Methods and devices for treating pain in a spinal cord injured patient

Abstract

Methods are provided for treating neuropathic pain in a patient by arranging an electrode in a region of a patient's spinal cord corresponding to a location of perceived pain according to a novel or non-classical somatotopic map, identifying one or more pain-generating DREZs in a patient based on measurable neuronal or neuroelectrical hyperactivity in the patient's DREZs and arranging an electrode in a region of the patient's spinal cord corresponding to the identified one or more pain-generating DREZs, and / or measuring neuronal or neuroelectrical hyperactivity in the patient's DREZs by performing a non-surgical or non-invasive technique to identify one or more pain-generating DREZs in the patient based on measurable neuronal or neuroelectrical hyperactivity in the patient's DREZs and arranging an electrode in a region of the patient's spinal cord corresponding to the identified pain-generating DREZs. An electric signal is applied to the electrode to treat the patient's neuropathic pain.

Description

Methods and Devices for Treating Pain in a Spinal Cord Injured PatientCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 63 / 572,738 filed April 1 , 2024, the content of which is incorporated by reference herein in its entirety.FIELD

[0002] The disclosure is directed to methods and devices for treating (i.e. , alleviating, reducing, diminishing, or otherwise attenuating) pain in a patient (e.g., sympathetically mediated neuropathic pain in a spinal cord injured patient) by arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain according to a novel or non-classical somatotopic map.BACKGROUND

[0003] Spinal cord injury (SCI) frequently results in severe or disabling pain. Individuals with a SCI suffer anywhere from between 20 and 77% incidence of some level of severe or disabling chronic pain. Davis et al., Clin Orthop 112:76-80 (1975); Richards et al., Pain 8:355-366 (1980); Siddall et al., Spinal Cord 39:63-73 (2001); Stormer et al., Spinal Cord 446-455 (1997); Woolsey, J Am Paraplegia 9:39-41 (1986). Patients suffering from at least some level of severe or disabling chronic pain show reduced rehabilitation potential and tend to have a significant overall reduction in quality of life.

[0004] Central neuropathic pain has proven notoriously difficult to treat, often proving recalcitrant to modern medical and surgical pain treatment procedures. Surgical treatment of specific DREZ(s) of the spinal cord are of particular interest. Surgical treatment of a central neuropathic pain generating DREZ is believed to disrupt the neural, i.e., electrical, communication and / or generation of aberrant pain signals that result from the injury. Initially, empirical techniques have been used to target DREZ sites for surgical treatment, resulting in modest outcomes for the patient, i.e., DREZ sites proximate to the site of injury targeted for treatment. Friedman et al., J Neurosurg 65:465-469 (1986); Ishijima et al., Appl Neurophysiol 51 :2-5, 175-187 (1988); Rath et al., Acta Neurochir 138:4, 364-369 (1996); Rath et al., Sterotact Funct Neurosurg 68:1-4, Pt 1 , 161-167 (1997). One of the more relevant patient studies using this empirical technique suggests that approximately 50% of patients so treated achieve good relief from SCI associated pain. Friedman et al., J Neurosurg 65:465- 469 (1986). In that series, at-level pain, i.e., pain at the immediate vicinity of the injury, responded best (74% “good results”) and below-level pain, i.e., pain below the level of injury, responded poorly (20% “good results”).

[0005] Spinal cord injury pain can be mediated through the sympathetic nervous system. Specifically, hyperactive electrical neuronal signals originating in the DREZ of the spinal cord above (cephalad) and / or below (caudal) the level of injury can ascend to brain pain centers through afferent sympathetic sensory pathways within the spinal cord and / or with aid of the sympathetic chain, routing around the injury site to reach brain pain centers. The pain may be perceived as below the neurological level of spinal cord injury, where it should not be perceived. For example, in a complete spinal cord injury at the neurological level of T10, a patient should not feel pain below (caudal to) the umbilicus. However, the patient can nevertheless perceive pain in these regions. The pain can be generated by tissues located below (caudal to) the level of spinal cord injury and / or above (cephalad to) the level of spinal cord injury. Such sympathetically mediated spinal cord injury pain is perceived by the patient to be below the neurological level of spinal cord injury (referred to herein as “below- level pain”).

[0006] In some instances, conventional electrodes used to treat pain (e.g., pain resulting from spinal cord injury) can be of an insufficient length to span an entire area of sympathetically mediated pain, such as that caused by hyperactivity in a patient’s DREZs. In addition, conventional electrodes also may not span an entire length of one or more paingenerating DREZs.

[0007] There remains a need for developing methods and devices for treating (i.e., alleviating, reducing, diminishing, or otherwise attenuating) pain in a patient (e.g., pain generated by spinal cord tissue caudal to a level of a spinal cord injury), such as by addressing all spinal cord regions of neuropathic pain generation by providing one or more electrodes to treat pain that are of a sufficient length to span an entire area of sympathetically mediated pain, such as that caused by hyperactivity in a patient’s DREZs, and / or to span an entire region (e.g., one or more locations) of perceived pain in the patient according to a novel or non-classical somatotopic map, thereby treating patient’s pain using one or more electrodes of sufficient length and in particularly desirable regions of the spinal cord.BRIEF SUMMARY

[0008] Methods and devices are provided for treating neuropathic pain in a patient. One or more electrodes can be disposed or arranged on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain, according to a novel or non-classical somatotopic map. An electric signal can be applied to the electrode to treat the neuropathic pain in the patient.

[0009] In some aspects, the patient is a spinal cord injured patient. In other cases, thepatient is a non-spinal cord injured patient.

[0010] In a first aspect, a method for treating neuropathic pain in a patient includes: arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain according to a novel or non- classical somatotopic map; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

[0011] In another aspect, a method for treating neuropathic pain in a patient includes: identifying one or more pain-generating DREZs in the patient based on measurable neuronal or neuroelectrical hyperactivity in the patient’s DREZs; arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to the identified one or more pain-generating DREZs; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

[0012] In another aspect, a method for treating neuropathic pain in a patient includes: measuring neuronal or neuroelectrical hyperactivity in the patient’s DREZs by performing a non-surgical or non-invasive technique to identify one or more pain-generating DREZs in the patient based on measurable neuronal or neuroelectrical hyperactivity in the patient’s DREZs; arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to the identified one or more pain-generating DREZs; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

[0013] In another aspect, a device includes: an electrode configured to be arranged on the dura covering spinal cord tissue in a region of the patient’s spinal cord; and a stimulation generator configured to deliver an electric signal to the electrode to treat neuropathic pain in the patient, wherein the electrode spans an entire length of all pain-generating DREZs in the patient identifiable based on measurable neuronal or neuroelectrical hyperactivity in the patient’s DREZs.

[0014] In another aspect, a device includes: an electrode configured to be arranged on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain according to a novel or non-classical somatotopic map; and a stimulation generator configured to deliver an electric signal to the electrode to treat neuropathic pain in the patient.

