by the body such as neural responses evoked not by the device but by other causes such as peripheral sensory input; EEG; EMG; and electrical noise from measurement circuitry 318. [0049] The neural recruitment arising from the stimulus is affected by mechanical changes, including posture changes, walking, breathing, heartbeat and so on. Mechanical changes may cause impedance changes, or changes in the location and orientation of the nerve fibres relative to the electrode array(s). As described above, the intensity of the evoked response provides a measure of the recruitment of the fibres being stimulated. In general, the more intense the stimulus, the more recruitment and the more intense the evoked response. An evoked response typically has a maximum amplitude in the range of microvolts, whereas the voltage resulting from the stimulus applied to evoke the response is typically several volts.

[0050] Measurement circuitry 318, which may be identified with measurement circuitry 128, amplifies the sensed signal r (including evoked neural response, artefact, and measurement noise), and samples the amplified sensed signal r to capture a “signal window” 319 comprising a predetermined number of samples of the amplified sensed signal r. The ECAP detector 320 processes the signal window 319 and outputs a measured neural response intensity d. In one implementation, the neural response intensity comprises a peak-to-peak ECAP amplitude. The measured response intensity d (an example of a feedback variable) is input into the feedback controller 310. The feedback controller 310 comprises a comparator 324 that compares the measured response intensity d to a target ECAP amplitude as set by the target ECAP controller 304 and provides an indication of the difference between the measured response intensity d and the target ECAP amplitude. This difference is the error value, e.

[0051] The feedback controller 310 calculates an adjusted stimulus intensity parameter, s, with the aim of maintaining a measured response intensity d equal to the target ECAP amplitude. Accordingly, the feedback controller 310 adjusts the stimulus intensity parameter 5 to minimise the error value, e. In one implementation, the controller 310 utilises a first order integrating function, using a gain element 336 and an integrator 338, in order to provide suitable adjustment to the stimulus intensity parameter 5. According to such an implementation, the current stimulus intensity parameter may be determined by the feedback controller 310 as s = f Kedt (2)

[0052] where K is the gain of the gain element 336 (the controller gain). This relation may also be represented as

8s = Ke [0053] where §5 is an adjustment to the current stimulus intensity parameter s.

[0054] A target ECAP amplitude is input to the feedback controller 310 via the target ECAP controller 304. In one implementation, the target ECAP controller 304 provides an indication of a specific target ECAP amplitude. In another implementation, the target ECAP controller 304 provides an indication to increase or to decrease the present target ECAP amplitude. The target ECAP controller 304 may comprise an input into the CLNS system 300, via which the patient or clinician can input a target ECAP amplitude, or indication thereof. The target ECAP controller 304 may comprise memory in which the target ECAP amplitude is stored, and from which the target ECAP amplitude is provided to the feedback controller 310.

[0055] A clinical settings controller 302 provides clinical settings to the system 300, including the feedback controller 310 and the stimulus parameters for the stimulator 312 that are not under the control of the feedback controller 310. In one example, the clinical settings controller 302 may be configured to adjust the controller gain K of the feedback controller 310 to adapt the feedback loop to patient sensitivity. The clinical settings controller 302 may comprise an input into the CLNS system 300, via which the patient or clinician can adjust the clinical settings. The clinical settings controller 302 may comprise memory in which the clinical settings are stored, and are provided to components of the system 300.

[0056] In some implementations, two clocks (not shown) are used, being a stimulus clock operating at the stimulus frequency (e.g. 60 Hz) and a sample clock for sampling the sensed signal r (for example, operating at a sampling frequency of 16 kHz). As the ECAP detector 320 is linear, only the stimulus clock affects the dynamics of the CLNS system 300. On the next stimulus clock cycle, the stimulator 312 outputs a stimulus in accordance with the adjusted stimulus intensity s. Accordingly, there is a delay of one stimulus clock cycle before the stimulus intensity is updated in light of the error value e.

