Background of the Invention

[0001] The present invention relates to a system for stimulating neurons and in one particular example, to a system for stimulating neurons within at least one of the dorsal column and dorsal hom, such as dendrites in a spinal cord, dorsal hom, or dorsal column.

Description of the Prior Art

[0002] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[0003] Spinal cord stimulation is a known technique for relieving chronic pain. Typically, the stimulation is targeted at axons in the dorsal columns of the spinal cord, which is also known as paresthesia spinal cord stimulation. This type of stimulation is designed to stimulate axons in the spinal cord, which works well for pain relief, however, the stimulation are of limited efficacy. In some cases, the loss of efficacy may be about 25%.

[0004] US-9,089,708 provides systems and methods for stimulation of neurological tissue apply a stimulation waveform that is derived by a developed genetic algorithm, which may be coupled to a computational model of extracellular stimulation of a mammalian myelinated axon. The waveform is optimized for energy efficiency.

Summary of the Present Invention

[0005] In one broad form an aspect of the present invention seeks to provide a system for stimulating neurons, the system includes a lead including a lead body; at least one electrode carried by a distal portion of the lead body, the at least one electrode being configured to be provided proximate a dorsal hom in the spinal cord of a subject; and at least one pair of connections extending from the electrodes; and a signal generator electrically coupled to the at least one connection and configured to generate electrical signals that are applied to the at least one electrode, and wherein the electrical signals include waveforms to stimulate neurons within at least one of the spinal cord, dorsal column and dorsal hom.

[0006] In one embodiment, the waveforms include at least one of square waveforms; non square waveforms; an exponentially waveform; a ramp waveform; a sine waveform; and a triangular waveform.

[0007] In one embodiment, the exponential waveform is defined by a function of fix) = b ^kx .

[0008] In one embodiment, the ramp waveform is defined by a gradient that is of a positive value or negative value.

[0009] In one embodiment, the lead body includes: at least two spaced apart electrodes carried by the distal portion of the lead body; and at least two connections.

[0010] In one embodiment, the lead body includes at least two spaced apart double electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.

[0011] In one embodiment, the lead body includes at least two spaced apart outer electrodes carried by the distal portion of the lead body; at least two spaced apart inner electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.

[0012] In one embodiment, the lead body includes an electrode array including two spaced apart outer electrodes; and a plurality of spaced apart inner electrodes.

[0013] In one embodiment, the at least one electrode has a length that is at least one of less than 8.5mm; less than 9mm; less than 9.5mm; less than 10mm; less than 10.5mm; less than 11mm; less than 11.5mm; less than 12mm; greaterthan 1mm; greaterthan 1.5mm; greater than 2mm; greater than 2.5mm; greater than 3mm; about 3-8mm; about 3mm; about 4mm; about 5mm; about 6mm; about 7mm; and about 8mm.

[0014] In one embodiment, multiple electrodes are spaced by at least one of less than 12mm; less than 10mm; less than 8mm; less than 6mm; less than 4mm; greaterthan 1mm; greaterthan 1 5mm; greaterthan 2.0mm; greaterthan 2.5mm; about 3-4mm; about 3mm; about 4mm; about 3.3mm; about 3.4mm; and about 3.5mm. [0015] In one embodiment, the lead body includes a section between electrodes that is at least one of electrically non-conductive and flexible.

[0016] In one embodiment, the pulse has a width of at least one of greater than SOOps: greater than 900ps; and about lOOOps.

[0017] In one embodiment, the electrical signals are signals having a frequency that is at least one of greater than 50Hz; greater than 75Hz; greater than 100Hz; and about 100Hz.

[0018] In one embodiment, the electrical signals are frequency modulated.

[0019] In one embodiment, the electrical signals are frequency modulated about a target frequency.

[0020] In one embodiment, the electrical signals are modulated at least one of: by less than ±30% of the target frequency; by less than ±25% of the target frequency; by more than ±15% of the target frequency; by more than ±10% of the target frequency; by about ±20% of the target frequency; stochastically; and, in accordance with a distribution about the target frequency.

[0021] In one embodiment, the electrical signals include: a first electrical signal having a first frequency; and, a second electrical signal having a second frequency different to the first frequency, and wherein the first and second signals are superposed to generate electrical signals having: an average frequency corresponding to a target frequency; and, a beat frequency.

[0022] In one embodiment, the beat frequency is between 4Hz and 8Hz.

[0023] In one embodiment, the target frequency is at least one of: greater than 50Hz; greater than 75Hz; greater than 100Hz; and, about 100Hz.

[0024] In one embodiment, the electrical signals are signals having a duty cycle that is at least one of about 5%; about 10%; about 15%; about 20%; and about 50%.