[0015] Additional variations and features are set forth in part in the description that follows, and will become apparent to those skilled in the art upon examination of the specification or can be learned by the practice of the disclosed subject matter. A further understanding of the nature and advantages of the disclosure can be realized by reference to the remaining portions of the specification and the drawings, which form a part of this disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The description will be more fully understood with reference to the following figures and data graphs, which are presented as variations of the disclosure and should not be construed as a complete recitation of the scope of the disclosure, wherein:

[0017] FIG. 1 illustrates a flow diagram of a method for treating neuropathic pain in a patient according to an illustrative variation;

[0018] FIG. 2A illustrates a dermatomal chart alongside a representation of the corresponding regions of the spinal cord according to an illustrative variation;

[0019] FIG. 2B is a table illustrating a novel or non-classical somatotopic map for mapping a location of a patient’s perceived pain to a region of the patient’s spinal cord;

[0020] FIG. 2C is a table illustrating a classical map for mapping a location of a patient’s perceived pain to a region of the patient’s spinal cord;

[0021] FIG. 2D illustrates another dermatomal chart alongside a representation of the corresponding regions of the spinal cord according to an illustrative variation;

[0022] FIG. 3A illustrates a device for treating neuropathic pain in a patient according to an illustrative variation;

[0023] FIG. 3B illustrates a top view of a device for treating neuropathic pain in a patient according to an illustrative variation;

[0024] FIG. 3C illustrates a device for treating neuropathic pain in a patient according to an illustrative variation;

[0025] FIG. 3D illustrates a top view of a device for treating neuropathic pain in a patient according to an illustrative variation;

[0026] FIG. 3E illustrates the device of FIG. 3A in use by being arranged in a region of the patient’s spinal cord corresponding to a location of perceived pain according to an illustrative variation;

[0027] FIG. 3F illustrates the device of FIG. 3C in use by being arranged in a region of the patient’s spinal cord corresponding to a location of perceived pain according to an illustrative variation;

[0028] FIG. 3G illustrates bony vertebrae levels of a patient’s spinal cord with the device of FIG. 3C in use by being arranged in a region of the patient’s spinal cord corresponding to perceived pain in the patient’s lower extremities based on the novel or non-classical somatotopic map of FIG. 2B according to an illustrative variation;

[0029] FIG. 3H illustrates bony vertebrae levels of a patient’s spinal cord with the device of FIG. 3C in use by being arranged in a region of the patient’s spinal cord corresponding to perceived pain in the patient’s rectal, gluteal, and / or genitalia regions based on the novel or non-classical somatotopic map of FIG. 2B according to an illustrative variation;

[0030] FIG. 3I illustrates bony vertebrae levels of a patient’s spinal cord with the device ofFIG. 30 in use by being arranged in a region of the patient’s spinal cord corresponding to perceived pain in the patient’s trunk based on the novel or non-classical somatotopic map of FIG. 2B according to an illustrative variation; and

[0031] FIG. 4 illustrates a perspective cutaway view of a spinal cord at or immediately cephalad or caudal the level of SCI according to an illustrative variation.DETAILED DESCRIPTION

[0032] The disclosure can be understood by reference to the following detailed description, taken in conjunction with the drawings as described below. It is noted that, for purposes of illustrative clarity, certain elements in various drawings can not be drawn to scale.

[0033] “Dorsal root entry zone” (DREZ) refers to the area of the dorsal gray matter of the spinal cord in the region of the dorsal roots for a particular region of the spinal cord. For purposes of the present disclosure, a DREZ includes any portion of the entry zone area from the dorsal surface of the spinal cord where the roots enter to a depth of at least rexed laminae V and VI. Some variation exists in the structure of a particular DREZ dependent on the region of the spine through which it passes, and such variations are well-known to those skilled in the art and are within the scope of the present disclosure. At each region of the spinal cord, there exists both a right-side and a left-side DREZ; unless specified, as used herein, the term DREZ treats the right and left DREZs interchangeably. In addition, the electrical activity in the left and right DREZs at a particular level do not necessarily have to be symmetrical (i.e., one side can show neuroelectrical hyperactivity and the other shown normal neuroelectrical activity).

[0034] “Treating pain” refers to performing the methods described herein to decrease in the level of perceived pain in a patient.

[0035] “At-level pain” refers to pain that is perceived in a segmental pattern within a dermatome of the neurological level of injury or within three dermatomes below the neurological level of injury. FIG. 2A and FIG. 2D illustrate dermatomal charts alongside a representation of the corresponding regions of the spinal cord.

[0036] “Below-level pain” refers to pain that is perceived more than three dermatomes below the neurological level of injury. FIG. 2A and FIG. 2D illustrate dermatomal charts alongside a representation of the corresponding regions of the spinal cord.

[0037] “Pain-generating DREZ” refers to any DREZ involved in the generation or communication of pain signals resultant from a SCI. Typically, a pain-generating DREZ, as compared to a non-pain-generating DREZ (also referred to as a “cold” DREZ; refer to electrically normal “Cold Tissue” in FIG. 4), involves neuronal hyperactivity and / or hyperexcitability that can be measured / identified in accordance with the techniques of thepresent disclosure (also referred to as a “hot” DREZ; refer to electrically hyperactive “Hot Tissue” in FIG. 4).

[0038] All vertebrate animals have a central axis of the body that consists of the spinal or vertebral column. The vertebral column consists of a number of connected irregular bones, termed the vertebrae, which surround and thereby protect a spinal cord. The vertebrae also support the weight of the trunk and transmit the weight to the lower limbs.

[0039] The vertebrae are grouped according to the region in which they lie — cervical, thoracic, lumbar, sacral and coccygeal or caudal. Each vertebrae has a ventral and dorsal side. In series with each vertebrae are a number of spinal nerves. Each nerve is formed by the union of an anterior (motor) and posterior (sensory) nerve-root. The posterior or dorsal nerve-roots are the central branches of the axons of the pseudounipolar cells of the spinal ganglia. There are thirty-one pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal.

[0040] Injury to nerves often results in persistent pain. Often this pain is described as severe, diffuse and continuous with periods of exacerbation. It is widely accepted that injury to a nerve often results in the abnormal up-regulation of neuronal activity and that this upregulation plays a key role in pain associated with the injury. Several electrophysiological studies have suggested that damaged nerves show abnormal changes in their firing pattern, including spontaneous hyperactivity with the DREZ. Falci, S. et al., J. Neurosurgery Spine (2002); Falci, S. et al., J. Neurosurgery Spine (2018).

