Spinal Cord Stimulation for Visceral Pain: Present Approaches and Future Strategies.

INTRODUCTION: The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges. METHODS: A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain. RESULTS: To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative. CONCLUSIONS: Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy.

Assessment of axonal recruitment using model-guided preclinical spinal cord stimulation in the ex vivo adult mouse spinal cord.

Spinal cord stimulation (SCS) is used clinically to limit chronic pain, but fundamental questions remain on the identity of axonal populations recruited. We developed an ex vivo adult mouse spinal cord preparation to assess recruitment following delivery of clinically analogous stimuli determined by downscaling a finite element model of clinical SCS. Analogous electric field distributions were generated with 300-µm × 300-µm electrodes positioned 200 µm above the dorsal column (DC) with stimulation between 50 and 200 µA. We compared axonal recruitment using electrodes of comparable size and stimulus amplitudes when contacting the caudal thoracic DC and at 200 or 600 µm above. Antidromic responses recorded distally from the DC, the adjacent Lissauer tract (LT), and in dorsal roots (DRs) were found to be amplitude and site dependent. Responses in the DC included a unique component not seen in DRs, having the lowest SCS recruitment amplitude and fastest conduction velocity. At 200 µm above, mean cathodic SCS recruitment threshold for axons in DRs and LT were 2.6 and 4.4 times higher, respectively, than DC threshold. SCS recruited primary afferents in all (up to 8) caudal segments sampled. Whereas A and C fibers could be recruited at nearby segments, only A fiber recruitment and synaptically mediated dorsal root reflexes were observed in more distant (lumbar) segments. In sum, clinically analogous SCS led to multisegmental recruitment of several somatosensory-encoding axonal populations. Most striking is the possibility that the lowest threshold recruitment of a nonprimary afferent population in the DC are postsynaptic dorsal column tract cells (PSDCs) projecting to gracile nuclei.NEW & NOTEWORTHY Spinal cord stimulation (SCS) is used clinically to control pain. To identify axonal populations recruited, finite element modeling identified scaling parameters to deliver clinically analogous SCS in an ex vivo adult mouse spinal cord preparation. Results showed that SCS first recruited an axonal population in the dorsal column at a threshold severalfold lower than primary afferents. These putative postsynaptic dorsal column tract cells may represent a previously unconsidered population responsible for SCS-induced paresthesias necessary for analgesia.

Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

Functional organization and connectivity of the dorsal column nuclei complex reveals a sensorimotor integration and distribution hub.

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organized by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organization and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organization, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibers, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organization and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

Punctate Midline Myelotomy: A Historical Overview and Case Series with Detailed Efficacy and Side Effect Profiles.

OBJECTIVE: To review our experience with punctate midline myelotomy (PMM) for malignant and benign visceral pain with an emphasis on detailed side-effect profiles and efficacy. METHODS: Thirteen adults (5 men) underwent microsurgical transverse-crush PMM. RESULTS: Median follow-up for the benign pain group (n = 6) was 17.5 months (10-72) and for the malignant group (n = 7) was 8 months (0.5-31). Five of seven patients in the malignant pain group obtained excellent, lasting relief. Two had initial relief followed by worsening pain with disease progression. In the benign pain group, two patients with endodermal-origin pain (gastrointestinal tract, bladder) had complete, long-lasting relief. Three patients with mesodermal-origin pain (ureter) had excellent relief for 2-3 months, followed by recurrence in two and partial (40%) recurrence in the third. One man with pre-existing cervical myelopathy underwent PMM for benign testicular-region pain from which he had long-term relief but only transient relief of coexisting low-back and leg pain. There were no motor deficits in either group, and all patients remained ambulatory and continent. The most common side effect was transient numbness of the medial leg and foot. Two patients (both with pre-existing spinal pathology) reported persistent moderate reduction of bowel, bladder, and sexual sensation. CONCLUSIONS: PMM offers substantial pain relief for carefully selected patients with intractable visceral pain. Relief from primarily endoderm-derived structures was most complete and long-lasting. Relief from mesoderm-derived structures was typically transient or incomplete. There was essentially no relief from pain of ectoderm-derived structures. Detailed preoperative counseling is important, especially for those with pre-existing neurologic deficits.

Punctate Midline Myelotomy for Chronic, Intractable, Non-malignant Visceral Pain: A Case Report.

Punctate midline myelotomy (PMM) has a strong anatomic and functional basis for its role in the treatment of visceral pain. The procedure derived from advances in the understanding of the postsynaptic dorsal column (PSDC) pathway and the converging laboratory and clinical evidence that this spinal cord pathway plays a dominant role in conveying visceral pain to higher levels of the nervous system. The result of PMM is a concise, effective interruption of the PSDC pathway with minimal to no side effects. While considerable evidence now documents that PMM has good efficacy and safety in treating malignant visceral pain, there is little experience describing its application to chronic severe refractory visceral pain of benign origin.  We present the case of a patient with a 13-year history of severe non-malignant chronic abdominal visceral pain who obtained complete pain relief from a PMM at the T7 level. Intraoperative somatosensory evoked potential (SSEP) monitoring did not show changes after making the PMM lesion. As of six-months postoperative follow-up, the benefit shows no sign of fading, all pain medications have been discontinued, and there has been no impairment of motor function, bowel or bladder function, sexual function, gait or station. Upon detailed questioning, the patient endorsed only mild subjective reduced sensation of the inner aspects of her feet that was not bothersome to her. On detailed testing, position sense was preserved throughout; the Romberg test was negative, and the only finding was reduced vibratory sensation over the great toe pads. We cautiously suggest that the PMM operation may allow relief from severe, intractable, benign visceral pain syndromes for which effective treatments are otherwise elusive. The procedure warrants further study for such conditions.