[0025] In one embodiment, the electrical signals are signals having a voltage that is at least one of less than 50V; less than 25V; less than 10V; less than 5 V; less than 2V; less than IV; greater than 0.1V; greater than 0.2V; greater than 0.5V; and greater than IV. [0026] In one embodiment, the electrical signals are signals having a current that is at least one of less than 50A; less than 25A; less than 10A; less than 5A; less than 2A; less than 1A; greater than 0.1 A; greater than 0.2A; greater than 0.5A; and greater than 1A.

[0027] In one embodiment, the waveforms have a magnitude that is at least one of 10-60% of a paresthesia threshold; 40-80% of a paresthesia threshold; 60-99% of a paresthesia threshold; about 40% of a paresthesia threshold; about 60% of a paresthesia threshold; and about 80% of a paresthesia threshold.

[0028] In one embodiment, the one or more electrodes includes at least a pair of first and second electrodes placed at least one of approximate a thoracic spine of the subject; across T8 and T9 of a thoracic spine of the subject; and across T9 and T10 of a thoracic spine of the subject.

[0029] In one embodiment, the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively, wherein the first and second signals include a plurality of pulses and wherein pulses in the first signal have opposing polarities to pulses in the second signal.

[0030] In one embodiment, in the sequence the first electrical signal includes a cathodic signal and the second signal includes an anodic signal.

[0031] In one embodiment the system is configured to stimulate theta waves.

[0032] In one embodiment the method is configured to stimulate dendrites in the dorsal hom or dorsal column.

[0033] In one broad form an aspect of the present invention seeks to provide a method for stimulating neurons, the system includes providing a lead including a lead body; at least one electrode carried by a distal portion of the lead body, the at least one electrode being configured to be provided proximate a dorsal hom in the spinal cord of a subject; and at least one pair of connections extending from the electrodes; and, using a signal generator electrically coupled to the at least one connection and configured to generate electrical signals that are applied to the at least one electrode, and wherein the electrical signals include waveforms to stimulate neurons within at least one of the spinal cord, dorsal column and dorsal hom.

[0034] In one embodiment, the waveforms include at least one of square waveforms; non square waveforms; an exponentially waveform; a ramp waveform; a sine waveform and a triangular waveform.

[0035] In one embodiment, the exponential waveform is defined by a function of fix) = b ^kx .

[0036] In one embodiment, the ramp waveform is defined by a gradient that is of a positive value or negative value.

[0037] In one embodiment, the lead body includes at least two spaced apart electrodes carried by the distal portion of the lead body; and at least two connections.

[0038] In one embodiment, the lead body includes at least two spaced apart double electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.

[0039] In one embodiment, the lead body includes at least two spaced apart outer electrodes carried by the distal portion of the lead body; at least two spaced apart inner electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.

[0040] In one embodiment, the lead body includes an electrode array including two spaced apart outer electrodes; and a plurality of spaced apart inner electrodes.

[0041] In one embodiment, the at least one electrode has a length that is at least one of less than 8.5mm; less than 9mm; less than 9.5mm; less than 10mm; less than 10.5mm; less than 11mm; less than 11.5mm; less than 12mm; greaterthan 1mm; greaterthan 1.5mm; greater than 2mm; greater than 2.5mm; greater than 3mm; about 3-8mm; about 3mm; about 4mm; about 5mm; about 6mm; about 7mm; and about 8mm.

[0042] In one embodiment, multiple electrodes are spaced by at least one of less than 12mm; less than 10mm; less than 8mm; less than 6mm; less than 4mm; greaterthan 1mm; greaterthan 1 5mm; greaterthan 2.0mm; greaterthan 2.5mm; about 3-4mm; about 3mm; about 4mm; about 3.3mm; about 3.4mm; and about 3.5mm. [0043] In one embodiment, the lead body includes a section between electrodes that is at least one of electrically non-conductive and flexible.

[0044] In one embodiment, the pulse has a width of at least one of greater than SOOps: greater than 900ps; and about lOOOps.

[0045] In one embodiment, the electrical signals are signals having a frequency that is at least one of greater than 50Hz; greater than 75Hz; greater than 100Hz; and about 100Hz.

[0046] In one embodiment, the electrical signals are frequency modulated.

[0047] In one embodiment, the electrical signals are frequency modulated about a target frequency.

[0048] In one embodiment, the electrical signals are modulated at least one of: by less than ±30% of the target frequency; by less than ±25% of the target frequency; by more than ±15% of the target frequency; by more than ±10% of the target frequency; by about ±20% of the target frequency; stochastically; and, in accordance with a distribution about the target frequency.