[0041] SCI below-level neuropathic pain is a difficult condition to treat both pharmacologically and surgically. Successful treatment using surgically created lesions of the spinal cord DREZ, guided by intramedullary monitoring of neuronal electrical hyperactivity, has shown that DREZs both cephalad and caudal to the level of injury can be the primary generators of SCI below-level pain, that below-level pain perception follows a novel somatotopic map of pain-generating DREZs (also referred herein as a non-classical map for treating sympathetically mediated neuropathic pain), and that neuronal transmission to brain pain centers can occur primarily through sympathetic nervous system (SNS) pathways.

[0042] Methods and devices for treating (i.e., alleviating, reducing, diminishing, or otherwise attenuating) pain in a patient (e.g., sympathetically mediated pain in a spinal cord injured patient) are described herein, such as by arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain according to a novel somatotopic map and applying an electric signal to the electrode to treat the neuropathic pain in the patient. The spinal cord tissue can include any cell type (neuronal or glial) and / or one or more DREZs.

[0043] In some variations, the pain can be described as physical pain, burning, searing,sharp, electrical, stabbing, pins-and-needles, frostbite, tearing, ripping, heat, and / or cold, including combinations thereof. The perceived pain may, in some variations, be pain, squeezing, tight, and / or pressure, including combinations thereof. In additional variations, the pain can be perceived below the neurological level of injury. In some variations, the pain can be perceived both at and below the neurological level of injury. In additional variations, pain-generating spinal cord tissue can originate below, at, and / or above the level of the location of spinal cord injury.

[0044] FIG. 1 illustrates a flow diagram of a method for treating pain in a patient according to an illustrative variation. The method can include obtaining the history of the patient (e.g., type and location of pain, prior steps taken to non-surgically treat pain) prior to performing any of the steps illustrated in FIG. 1.

[0045] At step 110, an electrode is disposed or arranged on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain and / or pain sensitivity (hereinafter “perceived pain” for short) according to a novel somatotopic map (also referred herein as a non-classical map for treating sympathetically mediated neuropathic pain). The location of perceived pain can be correlated to a location of one or more pain-generating DREZs according to the novel somatotopic map. In some variations, the novel somatotopic map can suggest the potential for neuroelectrical hyperactivity caudal to the level of injury in the patient.

[0046] In one non-limiting example, if the pain is generated by spinal cord tissue caudal to a level of the spinal cord injury, the electrode can generally be arranged below a level of the spinal cord injury. In another non-limiting example, if the pain is perceived by the patient to be below a neurological level of the spinal cord injury, the electrode can generally be arranged below a level of the spinal cord injury. In another non-limiting example, if the pain is perceived by the patient to be below a neurological level of the spinal cord injury, the electrode can generally be arranged above a level of the spinal cord injury.

[0047] In variations, the spinal cord tissue implicated in perceived pain is determined by comparing the anatomical location of the patient’s perceived pain to a novel somatotopic map of SCI pain-generating spinal cord tissue and / or pain-generating DREZs. Step 110 can include identifying a first location of perceived pain in the patient, mapping the first location of perceived pain to a first mapped region of the spinal cord according to the novel somatotopic map, and arranging the electrode in the first mapped region. In variations, step 110 can include mapping the level of injury and the regions of perceived pain in the patient against a novel somatotopic map prepared in accordance with the present disclosure. In such variations, the identification of one or more pain-generating DREZs in a patient can be based on correlating the patient’s perceived pain (and location of injury) with DREZs identified in other patients having similar types of pain and locations of injury. For example,pain (e.g., foot, leg, rectal, gluteal, and / or genitalia) in the patient can be correlated with predetermined potential hyperactive DREZ sites (e.g., T10, T11 , T12, L1) found through mapping in other patients. The novel somatotopic map can correspond to data from a plurality of spinal cord injured patients. In variations, the novel somatotopic map can provide a “standard curve,’’ where the location of a patient’s pain can be correlated to a standardized potential pain-generating DREZ site. Data from patients for use in preparing the novel somatotopic map can have had localized perceived pain that corresponded to localized and measured hyperactive DREZs. A determination of DREZ hyperactivity can be conducted for each patient. In a non-limiting example, DREZ hyperactivity can be determined using a non- surgical and / or non-invasive technique. By way of non-limiting example, DREZ hyperactivity can be determined directly or indirectly using spectral markers of proteins indicative of DREZ hyperactivity.

[0048] Using data provided by the illustrative novel somatotopic map, pain occurring distal from an injury site (below-level pain) can be mediated significantly by the sympathetic nervous system. Anatomic regions of perceived pain can be somatotopically mapped to specific DREZ segments of the spinal cord. Spinal cord caudal to the level of a completely transected spinal cord (the neurological injury) can be a source of below-level spinal cord injury neuropathic pain, and, in some cases, essentially a sole source. Further, below-level SCI pain transmission can be substantially through the sympathetic chain and SNS- mediated pain pathways. Novel or non-classical somatotopic maps prepared using the methods described herein, as well as the illustrative novel or non-classical somatotopic map of the present disclosure, can be used alone or in combination with evoking and / or measuring neuroelectrical hyperactivity to identify one or more pain-generating DREZs. In variations, evoked and / or measured neuroelectrical hyperactivity and novel somatotopic mapping are compared to identify one or more target pain-generating DREZs in a patient in preparation for treating the identified one or more pain-generating DREZs.

[0049] In some variations, a patient can perceive below-level pain that follows a novel somatotopic map of DREZ hyperactivity (also referred herein as a non-classical map for treating sympathetically mediated neuropathic pain). For example, spinal cord pain can be perceived by a patient (e.g., in step 102) to be caudal to a level of a spinal cord injury and / or below a neurological level of the spinal cord injury. In such cases, in step 110, the electrode can be arranged below a level of the spinal cord injury. In variations, the electrode can span an entire length of all pain-generating DREZs as identified according to the novel somatotopic map. In variations, step 110 can include mapping a location of a patient’s perceived pain to a mapped region of the patient’s spinal cord according to a novel or non- classical somatotopic map, such as is shown in the novel or non-classical somatotopic map 210 illustrated in FIG. 2B, and arranging the electrode in the mapped region to treat thepatient’s neuropathic pain, such as is shown in FIGS. 3G-3I, which illustrate bony vertebrae levels of the patient’s spinal cord as described herein.

[0050] By way of non-limiting example, if a patient perceives pain in a lower extremity (i.e., the legs and / or feet), such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T11 to L1 regions of the patient’s spinal cord. After such mapping according to the novel or non- classical somatotopic map, the electrode can be arranged between at least the T11 and L1 regions including, in variations, arranging the electrode to span the entirety of at least the T11 to L1 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3G, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of the DREZs of at least the T11 to L1 regions of the patient’s spinal cord 318. Although the spinal cord leads 317A, 317B are illustrated as those of the device of FIG. 3C, it will be appreciated that any alternative number and / or pattern of spinal cords leads could be employed, including but not limited to the lead 317 of FIG. 3A, the paddle 330 of FIG. 3B, the paddle 330 of FIG. 3D, or the like, including combinations thereof.

