scholarly journals Prevention and reversal of latent sensitization of dorsal horn neurons by glial blockers in a model of low back pain in male rats

2017 ◽  
Vol 118 (4) ◽  
pp. 2059-2069 ◽  
Author(s):  
Juanjuan Zhang ◽  
Siegfried Mense ◽  
Rolf-Detlef Treede ◽  
Ulrich Hoheisel
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Nerve Growth Factor ◽  
Dorsal Horn ◽  
Microglial Activation ◽  
Low Back ◽  
Astrocyte Activation ◽  
Dorsal Horn Neurons ◽  
Resting Activity ◽  
Stimulation Of

In an animal model of nonspecific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues. To block microglial activation, minocycline was continuously administered intrathecally starting 1 day before or 2 days after the first NGF injection. The glia inhibitor fluorocitrate that also blocks astrocyte activation was administrated 2 days after the first injection. Minocycline applied before the first NGF injection reduced the manifest sensitization after the second NGF injection to control values. The proportion of neurons responsive to stimulation of deep tissues was reduced from 50% to 17.7% ( P < 0.01). No significant changes occurred when minocycline was applied after the first injection. In contrast, fluorocitrate administrated after the first NGF injection reduced significantly the proportion of neurons with deep input (15.8%, P < 0.01). A block of glia activation had no significant effect on the increased resting activity. The data suggest that blocking microglial activation prevented the NGF-induced latent spinal sensitization, whereas blocking astrocyte activation reversed it. The induction of spinal neuronal sensitization in this pain model appears to depend on microglia activation, whereas its maintenance is regulated by activated astrocytes. NEW & NOTEWORTHY Activated microglia and astrocytes mediate the latent sensitization induced by nerve growth factor in dorsal horn neurons that receive input from deep tissues of the low back. These processes may contribute to nonspecific low back pain.

scholarly journals The Lumbodorsal Fascia as a Potential Source of Low Back Pain: A Narrative Review

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jan Wilke ◽  
Robert Schleip ◽  
Werner Klingler ◽  
Carla Stecco
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Dorsal Horn ◽  
Morphological Changes ◽  
Low Back ◽  
Dorsal Horn Neurons ◽  
Potential Source ◽  
Stimulation Of

The lumbodorsal fascia (LF) has been proposed to represent a possible source of idiopathic low back pain. In fact, histological studies have demonstrated the presence of nociceptive free nerve endings within the LF, which, furthermore, appear to exhibit morphological changes in patients with chronic low back pain. However, it is unclear how these characteristics relate to the aetiology of the pain. In vivo elicitation of back pain via experimental stimulation of the LF suggests that dorsal horn neurons react by increasing their excitability. Such sensitization of fascia-related dorsal horn neurons, in turn, could be related to microinjuries and/or inflammation in the LF. Despite available data point towards a significant role of the LF in low back pain, further studies are needed to better understand the involved neurophysiological dynamics.

Short-term swimming exercise attenuates the sensitization of dorsal horn neurons in rats with NGF-induced low back pain

2018 ◽  
Vol 22 (8) ◽  
pp. 1409-1418 ◽  
Author(s):  
G. de Azambuja ◽  
U. Hortscht ◽  
U. Hoheisel ◽  
M.C. Oliveira Fusaro ◽  
S. Mense ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Dorsal Horn ◽  
Swimming Exercise ◽  
Low Back ◽  
Short Term ◽  
Dorsal Horn Neurons

Efficacy of Transverse Tripolar Spinal Cord Stimulator for the Relief of Chronic Low Back Pain from Failed Back Surgery

2008 ◽  
Vol 3;11 (5;3) ◽  
pp. 333-338
Author(s):  
Asokumar Buvanendran
Keyword(s):  
Spinal Cord ◽  
Low Back Pain ◽  
Back Pain ◽  
Case Report ◽  
Pain Relief ◽  
Failed Back Surgery Syndrome ◽  
Low Back ◽  
Failed Back Surgery ◽  
Back Surgery ◽  
Stimulation Of

Background: Failed back surgery syndrome is a common clinical entity for which spinal cord stimulation has been found to be an effective mode of analgesia, but with variable success rates. Objective: To determine if focal stimulation of the dorsal columns with a transverse tripolar lead might achieve deeper penetration of the electrical stimulus into the spinal cord and therefore provide greater analgesia to the back. Design: Case report. Methods: We describe a 42-year-old female with failed back surgery syndrome that had greater back pain than leg pain. The tripolar lead configuration was achieved by placing percutaneously an octapolar lead in the spinal midline followed by 2 adjacent quadripolar leads, advanced to the T7-T10 vertebral bodies. Results: Tripolar stimulation pattern resulted in more than 70% pain relief in this patient during the screening trial, while stimulation of one or 2 electrodes only provided 20% pain relief. After implantation of a permanent tripolar electrode system with a single rechargeable battery, the pain relief was maintained for one year. Conclusion: This is case report describing a case of a patient with chronic low back pain with a diagnosis of failed back surgery syndrome in which transverse tripolar stimulation using an octapolar and 2 quadripolar leads appeared to be beneficial. The transverse tripolar system consists of a central cathode surrounded by anodes, using 3 leads. This arrangement may contribute to maximum dorsal column stimulation with minimal dorsal root stimulation and provide analgesia to the lower back. Key words: Epidural, low back pain, spinal cord stimulation, failed back surgery syndrome, tripolar stimulation