[0049] In one embodiment, the electrical signals include: a first electrical signal having a first frequency; and, a second electrical signal having a second frequency different to the first frequency, and wherein the first and second signals are superposed to generate electrical signals having: an average frequency corresponding to a target frequency; and, a beat frequency.

[0050] In one embodiment, the beat frequency is between 4Hz and 8Hz.

[0051] In one embodiment, the target frequency is at least one of: greater than 50Hz; greater than 75Hz; greater than 100Hz; and, about 100Hz.

[0052] In one embodiment, the electrical signals are signals having a duty cycle that is at least one of about 5%; about 10%; about 15%; about 20%; and about 50%.

[0053] In one embodiment, the electrical signals are signals having a voltage that is at least one of less than 50V; less than 25V; less than 10V; less than 5 V; less than 2V; less than IV; greater than 0.1V; greater than 0.2V; greater than 0.5V; and greater than IV. [0054] In one embodiment, the electrical signals are signals having a current that is at least one of less than 50A; less than 25A; less than 10A; less than 5A; less than 2A; less than 1A; greater than 0.1 A; greater than 0.2A; greater than 0.5A; and greater than 1A.

[0055] In one embodiment, the waveforms have a magnitude that is at least one of 10-60% of a paresthesia threshold; 40-80% of a paresthesia threshold; 60-99% of a paresthesia threshold; about 40% of a paresthesia threshold; about 60% of a paresthesia threshold; and about 80% of a paresthesia threshold.

[0056] In one embodiment, the one or more electrodes includes at least a pair of first and second electrodes placed at least one of approximate a thoracic spine of the subject; across T8 and T9 of a thoracic spine of the subject; and across T9 and T10 of a thoracic spine of the subject.

[0057] In one embodiment, the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively, wherein the first and second signals include a plurality of pulses and wherein pulses in the first signal have opposing polarities to pulses in the second signal.

[0058] In one embodiment, in the sequence the first electrical signal includes a cathodic signal and the second signal includes an anodic signal.

[0059] In one embodiment the system is configured to stimulate neurons or dendrites in the dorsal hom or dorsal column.

[0060] In one embodiment the system is configured to stimulate theta waves.

[0061] It will be appreciated that the broad forms of the invention and their respective features can be used in conjunction and/or independently, and reference to separate broad forms is not intended to be limiting. Furthermore, it will be appreciated that features of the method can be performed using the system or apparatus and that features of the system or apparatus can be implemented using the method. Brief Description of the Drawings

[0062] Various examples and embodiments of the present invention will now be described with reference to the accompanying drawings, in which: -

[0063] Figure 1 is a schematic diagram of an example of a stimulation system for stimulating a dendrites in a spinal cord of a biological subject;

[0064] Figure 2 is a schematic diagram of an example of use of the system of Figure 1 with a biological subject;

[0065] Figure 3 is a schematic diagram of an example of a positioning of the lead of Figure 1 relative to a dorsal column in a biological subject;

[0066] Figures 4A and 4B are examples of non-square waveforms generated by a system for stimulating dendrites in a biological subject;

[0067] Figure 5 is an example of a pair of electrical signals generated by a system for stimulating dendrites in a biological subject;

[0068] Figure 6 is a schematic diagram of an example of an alternative lead electrode arrangement;

[0069] Figure 7 is a schematic diagram of an example of a lead electrode dimensions;

[0070] Figure 8 is a schematic diagram of an example of a lead internal structure;

[0071] Figure 9 is a schematic diagram of an example of use of an alternative nerve stimulation system for stimulating a dorsal column in a biological subject;

[0072] Figure 10 is a schematic diagram of an example of a controller for a nerve stimulation system;

[0073] Figure 11 A is a graph illustrating results of a study showing VAS (visual analogue scale) pain levels for different types of treatment; [0074] Figure 1 IB is a graph illustrating results of a study showing VAS pain levels for different treatment programs;

[0075] Figure 12A is a graph illustrating results of a study showing VAS pain levels for different treatment programs;

[0076] Figure 12B is a graph illustrating results of a study showing BPI (brief pain inventory) severity for different treatment programs;

[0077] Figure 12C is a graph illustrating results of a study showing mean BPI interference pain for different treatment programs;

[0078] Figure 12D is a graph illustrating results of a study showing EQ-5D (EuroQol- 5 Dimension) measures for different treatment programs;

[0079] Figure 12E is a graph illustrating results of a study showing EQ-5D VAS for different treatment programs;

[0080] Figure 13A is a graph illustrating results of a study showing clinician impression of change for different treatment programs;

[0081] Figure 13B is a graph illustrating results of a study showing patient satisfaction for different treatment programs; and,

[0082] Figure 13C is a graph illustrating results of a study showing responder analysis for different treatment programs.

