Low-dose mesenchymal stem cell therapy for discogenic pain: safety and efficacy results from a 1-year feasibility study.

Aim: To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP). Methods: Nine participants with chronic LBP originating from single-level lumbar disc disease underwent intradiscal injection of 10 million ADMSCs with optional repetition after 6 months. Results: No unexpected or serious adverse events were recorded. Seven (78%) of participants reported reductions in pain 12 months after treatment. Five (56%) reported increased work capacity. Three (33%) reduced analgesic medication. Improvements in EQ-5D and Oswestry disability index results were observed. MRI demonstrated no further disc degeneration and improvements to annular fissures and disc protrusions. Conclusion: This study provides initial evidence of safety and efficacy of ADMSCs for discogenic LBP.

Retrospective Analysis of Real-World Outcomes of 10 kHz SCS in Patients with Upper Limb and Neck Pain.

BACKGROUND: Patients living with chronic upper limb and neck (ULN) pain are reliant on often ineffective therapies as they face limited options for effective long-term treatment. OBJECTIVE: Prospective clinical studies have demonstrated that high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS) is effective in treating chronic pain in multiple etiologies including ULN pain. This study aimed at validating the findings from clinical studies on ULN in a real-world cohort. STUDY DESIGN: A retrospective, observational review. SETTING: A multicenter review between April 2016 and August 2019. PATIENTS AND METHODS: Anonymized data were extracted from a real-world database of 47 consecutive patients aged ≥18 years of age with chronic upper limb and/or neck pain who were trialed and permanently implanted with 10 kHz SCS. Patient-reported pain relief, quality of life, function, sleep and medication use were extracted from anonymised patient records where available. Responder rates, defined as the proportion of patients with at least 50% pain relief at the end of trial and the last visit after implantation, were calculated. RESULTS: All patients reported successful response (≥50% pain relief) at the end of trial and >75% patients continued to respond to the therapy at the last follow-up period. Majority (72%) of patients reported improvement in function, about half of the patients (53%) reported improvement in sleep and one-third of the patients (36%) reported reducing their medication at last follow-up. CONCLUSION: 10 kHz SCS provides durable pain relief to patients with chronic upper limb and neck pain.

10 kHz spinal cord stimulation for chronic upper limb and neck pain: Australian experience.

PURPOSE: Intractable upper limb and neck pain has traditionally been a challenging pain condition to treat, with conventional spinal cord stimulation (SCS) often inducing positional variation in paraesthesia and/or inadequate coverage of axial neck pain. The purpose of this Australian multi-centre prospective, clinical trial was to assess the safety and effectiveness of paraesthesia-independent 10 kHz SCS for the treatment of upper limb and neck pain. METHODS: Subjects with chronic, intractable neck and/or upper limb pain of ≥ 5 cm (on a 0-10-cm visual analogue scale) were enrolled (ACTRN12614000153617) following human research ethics committee approval. Subjects were implanted with two epidural leads spanning C2-C6 vertebral bodies. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp., Redwood City, CA, USA) and included in the safety and effectiveness evaluation at 3 months post-implant (primary endpoint assessment, PEA) and followed to 12 months. RESULTS: Overall, 31/38 (82.6%) subjects reported a successful 10 kHz SCS trial and proceeded to a permanent implant. Twenty-three of 30 subjects (76.7%) met the PEA. Subjects reported a reduction in neck pain and upper limb pain from baseline at the PEA (8.1 ± 0.2 cm vs. 2.9 ± 0.5 cm, 7.3 ± 0.3 cm vs. 2.5 ± 0.5 cm, respectively, p ≤ 0.0001). Disability, as measured by pain disability index score, decreased from 42.6 ± 2.6 at baseline to 22.7 ± 3.2 at PEA. Results were maintained 12 months post-implant. No neurological deficits, nor reports of paraesthesia, were observed. CONCLUSIONS: Stable, long-term results demonstrated that 10 kHz SCS is a promising therapy option for intractable chronic upper limb and neck pain.