[0057] Fig. 7 is a block diagram of a neural stimulation system 700. The neural stimulation system 700 is centred on a neuromodulation device 710. In one example, the neuromodulation device 710 may be implemented as the stimulator 100 of Fig. 1, either implanted within a patient (not shown) or external to the patient (as shown). The neuromodulation device 710 is connected, e g. wirelessly, to a remote controller (RC) 720. The remote controller 720 is a portable computing device that provides the patient with control of their stimulation in the home environment by allowing control of the functionality of the neuromodulation device 710, including one or more of the following functions: enabling or disabling stimulation; adjustment of stimulus intensity or target response intensity; and selection of a stimulation control program from the control programs stored on the neuromodulation device 710.

[0058] The charger 750 is configured to recharge a rechargeable power source of the neuromodulation device 710. The recharging is illustrated as wireless in Fig. 7 but may be wired in alternative implementations.

[0059] The neuromodulation device 710 is wirelessly connected to a Clinical System Transceiver (CST) 730. The wireless connection may be implemented as the transcutaneous communications channel 190 of Fig. 1. The CST 730 acts as an intermediary between the neuromodulation device 710 and the Clinical Interface (CI) 740, to which the CST 730 is connected. A wired connection is shown in Fig. 7, but in other implementations, the connection between the CST 730 and the CI 740 is wireless.

[0060] The CI 740 may be implemented as the external computing device 192 of Fig. 1. The CI 740 is configured to program the neuromodulation device 710 and recover data stored on the neuromodulation device 710. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the CI 740.

Diagnosing neuropathic pain

[0061] Fig. 8A is a simplified illustration of the human spinal cord 800, in cross-section at a typical vertebra. (In one simplification, the bony structures are not illustrated in Fig. 8A.) A spinal nerve 830, comprising somatic motor neurons (efferents) 840 and somatic sensory neurons (afferents) 820 from the periphery, bifurcates into two branches which enter the spinal cord separately: the ventral root 860, comprising motor neurons 840, and the dorsal root 850, containing sensory neurons 820. The sensory neurons 820 of the dorsal root 850 pass through a thickened region referred to as the dorsal root ganglion (DRG) 810 before entering the spinal cord at the dorsal horn 870. The ventral root 860 enters the ventral horn 880. Sensory afferents 820 eventually enter the dorsal column (DC) 890 where they are activatable via an electrode array inserted into the dorsal epidural space as described above. [0062] It has been hypothesised that in a healthy state the DRG 810 normally acts as an attenuator on sensory action potentials propagating from the periphery to the spinal cord along sensory afferents 820. However, it may be that in patients with neuropathic pain, this attenuation effect is diminished, abolished or reversed such that the signals are either insufficiently attenuated, unaltered or amplified as they pass through the DRG. According to this hypothesis, the attenuation/amplification effect of the DRG may therefore, if measured, be used as a diagnostic indicator of neuropathic pain arising from abnormal DRG function.

[0063] As illustrated in Fig. 8B, to measure the amplifying effect of the DRG 810 of the appropriate vertebra for the affected dermatome on action potentials, in one implementation, one or more lateral sensing contacts (e.g. measurement electrode 893) are positioned laterally to (at the peripheral or distal side of) the DRG 810, and one or more medial sensing contacts (e g. measurement electrode 892) are positioned medially to (at the central or proximal side of) the DRG 810. A percutaneous (linear) electrode array 891 is fed through an epidural needle so that the array passes through the neural foramen at the appropriate vertebra for the affected dermatome and extends laterally alongside the DRG 810 and spinal nerve 830. Electrodes 892-894 of the array 891 may thereby be located both laterally and medially relative to the DRG 810 to act as sensing contacts. Electrodes 894 of the array 891, located more laterally to the DRG relative to the lateral sensing electrode 893, may act as stimulus and return electrodes for the delivery of stimuli to the sensory afferents 820 as described above.

[0064] In another implementation, a percutaneous electrode array may be inserted in the opposite direction to array 891, via a trans-foraminal needle passed through the neural foramen at the appropriate vertebra for the affected dermatome. Electrodes of the array may thereby be located both laterally and medially to the DRG to act as sensing contacts. Electrodes of the array located laterally to the DRG may also act as stimulus and return electrodes for the delivery of stimuli as described above.

