Dorsal root ganglion stimulation (DRG-S) is a form of selective neuromodulation therapy that targets the dorsal root ganglion. DRG-S offers analgesia in a variety of chronic pain conditions and is approved for treatment of complex regional pain syndrome (CRPS) by the US Food and Drug Administration (FDA). There has been increasing utilization of DRG-S to treat various neuropathic pain syndromes of the lower extremity, although evidence remains limited to one randomized controlled trial and 39 observational studies. In this review, we appraised the current evidence for DRG-S in the treatment of lower extremity neuropathic pain using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The primary outcome was change in pain intensity after DRG-S compared to baseline. We stratified presentation of results based of type of neuropathy (CRPS, painful diabetic neuropathy, mononeuropathy, polyneuropathy) as well as location of neuropathy (hip, knee, foot). Future powered randomized controlled trials with homogeneous participants are warranted.

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IntroductionHabituation and loss of efficacy from spinal cord stimulation are commonly reported. This retrospective analysis investigated rescue of analgesia from spinal cord stimulation failure after implementing a strategy called a stimulation holiday, during which spinal cord stimulation is interrupted for a defined period and subsequently restarted.MethodsA 6-year review (June 1, 2016–May 13, 2022) from a tertiary care center was conducted on patients who underwent 10 kHz frequency dorsal column spinal cord stimulation for ≥3 months, experienced loss of efficacy (≤30% pain relief or patient self-report of lack of meaningful pain relief), subsequently underwent a stimulation holiday, and then restarted spinal cord stimulation. The primary outcome was comparison of pain relief and responder rate (≥50% relief in pain intensity) before and after stimulation holiday.ResultsOf 212 patients, 40 (18.9%) experienced loss of efficacy at a mean follow-up period of 452.7±326.4 days after stimulator implantation and underwent stimulation holiday. Pain relief was significantly higher 1 month after stimulation holiday (39.4%±28.6%) compared with before stimulation holiday (8.7%±13.0%; mean difference 30.6%, 95% CI 21.9% to 39.3%, paired t-test p<0.001). A significantly higher responder rate (≥50% relief in pain intensity) was identified after stimulation holiday (57.5%) compared with before stimulation holiday (0%; Fisher’s exact test p<0.001). Associations of superior pain relief and responder rate remained significant at 3 and 6 months after stimulation holiday.DiscussionPatients who experience loss of efficacy from spinal cord stimulation habituation could attempt a stimulation holiday rather than abandon therapy. Rescue of analgesia may be achieved after implementing a stimulation holiday and restarting spinal cord stimulation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

Pain originating from the intervertebral disc (discogenic pain) is a prevalent manifestation of low back pain and is often challenging to treat. Of recent interest, regenerative medicine options with injectable biologics have been trialed in discogenic pain and a wide variety of other painful musculoskeletal conditions. In particular, the role of bone marrow aspirate concentrate (BMAC) and culture-expanded bone marrow derived mesenchymal stromal cells (BM-MSCs) in treating discogenic pain remains unclear. The primary objective of this systematic review was to appraise the evidence of intradiscal injection with BMAC and culture-expanded BM-MSCs in alleviating pain intensity from discogenic pain. Secondary outcomes included changes in physical function after intradiscal injection, correlation between stromal cell count and pain intensity, and anatomical changes of the disc assessed by radiographic imaging after intradiscal injection. Overall, 16 studies consisting of 607 participants were included in qualitative synthesis without pooling. Our synthesis revealed that generally intradiscal autologous or allogeneic BMAC and culture-expanded BM-MSCs improved discogenic pain compared to baseline. Intradiscal injection was also associated with improvements in physical functioning and positive anatomical changes on spine magnetic resonance imaging (improved disc height, disc water content, Pfirrmann grading) although anatomical findings were inconsistent across studies. However, the overall GRADEscore for this study was very low due to heterogeneity and poor generalizability. There were no serious adverse events reported post intradiscal injection except for a case of discitis.

This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms.

Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) or Plasma rich in growth factors (PRGF) continues to develop, however evidence appraisal for treatment of radicular pain remains lacking. Thus, we performed a systematic review to evaluate the effectiveness of epidural steroid injections containing PRP or related products to treat radicular pain. Embase, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were queried. Twelve studies were included in qualitative analysis, consisting of three randomized controlled trials and nine observational studies. The primary outcome was pain intensity, and secondary outcomes included functional improvement, anatomical changes on advanced imaging, and adverse events. All studies identified improved pain intensity and functional outcomes after epidural injection of PRP, PRGF and/or PL. Similar or longer lasting pain relief was noted in the PRP cohort compared to the cohort receiving epidural steroid injections with effects lasting up to 12–24 months. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis revealed a very-low certainty of evidence due to risk of bias, indirectness, and imprecision.