Detailed Description of the Preferred Embodiments

[0083] An example of a system for stimulating neurons, such as dendrites will now be described in more detail with reference to Figures 1 to 3.

[0084] In this example, the system 100 includes a lead 110 including a lead body 111 having at least one pair electrodes 121, 122 carried by a distal portion 112 of the lead body 111. At least one pair of connections 123, 124 are provided extending from the pair of electrodes 121, 122. In this example, a pair of electrodes are shown, including a first electrode 121 and a second electrode 122, with a respective connections 123, 124 being provided for each electrode, although as will become apparent from the remaining description, this is not essential and different configurations of one or more electrodes could be used.

[0085] The electrodes 121, 122 are configured to be provided proximate the dorsal hom of a subject 201. In one example, this is achieved by inserting the lead via a posterior of a torso of the subject 201, so that the lead can be provided proximate a dorsal column in a thoracic region 202 of the spine 203. In this example, the lead is provided in the epidural space of the dorsal column, and it will be understood from this that the term proximate the dorsal hom, encompasses within the dorsal column or dorsal hom. However, this is not essential and alternatively, the leads can be placed midline or either side of midline. The electrodes 121, 122 may be placed approximate a cervical spine of the subject, across T8 and T9 or across T9 and T 10 of a thoracic spine of the subject for low back or leg pain.

[0086] As shown in Figure 3, the lead 111 can be positioned aligned with the spinal cord 304 so that electrodes 121, 122 are proximate (or within) dorsal column 308, allowing the dorsal column 308 to be modulated. In this example, the two leads 111 are positioned proximate to respective dorsal horns 309, allowing neurons, such as dendrites, within the dorsal horns and/or dorsal column to be stimulated. However, this is not essential, and the lead and electrodes could be positioned proximate any part of the spinal cord, including midline, or adjacent to midline, depending on the preferred implementation. In this instance, the waveform can still be configured to ensure stimulation of neurons within or adjacent to the dorsal hom or dorsal column.

[0087] A signal generator 130 is electrically connected to the connections 123, 124 and is configured to generate electrical signals that are applied to the electrodes 121, 122. In this regard, the electrical signals include waveforms to stimulate dendrites in the dorsal hom. Accordingly, the system provides an arrangement for stimulating neurons within or close to the dorsal hom and/or dorsal column in a biological subject, which effectively stimulates neurons such a dendrites by providing sufficient charge to perform the stimulation while minimising power required. The electrical signals may be able to swing over to the lateral aspect of the dorsal hom, and penetrate beyond Lamina I to active Lamina II-IV, so that dendrites or other neurons are stimulated with limited nerve root stimulation and limited paresthesia being produced.

[0088] A number of further features will now be described.

[0089] As previously mentioned, waveforms are generated to stimulate dendrites. The waveforms may be square waveforms, non-square wave waveforms, and more typically may include alternating or pulsed signals, and can be generated with a variety of different waveforms, including, but not limited to sine waves, triangular waves, sawtooth waves, exponential waves, including waves with an exponential ramp-up and/or ramp-down, Gaussian waveforms, or the like. Examples of the waveforms are shown in Figures 4A and 4B.

[0090] For example, as shown in Figure 4A, the non-square waveforms include at least one of an exponential waveform WF1-WF4; a ramp waveform WF5, WF6; a sine waveform WF7 and a triangular waveform WFx. The exponential waveforms WF1-WF4 can defined by a function of fix) = b ^kx .

[0091] The ramp waveforms WF5, WF ₆ can be defined by a gradient. The gradient of waveform WF5 is of a positive value, and the gradient of waveform WF ₆ is of a negative value. The waveforms may have an offset a from zero, as shown in Figure 4B.

[0092] The pulse may have a uniform width or variable widths, and the width may be of at least one of greater than 800ps, greater than 900ps, and about lOOOps. This allows the stimulation to spread current field out laterally (rib stimulation) and effectively stimulate dendrites. Dendrites are less responsive excitable to shorter pulses or less excitable for shorter pulses.

[0093] The electrical signals may have a frequency that is at least one of greater than 50Hz, greater than 75Hz, greater than 100Hz, and about 100Hz. In this regard, a target frequency of 100Hz is typically most effective at recruiting dendrites to relieve pain. However, some benefits might be achieved by additionally recruiting additional neuronal population pools, for example by using stimulation signals having different frequencies. For example, "Time- dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats" by Muhammad M Edhi, Lonne Heijmans, Kevin N Vanent, Kieman Bloye, Amanda Baanante, Ki-Soo Jeong, Jason Leung , Changfang Zhu, Rosana Esteller, Carl Y Saab, 2020 Nov 23;10(1):20358, demonstrates different frequencies can have different pain relieving effects in rats.