[0065] In another implementation, needles with contacts on their tips may be temporarily inserted both medially and laterally to the DRG. In such an implementation, the sensing of action potentials at each location may be referenced to the system ground 130, thereby resulting in single-ended action potentials as described above.

[0066] Fig. 9 is a flow chart illustrating a method 900 of diagnosing neuropathic pain according to one implementation of the present technology. The method 900 may be carried out by the controller 116 of the neuromodulation device 710. Alternatively, the method 900 may be carried out by a processor of an external device 192, such as the clinical interface 740, in communication with the neuromodulation device 710. In such an implementation, the controller 116 of the neuromodulation device 710 may be configured to forward the captured signal windows to the external device 192 for analysis by the processor of the external device according to the steps of the method 900. In implementations in which the neuromodulation device 710 is not implanted but is external to the patient, the external neuromodulation device 710 and the external device 192 may be integrated within a single device referred to as a neuropathic pain detection device (NPDD).

[0067] The method 900 starts at step 910, in which stimuli are delivered at the affected dermatome or at the corresponding spinal nerve 830. The stimuli at the affected dermatome may be delivered either electrically, e.g. transcutaneously using a transcutaneous electrical nerve stimulation (TENS) pad or needle, or mechanically, e g. using friction. Alternatively, step 910 may use one or more of the contacts 894 inserted laterally to the DRG as described above as a stimulus electrode configuration through which to deliver the stimuli at the spinal nerve 830.

[0068] In implementations in which the method 900 is carried out by the processor of an external device 192, the processor may be configured to instruct the controller 116 of the neuromodulation device 710 to deliver the stimuli at step 910.

[0069] Step 920 then measures characteristics of the action potentials in the signal windows captured subsequent to the respective delivered stimuli by the sensing contact(s) 893 located laterally to the DRG. The action potentials may be either ECAPs evoked by the stimuli delivered at step 910, or endogenous non-evoked action potentials. In one implementation, step 920 implements an ECAP detector as described above to measure amplitudes of the ECAPs or non-evoked action potentials.

[0070] Step 930 then measures characteristics of the action potentials in the signal windows captured subsequent to the respective delivered stimuli by the sensing contact(s) 892 located medially to the DRG. The action potentials may be either ECAPs evoked by the stimuli delivered at step 910, or endogenous non-evoked action potentials. In one implementation, step 930 uses an ECAP detector as described above to measure amplitudes of the ECAPs or non-evoked action potentials.

[0071] Step 940 then measures the attenuation/amplification effect of the DRG on the action potentials lateral to the DRG. In one implementation, step 940 constructs two histograms over a predetermined period, e.g. several seconds: a first histogram of characteristics (such as amplitude) of a plurality of action potentials as measured lateral to the DRG, and a second histogram of characteristics of the plurality of action potentials as measured medial to the DRG. The DRG effect may then be computed as the ratio between a representative value (e.g. the median or mode) of the second (medial) histogram and the same representative value of the first (lateral) histogram. In another implementation, the DRG effect may be quantified as the ratio of the number (or count) of measurable medial action potentials to the number (or count) of measurable lateral action potentials. A measurable action potential is an action potential whose measured amplitude exceeds a threshold that discriminates action potentials from measurement noise.

[0072] Step 950 tests whether amplification of action potentials has occurred in the DRG. In one implementation, if the measured DRG effect from step 940 exceeds a threshold, for example (in the implementation in which the DRG effect is the ratio of representative values) a threshold of 1 (0 dB), amplification has probably occurred. If not (“N”), step 960 communicates an indicator that the pain associated with the affected dermatome is probably not neuropathically arising from the DRG. If so (“Y”), step 970 communicates an indicator that the pain associated with the affected dermatome is probably neuropathically arising from the DRG.