[0051] By way of further non-limiting example, if a patient perceives pain in the rectal, gluteal, and / or genitalia regions, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T8 to T10 regions of the patient’s spinal cord. After such mapping according to the novel or non-classical somatotopic map, the electrode can be arranged between at least the T8 and T 10 regions including, in variations, arranging the electrode to span the entirety of at least the T8 to T10 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3H, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of the DREZs of at least the T8 to T10 regions of the patient’s spinal cord 318. Although the spinal cord leads 317A, 317B are illustrated as those of the device of FIG. 3C, it will be appreciated that any alternative number and / or pattern of spinal cords leads could be employed, including but not limited to the lead 317 of FIG. 3A, the paddle 330 of FIG. 3B, the paddle 330 of FIG. 3D, or the like, including combinations thereof.

[0052] By way of another non-limiting example, if a patient perceives pain in the trunk, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T3 to T7 regions of the patient’s spinal cord. After such mapping according to the novel or non-classical somatotopic map, the electrode can be arranged between at least the T3 and T7 regions including, in variations, arranging the electrode to span the entirety of at least the T3 to T7 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3I, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of the DREZs of at least the T3 to T7 regions of the patient’s spinal cord 318. Although thespinal cord leads 317A, 317B are illustrated as those of the device of FIG. 3C, it will be appreciated that any alternative number and / or pattern of spinal cords leads could be employed, including but not limited to the lead 317 of FIG. 3A, the paddle 330 of FIG. 3B, the paddle 330 of FIG. 3D, or the like, including combinations thereof.

[0053] Illustrative examples of step 110 include: if a patient presents with pain in the trunk, the mapping data shows that the potential pain-generating DREZs will map between and / or from at least T3 and T7 (e.g., DREZ hyperactivity in at least T3 to T7 spinal cord regions can result in truncal below-level pain); if a patient presents with pain in the rectal, gluteal, and / or genitalia regions, the mapping data shows that the potential pain-generating DREZs will map between and / or from at least T8 and T10 (e.g., DREZ hyperactivity in at least T8 to T10 spinal cord regions can result in rectal, gluteal, and / or genitalia below-level pain); and if a patient presents with pain in the legs and feet, the mapping data shows that the potential pain-generating DREZs will map between and / or from at least T 11 and L1 (e.g., DREZ hyperactivity in at least T11 to L1 spinal cord regions can result in leg and / or foot below-level pain). In this regard, the novel somatotopic mapping described herein can be used to identify one or more below-level pain-generating DREZs. Mediation of DREZ hyperactivity through classical pain pathways (e.g., according to the classic mapping described herein) can lead to at-level pain, and if hyperactivity is mediated through the sympathetic nervous system, pain can be perceived below-level in regions described by the novel somatotopic map described herein. The novel somatotopic map may, in variations, be developed from reported locations of perceived pain from patients and / or measured neuroelectric hyperactivity.

[0054] Prior work has also implicated the SNS, demonstrating the development and novel dermatomal locations of electrically hyperactive PGM neuronal regions causative of SCI neuropathic pains and the novel somatotopic spinal cord mapping of the hyperactive posterior grey matter (PGM) correlative with interomediolateral (IML) cell-column end organ innervation of body regions of perceived pain. In patients with complete spinal cord injuries and prior surgical spinal cord transections, excellent below-level pain relief with DREZ surgery performed only caudal to the transections has been achieved, supportive of a SNS mediation of DREZ electrical hyperactivity to brain pain centers, inclusive of the sympathetic chain, and the novel somatotopic map of pain-generating DREZs.

[0055] Deafferentation of the DREZ(s) subsequent to SCI can cause development of electrically hyperactive second order pain sensory neurons within the DREZ(s), cephalad, at, and caudal to the level of complete SCI, which can then become primary generators of below-level pain, pain perception dictated by a novel somatotopic map of IML cell column end organ innervation, implicating involvement of the SNS.

[0056] The method can include optional steps before or after step 110.

[0057] The methods can optionally include alternative steps of testing the location of perceived pain and / or measuring neuroelectric hyperactivity in the patient.

[0058] In one optional alternative, method 100 can include a step 102 of testing a location of perceived pain on a patient. Step 102 may, in variations, include stimulating the location of perceived pain (e.g., by touch, pressure, applying heat, applying cold, or applying electrical stimulus, among other methods). In variations, the electrode can be configured to stimulate all DREZ generating all locations of perceived pain on the patient (e.g., according to a novel somatotopic map). In some variations, the perceived pain may include pain and / or pressure (e.g., physical pain, burning, searing, sharp, electrical, stabbing, pins-and- needles, frostbite, tearing, ripping, heat, and / or cold, including combinations thereof), although those skilled in the art will recognize that other descriptors of perceived pain are possible and are envisioned within the scope of the present disclosure.

[0059] The method 100 can optionally include a step 112 of arranging another electrode (e.g., a second electrode 316) on the dura covering tissue in a region of the spinal cord 318 associated with a location of perceived pain (e.g., a second region of the spinal cord associated with a second location of perceived pain) according to a classical pain map. Step 112 can include identifying a second location of perceived pain in the patient, mapping the second location of perceived pain to a second mapped region of the spinal cord according to the classical map, and arranging the electrode in the second mapped region. In variations, step 112 can include mapping the level of injury and the regions of perceived pain in the patient against a classical map. In such variations, the location of perceived pain in the classical map can be correlated to a location of one or more pain-generating DREZs. In variations, the electrode(s) can advantageously be of a sufficient length to span both the location(s) identified according to the novel or non-classical map (e.g., as illustrated in FIG. 2B) as well as the location(s) identified according to the classical map (e.g., as illustrated in FIG. 2C), although other variations are not necessarily so limited.

[0060] Step 112 (arranging an electrode on a location of the dura corresponding to a classical pain map) can occur before, after, or simultaneously with step 110 (arranging an electrode on a location of the dura corresponding to the novel somatotopic pain map).

[0061] In variations, the electrode can span an entire length of all pain-generating DREZs as identified according to the classical map. In variations, step 112 can include mapping a location of a patient’s perceived pain to a mapped region of the patient’s spinal cord according to a classical map, such as is shown in the classical map 220 illustrated in FIG. 2C, and arranging the electrode in the mapped region to treat the patient’s pain. By way of non-limiting example, if a patient perceives pain in a lower extremity (i.e., the legs and / or feet), such perceived pain location can be mapped from the L1 to S1 or L2 to S1 regions of the patient’s spinal cord. After such mapping, the electrode can be arranged between the L1and S1 or L2 and S1 regions including, in variations, arranging the electrode to span the entirety of the L1 to S1 or the L2 to S1 regions of the patient’s spinal cord, to treat the patient’s pain. By way of further non-limiting example, if a patient perceives pain in the rectal, gluteal, and / or genitalia regions, such perceived pain location can be mapped from the S2 to S5 regions of the patient’s spinal cord. After such mapping, the electrode can be arranged between the S2 and S5 regions including, in variations, arranging the electrode to span the entirety of the S2 to S5 regions of the patient’s spinal cord, to treat the patient’s pain. By way of another non-limiting example, if a patient perceives pain in the trunk, such perceived pain location can be mapped from the T2 to T12 regions of the patient’s spinal cord. After such mapping, the electrode can be arranged between the T2 and T12 regions including, in variations, arranging the electrode to span the entirety of the T2 to T12 regions of the patient’s spinal cord, to treat the patient’s pain.