[0094] Accordingly, in one example, the electrical signals are frequency modulated, so that the frequency of the applied signals varies, to thereby allow additional pain relieving effects to be induced. The electrical signals are typically modulated about a target frequency, thereby maximising stimulation of dendrites, thereby ensuring maximum effectiveness of the therapy. In one example, the electrical signals are modulated by less than ±30% of the target frequency, less than ±25% of the target frequency, by more than ±15% of the target frequency, by more than ±10% of the target frequency and more preferably by about ±20% of the target frequency. Thus, for a target frequency of 100Hz, the signals are typically modulated between 82 and 118 Hz.

[0095] In one example, the modulation is performed stochastically, as random variations can further enhance the effectiveness of the modulation, as described for example in "Frequency- difference -dependent stochastic resonance in neural systems" by Daqing Guo, Matjaz Perc, Yangsong Zhang, Peng Xu, and Dezhong Yao in PHYSICAL REVIEW E 96, 022415 (2017). Nevertheless, to ensure adequate stimulation is performed at the target frequency, the signals are typically modulated in accordance with a distribution, such as a Gaussian distribution, aligned with the target frequency, so the majority of stimulation occurs at the target frequency, with less stimulation occurring further away from the target frequency. This maximises the effectiveness of dendrite stimulation, whilst also allowing benefits of stimulating other neuronal pools to be achieved.

[0096] In another example, the system can be configured to provide two different forms of complementary stimulation. In this example, the electrical signals include a first electrical signal having a first frequency and a second electrical signal having a second frequency different to the first frequency. Specifically, the first and second signals have slightly different frequencies, so that when the first and second signals are superposed they result in signals having an average frequency corresponding to a target frequency and a beat frequency. [0097] So, for example, instead of applying a 100Hz signal, two signals at 97Hz and 103Hz, respectively, can be applied simultaneously. The net effect is a signal with a mean frequency of 100Hz with an additional weak beat frequency generated by the neural structures of (103- 97Hz) 6Hz.

[0098] These signals conduct orthodromically and antidromically to the brain, and in particular to the thalamus, cortex and hippocampus, which are used by the brain in memory storage and retrieval and emotional processing. Typically the signals are selected so that the beat frequencies are of 10Hz or less, which corresponds to a "slow envelope modulation frequency", and which with moderate background noise in nerve firing (not too high or low) then stochastic resonance occurs, meaning the signals are transmitted strongly and are entrained by the system.

[0099] In one particular example, the beat frequency is between 4Hz and 8Hz, which corresponds to theta wave stimulation. The hippocampus uses theta activity for long term plasticity to assist in storing new memories, such as memories of pain. Typically pain interferes with theta rhythms in the brain, and a 100Hz signal in the hippocampus can reinforce existing stored memory of pain. See for example, "Impaired Spatial Memory Performance in a Rat Model of Neuropathic Pain Is Associated with Reduced Hippocampus-Prefrontal Cortex Connectivity” by Helder Cardoso-Cruz, Deolinda Lima, and Vasco Galhardo, The Journal of Neuroscience, February 6, 2013 · 33(6):2465-2480 · 2465.

[0100] Practically, this means that whilst 100Hz stimulation may recruit dendrites, and hence reduce pain, the memory of the original pain is retained, and hence when stimulation stops, pain will continue to be felt. However, by inducing theta stimulation in parallel with dendritic stimulation can allow pain memories to be overwritten with the reduced pain levels associated with the stimulation, meaning the reduction in pain continues after stimulation has ceased. This is particularly effective when the theta signal is strong, and also when an alpha/theta wave ratio is 2.

[0101] In one example, the applied signals have frequencies of 98/102 Hz, 97.5/102.5 Hz, 97/103 Hz, 96.5/103.5 Hz, 8Hz = 96/104 Hz, with the exact frequency combination being selected based on the subject’s response to the signals. In a further example, the frequencies can be varied by cycling between 98/102 Hz and 96/104 Hz, so that the beat frequency varies between 4Hz and 8Hz. In one example, this is performed stochastically, based on a distribution, such as a Gaussian distribution to produce theta band centred at a target beat frequency, such as 5.3Hz, depending on the subject response.

[0102] The electrical signals may further have a duty cycle that is at least one of about 5%, about 10%, about 15%, about 20% or about 50%. This allows dendrites to be stimulated to develop action potentials with efficient power consumption. In particular, by reducing the amount of stimulation performed, this reduces power consumption, so if the signals are only applied for 20% of the total therapy time, the battery life can be extended by up to five times. An additional benefit of this approach is that over time the body can develop a tolerance to the applied signals, so reducing the duty cycle so that signals are only applied periodically, can prevent he build-up of tolerance and hence ensure the treatment remains effective.