A review of spinal cord stimulation systems for chronic pain.

Spinal cord stimulation (SCS) applications and technologies are fast advancing. New SCS technologies are being used increasingly in the clinical environment, but often there is a lag period between the clinical application and the publishing of high-quality evidence on safety and efficacy. Recent developments will undoubtedly expand the applicability of SCS, allowing more effective and individualized treatment for patients, and may have the potential to salvage patients who have previously failed neuromodulation. Already, high-level evidence exists for the safety, efficacy, and cost-effectiveness (Level I-II) of traditional SCS therapies in the treatment of chronic refractory low back with predominant limb pain (regardless of surgical history). More than half of all patients with chronic painful conditions experience sustained and significant levels of pain reduction following SCS treatment. Although only limited evidence exists for burst stimulation, there is now Level I evidence for both dorsal root ganglion SCS and high-frequency SCS that demonstrates compelling results compared with traditional therapies. The body of evidence built on traditional SCS research may be redundant, with newer iterations of SCS therapies such as dorsal root ganglion SCS, high-frequency SCS, and burst SCS. A number of variables have been identified that can affect SCS efficacy: implanter experience, appropriate patient selection, etiologies of patient pain, existence of comorbidities, including psychiatric illness, smoking status, and delay to SCS implant following pain onset. Overall, scientific literature demonstrates SCS to be a safe, effective, and drug-free treatment option for many chronic pain etiologies.

Peripheral Nerve Field Stimulation Therapy for Patients With Thoracic Pain: A Prospective Study.

OBJECTIVE: Relative to the number of patients suffering chronic lumbar and cervical pain, fewer patients suffer persistent thoracic pain. Consequently there is less literature, with smaller sample sizes, reporting treatment of this cohort. Here, we assess peripheral nerve field stimulation (PNfS) as a potential treatment for chronic thoracic pain. MATERIALS AND METHODS: This study included 20 consecutive chronic thoracic pain sufferers that responded successfully to PNfS trial. The patients were subsequently implanted with permanent eight-contact electrode linear percutaneous leads within their major area of pain. Patients were followed up at 12 months for outcome reporting. All 20 patients were considered in the statistical analysis, despite removal of three devices prior to follow up. RESULTS: The average baseline pre-treatment Numerical Pain Rating Scale (NPRS) score was 7.75 ± 1.4. Following PNfS, the mean NPRS score was 2.25 ±2.14, reflecting a significant average improvement of 5.5 ± 3.31. Three patients were explanted prior to follow up: the first gained excellent thoracic pain relief but pain at the Implantable Pulse Generator (IPG) site could not be overcome, the second achieved excellent pain relief but the PNfS was removed due to recurrent infection and in the final instance, the intervention offered only poor relief and the device removed. CONCLUSION: PNfS is an effective intervention for intractable disabling thoracic pain, offering sustained and worthwhile pain relief, for the overwhelming majority of the cohort. This may be especially true when considering a combined treatment approach of PNfS and analgesic use to manage remnant pain.

Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review.

Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition.

High Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Chronic Pain: 6-Month Australian Clinical Experience.