[0073] While the process of Fig. 9 provides a binary (Y/N) measure of severity of neuropathic pain, it is to be noted that the DRG effect measure generated by step 940 of the method 900 may be used in a number of ways (in addition to its above-described use in neuropathic pain diagnosis) as an objective non-binary measure of severity of neuropathic pain. In one implementation, the DRG effect measure may itself be used as an objective non-binary measure of severity of neuropathic pain, possibly after mapping to a normalised scale such [0, 1], In another implementation, the DRG effect measure may be used to develop an objective measure of efficacy of a pain therapy, e.g, closed-loop neural stimulation therapy as described above, for the neuropathic pain. In one implementation, the efficacy of a therapy may be objectively measured as the change in the DRG effect measure before and after applying the therapy. Such an objective measure of efficacy may be used in one or more of the following settings:

• during implantation, to confirm proper placement of the electrode array used for the therapeutic stimulation;

• during programming, to determine a therapeutically effective value for neural stimulation therapy parameters such as the target ECAP amplitude;

• during therapy, to monitor the efficacy of the therapy. [0074] In the latter setting, which is suitable for the implementation in which the method 900 is implemented by the neuromodulation device 710, steps 910 to 940 of the method 900 may be carried out repeatedly to derive a sequence of objective measures of efficacy. Each efficacy measure in the sequence may be determined as a difference between an initial, baseline DRG effect measure and a current value of the DRG effect measure. If the measure of efficacy starts to decrease over time, or decreases beyond a predetermined threshold, an alert may be raised by the neuromodulation device 710 to the patient, e.g. via the remote controller 720, that clinical settings need to be adjusted or other remedial action taken, such a re-programming of the neuromodulation device 710.

[0075] It will be appreciated by persons skilled in the art that numerous variations or modifications may be made to the invention as shown in the specific implementations without departing from the spirit or scope of the invention as broadly described. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present invention. The disclosed implementations are, therefore, to be considered in all respects as illustrative and not limiting or restrictive.

INDUSTRIAL APPLICABILITY

[0076] It is apparent from the above that the arrangements described are applicable to the health care industries.

LABEL LIST

Claims

CLAIMS:

1. A method of measuring neuropathic pain associated with an affected dermatome of a patient, the method comprising: measuring at least one lateral characteristic value of at least one action potential lateral to a dorsal root ganglion (DRG) of sensory afferents from the affected dermatome; measuring at least one medial characteristic value of at least one action potential medial to the DRG of sensory afferents from the affected dermatome; measuring an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generating a measure of neuropathic pain from the DRG effect measure.

2. The method of claim 1, wherein the at least one action potential is an evoked compound action potential (ECAP).

3. The method of claim 2, further comprising delivering stimuli laterally to the DRG so as to evoke the ECAP(s).

4. The method of claim 3, wherein the delivering comprises delivering electrical stimuli to the sensory afferents proximal to the DRG.

5. The method of claim 3, wherein the delivering comprises delivering peripheral stimuli at the affected dermatome.

6. The method of claim 5, wherein the delivering comprises delivering electrical stimuli transcutaneously.

7. The method of any one of claims 1 to 6, wherein each measured characteristic value is action potential amplitude.

8. The method of claim 7, wherein measuring the effect of the DRG comprises: constructing a medial histogram of a plurality of measured medial amplitudes; constructing a lateral histogram of a plurality of measured lateral amplitudes; and computing the effect of the DRG as a ratio between a representative value of the medial histogram and a representative value of the lateral histogram.

9. The method of any one of claims 1 to 6, wherein the measured medial characteristic value and the measured lateral characteristic value comprise a number of measurable medial and lateral action potentials respectively.

10. The method of claim 9, wherein measuring the effect of the DRG comprises computing the effect of the DRG as a ratio between the number of measurable medial action potentials and the number of measurable lateral action potentials.

11. The method of any one of claims 1 to 10, wherein generating a measure of neuropathic pain comprises determining whether the measured DRG effect exceeds a threshold.

12. The method of claim 11, further comprising communicating, based on the determining, an indicator that pain associated with the affected dermatome is neuropathic.

13. The method of any one of claims 1 to 10, wherein the measure of neuropathic pain is a nonbinary measure of severity of neuropathic pain.

14. The method of claim 13, wherein the measure of severity is a pre-therapy measure of severity, the method further comprising: applying a therapy for the neuropathic pain; repeating the measuring of a severity of neuropathic pain to obtain a post-therapy measure of severity of neuropathic pain; and computing a measure of efficacy of the therapy from the pre-therapy measure of severity of neuropathic pain and the post-therapy measure of severity of neuropathic pain.