[0103] The electrical signals are signals can have a voltage that is less than 50V, less than 25V, less than 10V, less than 5V, less than 2V, less than IV, greater than 0.1V, greater than 0.2V, greater than 0.5V, and greater than IV.

[0104] The electrical signals are signals can have a current that is less than 50A, less than 25A, less than 10A, less than 5A, less than 2A, less than 1A, greater than 0.1A, greater than 0.2A, greater than 0.5A, and greater than 1A.

[0105] In one example, the electrical signals may have a magnitude that is at least one of 10- 60% of a paresthesia threshold, 40-80% of a paresthesia threshold, 60-99% of a paresthesia threshold, about 40% of a paresthesia threshold, about 60% of a paresthesia threshold, and about 80% of a paresthesia threshold. This allows the stimulation to effectively penetrate beyond Lamina I to active Lamina II to IV with minimal nerve root stimulation which produce paresthesia.

[0106] In one example, the electrodes may further include a pair of first and second electrodes. The first and second electrodes may be placed approximate a thoracic spine of the subject, across T8 and T9 of a thoracic spine of the subject, or across T9 and T10 of a thoracic spine of the subject. [0107] In one example, the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively. In this example, the first and second signals include a plurality of pulses and the pulses in the first signal have opposing polarities to pulses in the second signal. In one example, the first electrical signal may be a cathodic signal and the second signal may be an anodic signal in the sequence. The pair of electrodes with opposite polarities promotes effective stimulation of dendrites in the dorsal hom. In yet another example, the one or more electrodes includes any suitable combination of anodes and cathodes, either contiguous or spaced on an electrode array.

[0108] In one preferred example, the stimulation signals are cycled so that they are active for 34 seconds and inactive for 136 seconds (80/20 rule). The signals are applied to the T9/10 bipole, at 80% of perception threshold, and use 1000 psec Pulse Width. The signals can have a 100Hz frequency, or an average 100Hz target frequency, with stochastic variation of the frequency distributed about the target frequency. In another example, the frequency used includes a series of 17 alternating pulses above/below 100Hz in 0.25Hz increments, 98/102 up to 96/104 Hz (generating 4-8Hz) with time spent proportional to a Gaussian distribution to produce a theta band centred at 5.3Hz. Each set of frequencies is applied for lsec (random mix) then repeated once.

[0109] In general, a therapy using this approach will scale over time using 80% of perception threshold for the 1 ^st month, 60% of perception threshold for the 2 ^nd month, then 40% of perception threshold for the 3 ^rd month, with the patient being monitored to assess efficacy.

[0110] An example of the first and second electrical signals will now be described in more detail with reference to Figure 5.

[0111] A signal generator 130 is electrically connected to the connections 123, 124 and is configured to generate a sequence of first and second electrical signals that are applied to the first and second electrodes 121, 122, respectively.

[0112] As shown in Figure 5, a sequence Si of first and second electrical signals ESi, ES2 may be applied. The first and second electrical signals ESi, ES2 include a plurality of pulses P1-P16, and the pulses Pi-Ps in the first signal ESi have opposing polarities to pulses P9-P16 in the second signal ES2. In this example, the sequence Si of the first and second electrical signals ESi, ES2 has a period Ti. The pulses have a frequency f, a pulse width W and a magnitude of M.

[0113] In this example, in the sequence Si, the first electrical signal ESi is a cathodic signal and the second signal ES2 is an anodic signal. It should be appreciated that the first electrical signal may be an anodic signal and the second electrical signal may be a cathodic signal in the sequence. The sequence Si is configured to stimulate dendrites in the dorsal hom.

[0114] In this example, the magnitude M of the pulses P1-P16 is approximately 80% of paresthesia threshold. It should be appreciated that the magnitude of the pulses may vary in the sequence. In this example, the frequency f is about 100 Hertz, and the pulse width W is about lOOOps.

[0115] Accordingly, the system provides an arrangement for stimulating the dorsal hom in a biological subject, which effectively stimulate dendrites by providing sufficient charges to stimulate dendrites while minimising power required. The electrical signals may be able to swing over to the lateral aspect of the dorsal hom, and penetrate beyond Lamina I to active Lamina II-IV, so that dendrites are stimulated with limited nerve root stimulation and limited paresthesia being produced.