BACKGROUND: High frequency spinal cord stimulation at 10 kHz (HF10 therapy) represents a prominent advance in spinal cord stimulation (SCS) therapy, having demonstrated enhanced efficacy in patients with back and leg pain and pain relief without paresthesia that is sustained at 24 months post implant. OBJECTIVE: To report on the effectiveness HF10 SCS therapy for a wide range of intractable pain conditions in clinical practice. STUDY DESIGN: Retrospective investigation of 256 patients who trialed HF10 SCS for chronic intractable pain of various etiologies. SETTING: Three Australian pain clinics. METHODS: Two hundred fifty-six patients trialed HF10 SCS with view of a permanent implant if successful. Pain distributions included back + leg, back only, head ± neck, and neck ± arm/shoulder. About 30% of patients had previously failed traditional low-frequency paresthesia-based stimulation, while the remaining cohort were either highly refractory to treatment or not recommended by the pain physician for traditional SCS. Pain scores (numerical pain rating scale - NPRS) and functional outcome measures (Oswestry Disability Index - ODI; and activity tolerance times) were assessed at baseline, post-trial, and at 3 and 6 months post-implant as available in the medical records. RESULTS: Of the 256 patients, 189 (73%) reported a positive trial and were implanted. Patients with back + leg pain demonstrated the highest trial success rate (81%). A mean reduction in pain, among those for whom data were available, of 50% was sustained up to 6 months post-implant across the entire patient population. Sixty-eight percent of patients who failed traditional SCS reported a positive trial and mean pain relief at 6 months was 49% (P < 0.001). An 8.6 point reduction in ODI (21%) at 6 months and improved sitting, standing, and walking tolerances were also reported. LIMITATIONS: As data was collected retrospectively, missing data points were unavoidable; this was primarily due to inconsistent data collection and patients being lost to follow-up. Patient populations were diverse and a control group was not appropriate in this setting. CONCLUSIONS: These retrospective results demonstrate a significant advancement for patients suffering with chronic intractable pain and are consistent with recently published clinical results for HF10 SCS. HF10 SCS appears to be a viable, paresthesia-free alternative to traditional SCS, with high trial success rates, demonstrated effectiveness in a range of pain distributions including those typically difficult to treat with traditional SCS, and the possibility to restore pain control in patients who have previously failed traditional SCS. KEY WORDS: Spinal cord stimulation, high frequency stimulation, HF10, paresthesia-free stimulation, back pain, leg pain, cervical pain, neuromodulation.

Prevalence and Characteristics of Discogenic Pain in Tertiary Practice: 223 Consecutive Cases Utilizing Lumbar Discography.

BACKGROUND: Between 26% and 42% of chronic low back pain is attributed to internal disc disruption of lumbar intervertebral discs. These prevalence estimates and data characterizing discogenic pain originate largely from research at elite practices, conducted 20 years ago. With few studies since, their concordance with rates in community practice has rarely been addressed. OBJECTIVE: To assess the prevalence and key features of discogenic pain within community-based tertiary practice, and to evaluate the accuracy and clinical utility of discography. DESIGN: This prospective, three-year study of 223 consecutive cases of chronic low back pain used image-guided lumbar discography to identify symptomatic and flanking asymptomatic discs. A subset of patients (n = 195) had previously undergone posterior column blocks to investigate spinal facet and/or sacroiliac joints as contributing pain sources. RESULTS: A total of 644 discs were tested without infection or complication. Positive discograms were recorded in 74% of patients, with 22.9% negative and 3.1% assessed as indeterminate. Among patients receiving both discography and diagnostic blocks, 63% had proven discogenic pain, 18% had pain of mixed etiology and 14% remained undiagnosed. Taking into account all low back pain cases during this study (n = 756), discogenic pain prevalence was 21.8% (95% CI: 17-26%). CONCLUSION: The prevalence of discogenic pain in this community practice is below the range, but within confidence intervals, previously reported. Prevalence is considerably elevated, however, among well-selected patients and discography enabled a firm diagnosis in most such cases. These findings are broadly in keeping with those reached in key publications and support the clinical utility of discography.

Peripheral nerve field stimulation for chronic headache: 60 cases and long-term follow-up.