[0062] Generally, the second mapped region (according to the classical map) can be different from the first mapped region (according to the novel somatotopic map). Illustrative examples of step 112 include: if a patient presents with pain in the trunk, the mapping data can show that the potential pain-generating DREZs will map between T2 and T12; if a patient presents with pain in the rectal, gluteal, and / or genitalia regions, the mapping data can show that the potential pain-generating DREZs will map between S2 and S5; and if a patient presents with pain in a lower extremity (i.e., the legs and / or feet), the mapping data can show that the potential pain-generating DREZs will map between L1 and S1 or L2 and S1.

[0063] In studies, patients who experienced pain in the rectal, gluteal, and / or genitalia regions had the presence of DREZ hyperactivity recorded in spinal cord segments T8, T9, and T10. These findings contrast with classical spinal dermatomes (e.g., compare FIG. 2B and FIG. 2C) but are consistent with the novel somatotopic map of sympathetically mediated below-level pain-generating DREZs and end organ innervation of the IML cell column. Studies have shown that DREZ neuronal hyperactivity occurring and restricted to dermatomal levels T8-T10 can be sufficient to generate below-level pain in the entirety of the rectal, gluteal, and / or genitalia regions. In such studies, patients had no DREZ hyperactivity recorded caudal to S1 , in sacral dermatomes classically mediating pain in these same regions, although some patients had DREZ hyperactivity recorded at T9 and T10 spinal cord levels and at-level pain truncal pain experienced at these same T9 and T10 dermatomal levels, consistent with classical somatotopic sensory mapping and spinothalamic mediation of at-level pain.

[0064] After arranging the electrode(s) on the dura covering spinal cord tissue in the region of the patient’s spinal cord corresponding to the location of perceived pain according to the novel somatotopic map (step 110) and / or the classical map (step 112), the method100 includes a step 120 of applying an electrical signal to the electrode(s) to treat the pain in the patient. The electrode(s) can generally be configured to deliver electrical stimulation to one or more of the patient’s DREZs, such as to reduce the patient’s perceived pain. The electrical stimulation delivered by the electrode(s) can generally be chosen as desired to suit a particular application, such as in the form of electrical stimulation pulses and / or continuous electrical stimulation waveforms. By way of non-limiting example, the electrical stimulation delivered by the electrode(s) can be characterized by controlled voltage and / or current levels, pulse width, pulse rate, pulse burst rate, and / or pulse burst duration.

[0065] In another optional alternative, method 100 can include a step 105 of measuring neuroelectric hyperactivity on the patient (e.g., in the patient’s DREZs). The method 100 can further include an optional step 108 of identifying one or more pain generating DREZs in the patient based on measurable neuroelectrical hyperactivity in the patient’s DREZs.Measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may, in some variations, include exposing the patient’s spinal cord (e.g., opening the dura matter of the spinal cord) and identifying DREZs of the segments. By way of non-limiting example, analysis of the DREZs (e.g., electrophysiological analysis) can be performed, beginning with the DREZs at the level of injury and proceeding through all levels cephalad.

[0066] Measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may, in other variations, include non-surgical and / or non-invasive techniques. By way of non-limiting example, measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may include the use of the classical map described herein.

[0067] Measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may, in yet other variations, include other non-surgical and / or non-invasive techniques. By way of non-limiting example, measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may include the use of remote spectral sensing, functional magnetic resonance imaging (fMRI), a positron emission tomography (PET) scan, magnetoencephalography (MEG), current perception threshold testing, or the like, including combinations thereof. In variations, measuring and / or identifying neuroelectrical hyperactivity in the patient’s DREZs may include a combination of surgical and non-surgical and / or non-invasive techniques.

[0068] The determination of potential neuroelectrical hyperactivity in the DREZs may, in variations, employ the use of a novel somatotopic map as described herein. Data from a target DREZ can be interpreted by activity to identify neuroelectrical hyperactivity in the DREZ. Recordings of any neuroelectrical hyperactivity in the DREZ can be guided by a novel somatotopic map, as described herein. Those skilled in the art could establish any suitable parameters for measuring neuroelectrical hyperactivity in the patient’s DREZs, such as those described in commonly-owned U.S. Patent No. 8,694,107, which is herebyincorporated by reference herein for all purposes.

[0069] As an optional alternative, method 100 can include an optional step 122 of modifying one or more pain-generating DREZs in the patient (i.e., all pain-generating DREZs identified in step 108). In some variations, the one or more pain-generating DREZs can be modified and / or destroyed. In variations, the one or more pain-generating DREZs can be modified and / or destroyed using a surgical technique, such as microcoagulation, lesioning, ablation, and / or resection. In variations, modifying and / or destroying the one or more paingenerating DREZs can be performed cephalad and / or caudal to the level of injury.

[0070] In variations, method 100 can include an optional step 130 of administering a neuropathic pain drug to the patient. In variations, expressed proteins (e.g., determined by acquiring and comparing tissue from pain-generating and non-pain-generating DREZs) may be used as marker of spinal cord injury pain, and the neuropathic pain drug may be selected to target such expressed proteins. In variations, the neuropathic pain drug may act by binding to synaptic vesicle glycoprotein 2A (SV2A). In variations, the neuropathic pain drug can be a 2-oxo-pyrrolidin-1-yl bytanamide derivative. In variations, the neuropathic pain drug can be gabapentin, pregabalin, levetiracetam, brivaracetam, or the like, including combinations thereof. In variations, the neuropathic pain drug can be administered intrathecally, including below the level of the spinal cord injury. The neuropathic pain drug and techniques for selecting and / or administering the neuropathic pain drug to a patient are more fully described in commonly-owned U.S. Patent No. 11 ,596,596, which is hereby incorporated by reference herein for all purposes.

[0071] As will be appreciated by those skilled in the art, individual steps of method 100 illustrated in the flow diagram of FIG. 1 or aspects thereof may be combined with any other one or more steps of method 100 or aspects thereof, and the above-described implementation is not intended to and does not in any way limit the scope of the present disclosure. Therefore, it is to be understood that although some aspects may be shown or described to illustrate the use of the present disclosure in the context of functional segments, such aspects may be combined with one another in any way and / or may be omitted from the scope of the present disclosure as desired to suit a particular application without departing from the spirit of the present disclosure as defined in the appended claims.