[0116] As previously mentioned, a range of different electrode arrangements can be used. For example, in one embodiment, the lead body includes at least two spaced apart outer electrodes and at least two spaced apart inner electrodes, with a respective connection being provided for each electrode. In another example, the lead body includes an electrode array having two spaced apart outer electrodes a plurality of spaced apart inner electrodes, and an example of this is shown in Figure 6, in which six electrodes are mounted on the lead body 611, with these including four inner electrodes 621 and two outer electrodes 622. Other arrangements including greater numbers of electrodes could be used, for example, including eight, ten, twelve, fourteen or sixteen electrodes.

[0117] In one example, where multiple electrodes are provided, these could have different functions. For example, therapy electrodes could be used to apply therapy signals to the subject, whilst other shielding electrodes, could be used to apply a shielding signal to shield surrounding tissue from the therapy signals. In this regard, the therapy and shielding signals typically have opposing polarities so that the shielding signals destructively interfere with the therapy signals, thereby reducing electric fields in tissue remote to the therapy electrodes. In one example, individual or inner electrodes 621 are typically therapy electrodes, whilst outer electrodes 622 are shielding electrodes, although this is not essential and other arrangements could be used.

[0118] The electrodes can have a variety of dimensions, and examples of this will now be described with reference to Figure 7.

[0119] In this example, four electrodes are shown, having respective lengths Li, L2, L3, L4, and separated by respective spacings Si, S2, S3. In this example, the lead body and hence electrodes are generally cylindrical, with a diameter Di.

[0120] In one example, the electrode lengths Li, L2, L3, L4, are less than 8.5mm, less than 9mm, less than 9.5mm, less than 10mm, less than 10.5mm, less than 11mm, less than 11.5mm, less than 12mm, greater than 1mm, greater than 1.5mm, greater than 2mm, greater than 2.5mm, greater than 3mm, about 3 -8mm, about 3mm, about 4mm, about 5mm, about 6mm, about 7mm, about 8mm. Inner and outer electrodes might have different lengths, so that /. _/ = l. ₄ > 1.2 = 1. ₃ . or Li — L4 < L2 =å3.

[0121] The electrode spacings Si, S2, S3 are typically less than 12mm, less than 10mm, less than 8mm, less than 6mm, less than 4mm, greater than 1mm, greater than 1.5mm, greater than 2.0mm, greater than 2.5mm, about 3 -4mm, about 3mm, about 4mm, about 3.3mm, about 3.4mm, and, about 3.5mm. Spacings may differ, so that the spacing between inner and outer electrodes differs to that between inner electrodes, such that .S' _/ = S ₃ > S2 or .S' _/ = S ₃ < S2.

[0122] An example of an internal structure of the lead is shown in Figure 8.

[0123] In this example, the lead body 811, includes an outer insulating layer 811.1, braided shield 811.2 inward of the outer insulating layer, an inner insulating layer 811.3 inside the braided shield 811.2 and one or more conducting fdars 811.4. A lumen open at a proximal end (not shown) may also be provided to allow for insertion of a stylet, as will be described in more detail below. [0124] In use, the conducting filars 811.4 provide the connections between the signal generator and the electrodes, whilst the inner and outer insulating layers 811.1, 811.3 provide electrical isolation from the subject, ensuring signals are transmitted to the electrodes. The braided shield 811.2 can be used to reduce the magnitude of stray electrical fields in the body either through grounding or the use of an active shielding signal.

[0125] The conducting filars 811.4 can be braided with at least one standard wire made of titanium alloys, such as MP35N, whilst the braided shield can be made from tantalum, which assist with heat dissipation, whilst maintaining flexibility and strength. The insulating layer(s) are typically made biomedical elastomers, thermoplastic polyether polyurethane, such as 55D polyurethane, or the like. These arrangements allow the lead body to be MRI compatible, which in turn allows MRI to be used to assist with lead positioning. The lead body can also be configured with tines and/or wings to mitigate migration within the body, once the lead is positioned.

[0126] As previously mentioned, the therapy signals are configured to stimulate or inhibit activity of the dorsal column, and in one example are applied to a dorsal column proximate a T9/T10 spinal region, including but not limited to T9/T10 dorsal column, as shown in Figure 3. To achieve this, the lead body is configured to be positioned in an anterolateral region of vertebrae, and may extend at least partially along or around vertebrae.

[0127] Once in position, the lead body is configured to extend from the dorsal column of vertebrae to the signal generator. In this regard the signal generator can be provided externally to the subject, but more typically is an implantable signal generator and an example of this is shown in Figure 9.

[0128] In this example, the signal generator 930 is implanted in a lower posterior of a torso of the subject 901, whilst the lead 910 extends to the dorsal column of vertebrae in the thoracic region 902 of the subject’s spine 903. Power can be supplied to the signal generator via an internal power supply. However, alternatively a separate power supply could be provided externally to the subject 901, and which is operatively coupled to the signal generator 930, via inductive coupling or similar.