OBJECTIVE: The objective of this study is to evaluate the efficacy of peripheral nerve field stimulation (PNFS) for the treatment of chronic headache conditions. MATERIALS AND METHODS: For more than a four-year period, 83 patients underwent a trial of a PNFS system targeting the nerve regions including occipital and supraorbital and infraorbital nerves, which best corresponded with their area of head pain. Sixty patients reported a successful trial and underwent a subsequent implant of the PNFS system. Questionnaires, along with patients' charts, were used to assess outcomes as follows: pain (11-point numerical pain rating scale), analgesic use, depression (Zung Depression Scale), disability (Neck Disability Index), patient satisfaction, and surgical complications. Patients were followed up for an average of 12.9 ± 9.4 months (range 3-42 months). RESULTS: An average pain reduction of 4.8 ± 2.3 pain scale points was observed (preimplant 7.4 ± 1.6; follow-up 2.6 ± 2.1 [p ≤ 0.001]). Of the 60 patients implanted, 41 reported >50% pain relief. Medication use was reduced in 83% of patients who were previously taking analgesics or prophylactic medications. Similarly, reductions in degree of disability and depression also were observed. Of the 60 cases, ten surgical revisions were required; however, no long-term complications were reported. CONCLUSIONS: PNFS for chronic headache is an evolving therapy. This study demonstrates that this reversible and effective treatment can be a promising pain relief strategy for this often intractable condition.

To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis.

OBJECTIVE: To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis. DESIGN: We present a case report of osteoarthritis of the knee treated with photo-activated platelet-rich plasma injections (PAPRP). METHODS: After utilising conventional osteoarthritis treatment methods a patient underwent a course of PAPRP injections. The patient outcome was measured using the numerical pain rating scale (NPRS) and the Western Ontario and McMaster Universities Arthritis (WOMAC) Index. RESULTS: Following treatment the patient reported improvements in both pain and function as measured by the NPRS and WOMAC Index, respectively. The patient was followed up for 18 weeks, at which time no significant complications were noted. CONCLUSIONS: In this case report of osteoarthritis, with strict control of conventional therapy variables, PAPRP injections demonstrated improvement in all recorded outcome measures. The results of this case report highlight the need to further investigate the use of PAPRP in the treatment of symptomatic knee osteoarthritis.

Photoactivated platelet-rich plasma therapy for a traumatic knee chondral lesion.

To evaluate the effect of combining photoactivation therapy with platelet-rich plasma injections in the treatment of a traumatic chondral lesion of the knee. A 38-year-old man presented with left-knee pain and swelling following a basketball injury. MRI demonstrated a full-thickness lateral tibial plateau chondral flap with subchondral cyst formation and marrow oedema. The patient underwent a course of photoactivated platelet-rich plasma (PAPRP) injections. Patient outcome measures included the numerical pain rating scale and the Western Ontario and McMaster Universities Arthritis Index 3.0 (WOMAC). Following treatment, the patient reported improvement in both pain and function as measured by the numerical pain-rating scale and WOMAC. MRI showed resolution of subchondral bone marrow bruising/oedema. No complications were noted. In this case report, PAPRP injections demonstrated improvement in all recorded outcome measures. Recognising the limitations of a single case report, the results highlight the need for more formal controlled trials to determine the potential use of PAPRP in the treatment of chondral lesions.

Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature.

OBJECTIVE: To evaluate the clinical outcomes of 100 consecutive patients receiving peripheral nerve field stimulation (PNFS) for the treatment of chronic intractable pain. DESIGN: Prospective, observational study. SETTING: A private interventional pain specialty referral practice. PATIENTS: One hundred consecutive private practice patients receiving PNFS for the treatment of chronic craniofacial, thorax, lumbosacral, abdominal, pelvic, and groin pain conditions. OUTCOME MEASURES: Pain (11-point numerical rating scale), complications, changes to analgesic use and employment status, disability (Oswestry or Neck Disability Indexes), depression (Zung Depression Index), and patient satisfaction. RESULTS: We demonstrate an average pain reduction of 4.2 ± 2.5 pain scale points on an 11-point scale following PNFS (preimplant pain score of 7.4 ± 1.7 to a follow-up average of 3.2 ± 2.3 pain scale points) (P≤0.00). At a follow-up period of 8.1 ± 4.7 months (range 1-23 months), an overall 72% of patients reduced their analgesic use following PNFS. Patients receiving a lumbosacral PNFS for chronic low back pain reported a significant reduction in disability following treatment, as determined by the Oswestry Disability Index. Of the 100 cases, no long-term complications were reported. CONCLUSIONS: This prospective 100 consecutive PNFS patient outcome study demonstrates that PNFS can be a safe and effective treatment option for, otherwise, intractable chronic pain conditions. PNFS has the potential to fundamentally change the way we think about pain management.