[0072] As will be appreciated by those skilled in the art, the methods described herein are generally not limited to any specific type and / or number of devices or electrodes. Devices are provided for performing the novel methods for treating pain according to any variation described herein. Those skilled in the art will appreciate that such a device can be any device known in the art for treating pain by providing electrical stimulation to a patient’s spinal cord. By way of non-limiting example, the devices could be implantable medical leads as described in U.S. Patent No. 8,204,607 and / or U.S. Patent No. 8,588,914, each of whichis incorporated by reference herein. Those skilled in the art will likewise appreciate that any of the foregoing devices can generally be employed for performing the novel methods for treating pain according to any variation described herein.

[0073] FIG. 3A illustrates a device for treating neuropathic pain in a patient according to an illustrative variation. In one variation, the device 300 can be configured to deliver electric stimulation to a patient 312 via one or more electrodes (e.g., located on one or more surfaces of one or more leads 316, 317). In the variations illustrated in FIG. 3C and FIGS. 3E-3I, the device 300 can include dual spinal cord leads 317A, 317B configured for arrangement on opposing sides of the patient’s spinal cord (e.g., on respective left-side and right-side DREZs, such that the dual spinal cord leads 317A, 317B substantially or completely span a width of the patient’s spinal cord), although other variations are not so limited. For example, in one variation as illustrated in FIG. 3E, a spinal cord lead 317 comprising one or more electrodes can be employed and arranged over or proximate the longitudinal midline of the patient’s spinal cord 318, although other variations are not so limited. In another variation as illustrated in FIG. 3F, a dual spinal cord leads 317A, 317B each comprising one or more electrodes can be employed and arranged such that a first spinal cord lead 317A is arranged more laterally relative to the longitudinal midline of the patient’s spinal cord 318 and a second spinal cord lead 317B is arranged more medially relative to the longitudinal midline of the patient’s spinal cord 318, although other variations are not so limited. As described herein, the spinal cord lead(s) 317 can generally include any number or arrangement of electrodes, such as to specifically provide a sufficiently long and / or wide electrode arrangement to apply an electrical signal to desired regions of the patient’s spinal cord.

[0074] As described herein, the electrode is generally configured to be arranged on the dura covering spinal cord tissue in a region of a patient’s spinal cord 318, such as in a region 319 in which the patient 312 experiences pain and / or the patient perceives pain. As further described herein, in variations, such as is illustrated in FIG. 3A, the electrode can span an entire length of all pain-generating DREZs 318A in the patient identifiable based on measurable neuroelectrical hyperactivity in the patient’s DREZs. The device further includes a stimulation generator (e.g., one or more voltage and / or current pulse generators) configured to deliver an electrical signal to the electrode for treating the pain in the patient. Other well-known aspects of the device (e.g., processors, power sources) will be readily apparent to those skilled in the art and are not otherwise described herein.

[0075] The electrode can generally be chosen as desired to suit a particular application, such as any electrode suitable for spinal cord stimulation. As will be appreciated by those skilled in the art, the term “electrode” is used herein to refer to a set of electrodes, with the term “set” being used in its mathematical sense to define a plurality of electrodes or singleelectrode (e.g., a unit set or singleton). In variations, such as is illustrated in FIG. 3B, the electrode can be a plurality of electrodes 334A-H that form an electrode array (e.g., rows, columns, and / or other patterns) on a paddle 330 or cylindrical lead. In the variation illustrated in FIG. 3D, a first set of electrodes 334A-D are arranged in a first column, and a second set of electrodes 334E-H are arranged in a second column (e.g., offset from one another by about 3.5-4 mm), such that the first and second sets of electrodes substantially or completely span a width of the patient’s spinal cord, although other variations are not so limited. By way of non-limiting example, the paddle lead 330 can carry an array of electrodes 334A-H on a body 332 thereof, which can be arranged as surface electrodes, ring electrodes, protrusions, or the like. By way of further non-limiting example, a cylindrical lead can carry electrodes be arranged about around a periphery of the lead (e.g., around a circumference of the cylindrical lead). By way of further non-limiting example, the lead can be dual-sided with one or more electrodes positioned on each side of the lead. In variations, the electrodes can be introduced on opposing sides of the patient’s spinal cord. The paddle(s) and / or the electrode(s) may generally be of any suitable number, size, and / or shape as desired to suit a particular application. By way of non-limiting example, the paddle(s) and / or the electrode(s) may span an entire length of all pain-generating DREZs in a patient (e.g., all DREZs exhibiting measurable neuroelectrical hyperactivity), as represented by break lines in FIG. 3D.

[0076] By way of non-limiting example, the methods described herein can generally be performed using one, two, three, four, five, or six or more electrodes leads, each of which can include any number and / or pattern of electrodes as desired to suit a particular application. In variations in which multiple electrodes and / or multiple leads are employed, electrical stimulation can be delivered by all or a subset of the electrodes and / or leads.

[0077] In variations, a chosen electrode can be selected so as to be positioned over one or more pain-generating DREZs as described herein. By way of non-limiting example, the electrode can have a length corresponding to an entire length of the one or more paingenerating DREZs (including, in variations, all pain-generating DREZs), such that the electrode spans the entire length of the one or more pain-generating DREZs (including, in variations, all pain-generating DREZs). By way of further non-limiting example, the electrode can span an entire area of hyperactivity in the patient’s DREZs. In variations, the electrode can have a length of at least 6 cm. In variations, the electrode can have a length of at least 7 cm. In variations, the electrode can have a length of at least 8 cm. In variations, the electrode can have a length of at least 9 cm. In variations, the electrode can have a length of at least 10 cm. In variations, the electrode can have a length of more than 10 cm.

[0078] In variations, a chosen electrode can be selected so as to be positioned over one or more DREZ regions of the patient’s spinal cord as described herein. For example, theelectrode(s) can be configured to span a width of from about 10 to about 25 mm to ensure the electrode(s) span an entire width of the DREZ regions of interest of the patient’s spinal cord.