15. A device for measuring neuropathic pain associated with an affected dermatome of a patient, the device comprising: measurement circuitry configured to: capture at least one lateral signal window from at least one signal sensed laterally to a dorsal root ganglion (DRG) of sensory afferents from the affected dermatome, the at least one signal sensed via one or more measurement electrodes located laterally to the DRG, and capture at least one medial signal window from at least one signal sensed medially to the DRG via one or more measurement electrodes located medially to the DRG; and a control unit configured to: measure, in the at least one lateral signal window, at least one lateral characteristic value of at least one action potential lateral to the DRG; measure, in the at least one medial signal window, at least one medial characteristic value of at least one action potential medial to the DRG; measure an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generate a measure of neuropathic pain from the DRG effect measure.

16. The device of claim 15, wherein the at least one action potential is an evoked compound action potential (ECAP).

17. The device of claim 16, wherein the control unit is further configured to instruct a stimulus source to deliver stimuli laterally to the DRG so as to evoke the ECAPs.

18. The device of claim 17, wherein the control unit is further configured to instruct the stimulus source to deliver stimuli to the sensory afferents proximal to the DRG.

19. The device of claim 17, wherein the stimuli are delivered peripherally at the affected dermatome.

20. The device of claim 19, wherein the stimuli are electrical stimuli delivered transcutaneously.

21. The device of any one of claims 15 to 20, wherein the at least one measured characteristic value is action potential amplitude.

22. The device of claim 21, wherein measuring the effect of the DRG comprises: constructing a medial histogram of a plurality of measured medial amplitudes; constructing a lateral histogram of a plurality of measured lateral amplitudes; and computing the effect of the DRG as a ratio between a representative value of the medial histogram and a representative value of the lateral histogram.

23. The device of any one of claims 15 to 20, wherein the measured medial characteristic value and the measured lateral characteristic value comprise a number of measurable medial and lateral action potentials respectively.

24. The device of claim 23, wherein measuring the effect of the DRG comprises computing the effect of the DRG as a ratio between the number of measurable medial action potentials and the number of measurable lateral action potentials.

25. The device of any one of claims 15 to 24, wherein the control unit is further configured to determine whether the measured DRG effect exceeds a threshold.

26. The device of claim 25, wherein the control unit is further configured to communicate, based on the determining, an indicator that pain associated with the affected dermatome is neuropathic.

27. The device of any one of claims 15 to 24, wherein the measure of neuropathic pain is a nonbinary measure of severity of neuropathic pain.

28. The device of claim 27, wherein the measure of severity is a pre-therapy measure of severity, and the control unit is further configured to: apply a therapy for the neuropathic pain; repeat the measuring of a severity of neuropathic pain to obtain a post-therapy measure of severity of neuropathic pain; and compute a measure of efficacy of the therapy from the pre-therapy measure of severity of neuropathic pain and the post-therapy measure of severity of neuropathic pain.

29. A system comprising: measurement circuitry configured to: capture at least one lateral signal window from at least one signal sensed laterally to a dorsal root ganglion (DRG) of sensory afferents from an affected dermatome, the at least one signal sensed via one or more measurement electrodes located laterally to the DRG, and capture at least one medial signal window from at least one signal sensed medially to the DRG via one or more measurement electrodes located medially to the DRG; and a processor configured to: measure, in the at least one lateral signal window, at least one lateral characteristic value of at least one action potential lateral to the DRG; measure, in the at least one medial signal window, at least one medial characteristic value of at least one action potential medial to the DRG; measure an effect of the DRG on the at least one action potential lateral to the DRG using the at least one lateral characteristic value and the at least one medial characteristic value; and generate a measure of neuropathic pain from the DRG effect measure.

30. The system of claim 29, further comprising: a plurality of electrodes including the one or more measurement electrodes located laterally to the DRG, and the one or more measurement electrodes located medially to the DRG.

31 . The system of any one of claims 29 to 30, further comprising an external device in communication with the measurement circuitry.

32. The system of claim 31, wherein the processor is part of the external device.

33. The system of any one of claims 29 to 32, wherein the measurement circuitry and the processor form part of an integrated diagnostic device.