The prospect of stem cells as multi-faceted purveyors of immune modulation, repair and regeneration in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is characterised by an autoimmune attack on components of the myelin sheath and axons leading to neurological disability. Although long-approved current treatments for MS have so far only targeted immune components of the disease in a non-specific manner, the efficacy of these immunomodulatory treatments are limited given that they are only immunosuppressive and/ or immunoregulatory and do not prevent long-term disease progression. As such, there is a clear need for more effective therapies that are capable of targeting other aspects of the disease including neurodegeneration, demyelination and the underlying causes of the autoimmune state. Emerging data suggest that hematopoietic, mesenchymal and neural stem cells have the promise to restore self-tolerance, to provide in situ immunomodulation and neuroprotection as well as to promote regeneration. This review will summarise burgeoning experimental and clinical evidence supporting the application of these stem cell populations for the treatment of MS.

Penetration of a cervical radicular artery during a transforaminal epidural injection.

BACKGROUND: Inadvertent cannulation or penetration of the cervical radicular arteries during cervical transformaminal epidural injections (TFESIs) is a serious clinical risk, and purportedly, the cause of possible spinal cord injury sustained during this procedure. CASE: Here, we present a case of inadvertent intravascular penetration of a cervical radicular artery during a C5-6 TFESI and demonstrate the best image capture to date of direct ramification of a cervical radicular artery into the anterior spinal artery. CONCLUSION: This observation reinforces the need for contrast injection and real-time digital subtraction fluoroscopy during cervical TFESIs for the prevention of spinal cord injury and fatalities.

Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis.

Bone marrow transplantation (BMT) potentially represents a novel therapy for the amelioration and even cure for multiple sclerosis (MS). It has important advantages over immunosuppressive drug treatments because, while effecting broad-based ablation of the immune system and autoreactive cells, it provides an important means for overcoming the resultant immunodeficiency, while possibly restoring self-tolerance. However, both of these benefits are predicated on a functional thymus that undergoes profound age-induced atrophy from puberty. Reversal of thymic atrophy has been achieved by several procedures, including removal of sex steroids by surgical or chemical (LHRH agonist) castration. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we combined BMT with androgen depletion to induce immune regeneration, and investigated the kinetics of increased thymic function on immune reconstitution and disease reduction. We show that androgen depletion significantly increased the efficacy of BMT to ameliorate the clinical signs of EAE while concurrently restoring the periphery with increased naive and regulatory lymphocytic populations. Upon rechallenge, mice with a regenerated thymus had a slower onset of clinical symptoms compared with mice undergoing BMT only. These results suggest that thymic regeneration strategies may be used as a complement to conventional BMT protocols for the treatment of MS.

Impact of the neuroendocrine system on thymus and bone marrow function.

The nervous, endocrine, and immune systems interact to adapt to infection, inflammation, and tissue injury. Neural control is mediated in several ways, one of them being through the neuroendocrine regulation of the secretion of hypothalamic and pituitary hormones. The hormonal effects on the immune system range from the impact of steroidal hormones, which exhibit inhibitory effects over immune functions, to growth hormone, prolactin and neurohypophyseal hormones, known to stimulate and modulate humoral and cellular aspects of the immune system. This review will discuss the mechanisms behind the immunomodulatory role of the neuroendocrine system, including the critically important feedback loops required to maintain balance for these bidirectional interactions and alterations that occur with age.