[0079] By way of non-limiting example, if a patient perceives pain in a lower extremity (i.e. , the legs and / or feet), such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T11 to L1 DREZ regions of the patient’s spinal cord, and the electrode can have a length of at least 3.5 cm, including up to about 7 cm to ensure the electrode(s) span the entirety of the DREZs of at least the T11 to L1 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3G, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of at least the T11 to L1 DREZ regions of the patient’s spinal cord 318 (i.e., approximately the T9 to T11 vertebrae). As described herein, in some variations, it may be particularly advantageous to employ electrode(s) spanning not only the entire length of the DREZs corresponding to the novel or non-classical somatotopic map but also the spinal cord regions according to the classical map. In such variations, for example, if a patient perceives pain in a lower extremity (i.e., the legs and / or feet), such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T11 to L1 DREZ regions of the patient’s spinal cord, and such perceived pain location can further be mapped according to the classical map (refer to FIG. 2C) to the L1 to S1 DREZ regions of the patient’s spinal cord (i.e., approximately the T11 to L1 vertebrae), and the electrode(s) (e.g., second electrode) can have a length of at least 7 cm, including up to about 10 cm, to ensure the electrode(s) span the entirety of the mapped regions according to both the novel or non-classical somatotopic map and the classical map. As may be appreciated, because the mapped regions according to the novel or non-classical somatotopic map and the mapped regions according to the classical map are contiguous, an electrode having a length of at least 11 cm, including up to about 14 cm, can be employed for this purpose, such as to span the entire length of the T11 to S5 DREZs (i.e., approximately the T9 to L1 vertebrae).

[0080] By way of further non-limiting example, if a patient perceives pain in the rectal, gluteal, and / or genitalia regions, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T8 to T10 DREZ regions of the patient’s spinal cord, and the electrode can have a length of at least 3.5 cm, including up to about 7 cm, to ensure the electrode(s) span the entirety of the DREZs of at least the T8 to T10 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3H, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of at least the T8 to T19 regions of the patient’s spinal cord 318 (i.e., approximately the T6 to T8 vertebrae). As described herein, in somevariations, it may be particularly advantageous to employ electrode(s) spanning not only the entire length of the DREZs corresponding to the novel or non-classical somatotopic map but also the spinal cord regions according to the classical map. In such variations, for example, if a patient perceives pain in the rectal, gluteal, and / or genitalia regions, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T8 to T10 DREZ regions of the patient’s spinal cord, and such perceived pain location can further be mapped according to the classical map (refer to FIG. 2C) to the S2 to S5 DREZ regions of the patient’s spinal cord (i.e., approximately the L1 vertebrae), and the electrode(s) (e.g., second electrode) can have a length of at least 1 cm, including up to about 3 cm, to ensure the electrode(s) span the entirety of the mapped regions according to both the novel or non-classical somatotopic map and the classical map. As may be appreciated, because the mapped regions according to the novel or non-classical somatotopic map and the mapped regions according to the classical map are non-contiguous, first and second electrodes spaced apart from another can be employed for this purpose.

[0081] By way of yet further non-limiting example, if a patient perceives pain in the trunk, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T3 to T7 DREZ regions of the patient’s spinal cord, and the electrode can have a length of at least 7 cm, including up to about 10 cm, to ensure the electrode(s) span the entirety of the DREZs of at least the T3 to T7 regions of the patient’s spinal cord, to treat the patient’s neuropathic pain, such as is shown in FIG. 3I, which illustrates dual spinal cord leads 317A, 317B arranged to span the entirety of at least the T3 to T7 DREZ regions of the patient’s spinal cord 318 (i.e., approximately the T1 to T5 vertebrae). As described herein, in some variations, it may be particularly advantageous to employ electrode(s) spanning not only the entire length of the DREZs corresponding to the novel or non-classical somatotopic map but also the spinal cord regions according to the classical map. In such variations, for example, if a patient perceives pain in the trunk, such perceived pain location can be mapped according to the novel or non-classical somatotopic map (refer to FIG. 2B) to at least as cephalad as the T3 to T7 DREZ regions of the patient’s spinal cord, and such perceived pain location can further be mapped according to the classical map (refer to FIG. 2C) to the T2 to T12 DREZ regions of the patient’s spinal cord (i.e., approximately the C7 to T11 vertebrae), and the electrode(s) (e.g., second electrode) can have a length of at least 20 cm, including up to about 23 cm, to ensure the electrode(s) span the entirety of the mapped regions according to both the novel or non-classical somatotopic map and the classical map. As may be appreciated, because the mapped regions according to the novel or non-classical somatotopic map are encompassed by the mapped regions according to the classical map, an electrode having alength of at least 20 cm, including up to about 23 cm can be employed for this purpose.

[0082] As will be appreciated, the mapped regions of the spinal cord according to the novel or non-classical somatotopic map correspond to the spinal cord segments containing those specific DREZ levels, which do not correspond positionally with the vertebra assigned the same level. For example, the T11 sensory rootlets enter the foramen (opening) of the spine at the T11 vertebral level but travel upwardly (cephalad) toward the head a few centimeters before piercing the spinal cord surface and synapsing in the posterior grey matter over approximately a distance of 1 centimeter, along spinal cord situated at the T9 vertebra.

[0083] As will be appreciated, the patient may perceive pain in multiple regions (e.g., in the legs and the trunk), and the electrode(s) can be configured to span the entirety of the mapped regions (e.g., according to the novel or non-classical somatotopic map and, in some variations, additionally according to the classical map), such as by employing electrodes of sufficient length and / or width and / or employing a sufficient number of electrodes to span the entirety of the mapped regions, as described herein. For example, if a patient perceives pain in a lower extremity (i.e., the legs and / or feet) and the rectal, gluteal, and / or genitalia regions, an electrode having a length of at least 11 cm, including up to about 14 cm, can be employed to additionally span the T10 DREZ.

[0084] Having described several variations, it will be recognized by those skilled in the art that various modifications, alternative constructions, and equivalents can be used without departing from the spirit of the disclosure. Additionally, a number of well-known processes and elements have not been described in order to avoid unnecessarily obscuring the disclosure. Accordingly, the above description should not be taken as limiting the scope of the disclosure.

[0085] Those skilled in the art will appreciate that the presently disclosed variations teach by way of example and not by limitation. Therefore, the matter contained in the above description or shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense. The following claims are intended to cover all generic and specific features described herein, as well as all statements of the scope of the method and system, which, as a matter of language, might be said to fall therebetween.

[0086] This disclosure contains numerous citations to publications and patents. Each is hereby incorporated by reference herein for all purposes.

Claims

What is claimed is:1 . A method for treating neuropathic pain in a patient, the method comprising: arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain in the patient according to a non-classical somatotopic map; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

2. The method of claim 1 , wherein arranging the electrode comprises identifying a first location of perceived pain in the patient, mapping the first location of perceived pain to a first mapped region of the spinal cord according to the non-classical somatotopic map, and arranging the electrode in the first mapped region.

3. The method of claim 2, further comprising arranging a second electrode on the dura covering spinal cord tissue in a region of the spinal cord associated with a location of perceived pain according to a classical map.

4. The method of claim 3, wherein arranging the second electrode includes identifying a second location of perceived pain in the patient, mapping the second location of perceived pain to a second mapped region of the spinal cord according to the classical map, and arranging the electrode in the second mapped region, wherein the second mapped region is different from the first mapped region.

5. The method of any one preceding claim, wherein the perceived pain is selected from the group consisting of pain and pressure.

6. The method of any one preceding claim, further comprising testing the location of perceived pain on the patient before the step of arranging the electrode.