[0129] An example signal generator arrangement is shown in more detail in Figure 10. [0130] In this example, the signal generator 1030 forms part of a controller 1036, which also includes an electronic processing device 1031 and a memory 1032, interconnected with the signal generator 1030 via a bus 1033, or other suitable arrangement. An external interface 1035 is provided, which is typically a wireless interface, such as Wi-Fi, Bluetooth or another short range wireless communications interface, to allow an external device, such as a computer system, smart phone or table, to be used to control the controller 1036.

[0131] In use, the electronic processing device 1031 executes instructions in the form of applications software stored in the memory 1032 to allow the required processes to be performed, and in particular to allow the signal generator to be controlled to thereby generate therapy and/or shielding signals, which are then applied to therapy and/or shielding electrodes 1021, 1022.

[0132] The applications software may include one or more software modules, and may be executed in a suitable execution environment, such as an operating system environment, or the like. The electronic processing device could be a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement.

[0133] In one example, the controller 1036 includes an internal power supply, allowing the controller 1036 to be fully subcutaneously implemented. In one example, the controller 1036 may include a receiving coil 1034 that is provided to allow power to be inductively received from a power supply 1040, for example, allowing this to be used to recharge the internal battery. In this regard, the power supply includes a processing device 1041, signal generator 1042, transmitting coil 1043 and battery 1044. The electronic processing device could be a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement.

[0134] The processing device 1041 controls the signal generator 1042 to apply a signal to the transmitting coil, allowing power to be inductively coupled to the controller 1035. This avoids the need for the lead or other physical connections to pass through the skin of the subject, whilst still allowing the battery to be recharged as needed. [0135] A further alternative is for the battery to be provided externally and used to drive an implanted controller via wired or wireless inductive connections. Thus, it will be appreciated that the control system and/or power supply can be external, implanted or a combination of the two.

[0136] In another example the power supply could include an input 1045, such as a touch screen or similar, which can be used to control operation of the system. In this regard, control inputs provided via the input 1045 could be detected by the processing device 1041 and used to modulate the inductive charging signal, which can in turn be detected by the processing device 1031, allowing this to be used to control operation of the signal generator. For example, this could be used to change the timing, magnitude, waveform, frequency, or other parameters of the generated therapy and/or shielding signals.

[0137] A study was performed to assess the effectiveness of the above described arrangements in treating neuropathic lower back pain. The study used Dorsal Horn Dendrite Stimulation, including signals at 100Hz, 1000ps pulse width, biphasic cathode/anode signals, and a square waveform. Signals were applied at 80%, testing at 60% and then 40% (20%) of perception threshold, with the patient selecting the preferred option. For the purpose of illustration, these protocols are referred to as "Subwave". The patient was also given the option to abort to pre existing therapies, referred to as "ND" and "Tonic", if needed.

[0138] A summary of the baseline characteristics of the patients is outlined in Table 1. In this regard, pain was assessed using VAS (visual analogue scale), BPI (brief pain inventory), and EQ-5D (EuroQol- 5 Dimension).

Table 1

[0139] A summary of the program used by each patient is outlined in Table 2.

Table 2

[0140] A summary of program preference is shown in Table 3 below.

Table 3

[0141] A summary of trial outcomes is shown in Table 4 below, with further detail being shown in Figures 11-13.

Table 4

*8 patients did not trial Subwave (pre-amendment)

†10 patients did not trial tonic (2 unable to capture pain / 3 preferred other programs / 5 tonic trial removed from protocol)

2 patients had no preference (failed trial)

[0142] It should be noted that square wave form was tested due to hardware limitations, but nevertheless demonstrated suitable efficacy. Specifically, results demonstrate efficacy and show improved outcomes for patients compared to existing best practice approaches.

[0143] Accordingly, the above approach provides a form of spinal cord stimulation that provides paresthesia free treatment that is free of problems normally associated with Dorsal Column stimulation and which allows for an extremely low energy consumption of energy. This provides improved outcomes compared to existing best practice and can avoid accommodation/tolerance, allowing this to be used on a long term basis. [0144] Throughout this specification and claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers or steps but not the exclusion of any other integer or group of integers. As used herein and unless otherwise stated, the term "approximately" means ±20%.

[0145] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a support” includes a plurality of supports. In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings unless a contrary intention is apparent.

[0146] It will of course be realised that whilst the above has been given by way of an illustrative example of this invention, all such and other modifications and variations hereto, as would be apparent to persons skilled in the art, are deemed to fall within the broad scope and ambit of this invention as is herein set forth.