7. The method of claim 6, wherein the step of testing the location of perceived pain on the patient comprises stimulating the location of perceived pain.

8. The method of any one preceding claim, wherein the electrode spans an entire length of the region of the patient’s spinal cord corresponding to the location of perceived pain in the patient according to the non-classical somatotopic map.

9. The method of any one preceding claim, wherein the electrode spans an entire length of all pain-generating DREZs in the patient according to the non-classical somatotopic map.

10. The method of any one preceding claim, wherein: the perceived pain is in the trunk of the patient and the non-classical somatotopic map indicates that a pain-generating DREZ is from T3 to T7; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the non-classical somatotopic map indicates that a pain-generating DREZ is from T8 to T10; or the perceived pain is in the legs and / or feet of the patient and the non-classical somatotopic map indicates that a pain-generating DREZ is from T11 to L1 .

11. The method of claim 10, wherein: the perceived pain is in the trunk of the patient and the electrode spans at least a portion of the pain-generating DREZs from T3 to T7; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode spans at least a portion of the pain-generating DREZs from T8 to T10; or the perceived pain is in the legs and / or feet of the patient and the electrode spans at least a portion of the pain-generating DREZs from T11 to L1 .

12. The method of claim 11 , wherein: the perceived pain is in the trunk of the patient and the electrode spans an entire length of all pain-generating DREZs from T3 to T7; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode spans an entire length of all pain-generating DREZs from T8 to T10; or the perceived pain is in the legs and / or feet of the patient and the electrode spans an entire length of all pain-generating DREZs from T11 to L1 .

13. The method of any one of claims 10-13, wherein: the perceived pain is in the trunk of the patient and the electrode has a length of at least 7 cm; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode has a length of at least 3.5 cm; or the perceived pain is in the legs and / or feet of the patient and the electrode has a length of at least 3.5 cm.

14. The method of any one of claims 8-13, further comprising arranging a second electrode on the dura covering spinal cord tissue in a region of the spinal cord associated with the location of perceived pain according to a classical map.

15. The method of claim 14, wherein the second electrode spans an entire length of the region of the patient’s spinal cord corresponding to the location of perceived pain in the patient according to the classical map.

16. The method of claim 14 or 15, wherein the second electrode spans an entire length of all pain-generating DREZs in the patient according to the non-classical somatotopic map.

17. The method of any one of claims 14-16, wherein: the perceived pain is in the trunk of the patient and the classical map indicates that a pain-generating DREZ is from T2 to T12; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the classical map indicates that a pain-generating DREZ is from S2 to S5; or the perceived pain is in the legs and / or feet of the patient and the classical map indicates that a pain-generating DREZ is from L1 to S1 .

18. The method of claim 17, wherein: the perceived pain is in the trunk of the patient and the electrode spans at least a portion of the pain-generating DREZs from T2 to T12; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode spans at least a portion of the pain-generating DREZs from S2 to S5; or the perceived pain is in the legs and / or feet of the patient and the electrode spans at least a portion of the pain-generating DREZs from L1 to S1.

19. The method of claim 18, wherein: the perceived pain is in the trunk of the patient and the electrode spans an entire length of all pain-generating DREZs from T2 to T12; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode spans an entire length of all pain-generating DREZs from S2 to S5; or the perceived pain is in the legs and / or feet of the patient and the electrode spans an entire length of all pain-generating DREZs from L1 to S1 .

20. The method of any one of claims 17-19, wherein:the perceived pain is in the trunk of the patient and the electrode has a length of at least 20 cm; the perceived pain is in the rectal, gluteal, and / or genitalia regions of the patient and the electrode has a length of at least 1 cm; or the perceived pain is in the legs and / or feet of the patient and the electrode has a length of at least 7 cm.21 . A method for treating neuropathic pain in a patient, the method comprising: identifying one or more pain-generating DREZs in the patient based on measurable neuronal or neuroelectrical hyperactivity in the patient’s DREZs; arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to the identified one or more pain-generating DREZs; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

22. The method of claim 21 , further comprising: measuring neuronal or neuroelectrical hyperactivity in the patient’s DREZs before the step of arranging the electrode.

23. The method of claim 22, further comprising modifying the one or more paingenerating DREZs.

24. A method for treating neuropathic pain in a patient, the method comprising: measuring neuronal or neuroelectrical hyperactivity in the patient’s DREZs by performing a non-surgical or non-invasive technique to identify one or more pain-generating DREZs in the patient based on measurable neuronal or neuroelectrical hyperactivity in the patient’s DREZs; arranging an electrode on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to the identified one or more pain-generating DREZs; and applying an electric signal to the electrode to treat the neuropathic pain in the patient.

25. The method of claim 24, wherein the non-surgical or non-invasive technique is selected from the group consisting of remote spectral sensing, functional magnetic resonance imaging (fMRI), a positron emission tomography (PET) scan, current perception threshold testing, and magnetoencephalography (MEG).

26. The method of any one of claims 21 to 25, wherein the electrode spans an entire length of the one or more pain-generating DREZs as identified according to a non-classical somatotopic map.

27. The method of any one preceding claim, wherein the neuropathic pain is selected from the group consisting of physical pain, burning, searing, sharp, electrical, stabbing, pins- and-needles, frostbite, tearing, ripping, heat, and cold.

28. The method of any one preceding claim, wherein the patient is a spinal cord injured patient.

29. The method of claim 28, wherein the neuropathic pain is generated by spinal cord tissue caudal to a level of a spinal cord injury and the electrode is arranged below the level of the spinal cord injury.

30. The method of claim 28 or 29, wherein the neuropathic pain is perceived by the patient to be below a neurological level of the spinal cord injury and the electrode is arranged below a level of the spinal cord injury.31 . The method of any one preceding claim, wherein the electrode has a length of at least 6 cm.

32. The method of any one preceding claim, further comprising administering a neuropathic pain drug to the patient.

33. A device for treating neuropathic pain in a patient, the device comprising: an electrode configured to be arranged on the dura covering spinal cord tissue in a region of the patient’s spinal cord corresponding to a location of perceived pain according to a non-classical somatotopic map; and a stimulation generator configured to deliver an electric signal to the electrode to treat neuropathic pain in the patient.

34. The device of claim 33, wherein the electrode has a width of from about 10 to about 25 mm.

35. The device of claim 33 or 34, wherein the electrode has a length of from at least 6 cm.

36. The device of any one of claims 33-35, wherein the electrode comprises a plurality of electrodes.

37. The device of claim 36, wherein the plurality of electrodes form an electrode array.

38. The device of claim 36 or 37, wherein the plurality of electrodes are formed on a cylindrical lead.

39. The device of claim 36 or 37, wherein the plurality of electrodes are formed on a paddle.

40. The device of any one of claims 33-39, wherein the electrode comprises a plurality of electrode leads.

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