scholarly journals Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain

Pain ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2210-2220 ◽  
Author(s):  
Martin Schmelz ◽  
Patrick Mantyh ◽  
Anne-Marie Malfait ◽  
John Farrar ◽  
Tony Yaksh ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Chronic Low Back Pain ◽  
Low Back ◽  
Nerve Growth ◽  
Osteoarthritis Pain

Sensory findings after stimulation of the thoracolumbar fascia with hypertonic saline suggest its contribution to low back pain

Pain ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 222-231 ◽  
Author(s):  
Andreas Schilder ◽  
Ulrich Hoheisel ◽  
Walter Magerl ◽  
Justus Benrath ◽  
Thomas Klein ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Hypertonic Saline ◽  
Low Back ◽  
Thoracolumbar Fascia ◽  
Stimulation Of

scholarly journals Anti-Nerve Growth Factor in the Treatment of Low Back Pain and Radiculopathy: A Systematic Review and a Meta-Analysis

2014 ◽  
Vol 17;1 (1;17) ◽  
pp. E45-E60
Author(s):  
Joao E D Amadera
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pain Relief ◽  
Adverse Effects ◽  
Functional Improvement ◽  
Low Back ◽  
Exclusion Criteria ◽  
Nerve Growth

Background: Low back pain with or without radiculopathy is an important cause of disability and economic expenditure. However, many patients are not meeting optimal pain control through existing treatments. Recent studies have linked nerve growth factor (NGF) and the pathophysiology of persistent pain. Anti-NGF could be an alternative drug treatment for low back pain. Objective: Systematically review the efficacy and safety of anti-NGF in the treatment of low back pain. Methods: A systematic review of the literature with no language, date or publication status restriction, using Medline, EMBASE, Cochrane Library, and the clinicaltrials.gov database. Additional literature was retrieved by conferring with experts in the field or reviewing bibliographies and annals of meetings and congresses. Search terms included “monoclonal antibodies,” “nerve growth factor,” “anti-ngf,” “fulranumab,” “tanezumab,” “sciatica,” “back pain,” and “spine.” Study Design: Inclusion criteria were observational studies with safety as an outcome and randomized or nonrandomized controlled trials studying the efficacy and/or the safety of antiNGF drugs on low back pain. Exclusion criteria included patients with autoimmune conditions or osteoporosis. Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, and quality of evidence (GRADE approach). Results: 1,168 studies were retrieved. After excluding duplicates and applying the inclusion/ exclusion criteria, 4 RCTs remained (n = 2,109): 2 for tanezumab, one for REGN475, and one for fulranumab. Only the tanezumab studies showed any significant difference over placebo (n = 1,563) for both pain relief and functional improvement. Conclusions: There is very low evidence that systemically administered anti-NGF therapy has a small positive effect compared to placebo for both pain relief (standarized mean difference [SMD] = -0.29, 95% confidence interval [CI] -0.58 to 0.00) and functional improvement (SMD = -0.21, 95%CI -0.37 to -0.05 ) of low back pain. There was low evidence of adverse effects (AEs) compared to placebo and low evidence of neurological AEs than placebo (relative risk = 1.93, 95%CI 1.41 to 2.64).Tanezumab, as a specific anti-NGF treatment, showed low evidence of a small to moderate effect for pain relief of low back pain (SMD = -0.44, 95%CI -0.81 to -0.07); and low evidence of a small effect for functional improvement (SMD = -0.26, 95%CI -0.40 to -0.12) with systemic administration, although not clinically significant. Tanezumab and anti-NGFs overall had, respectively, moderate and low evidence of overall AEs and serious AEs and a higher risk of developing neurological AEs when compared with placebo. Although anti-NGF, specifically tanezumab, showed a low-to-moderate effect on pain relief and functional improvement, it cannot be recommended for low back pain treatment. Without more research on the pathophysiology of anti-NGFs and adverse effects, its use is not safe in the overall population. However, as corroborated by the US Food and Drug Administration, this meta-analysis underscores a role for greater insight into anti-NGF therapy for painful conditions that are refractory to current drugs, such as oncologic pain, chronic pancreatitis, and phantom-limb pain. Given the pathophysiology of axial pain involving inflammatory mediators and the adverse effects of systemic anti-NGF use, consideration of local therapies may warrant further exploration. Key Words: back pain, anti-ngf, spine, sciatica, nerve growth factor, radiculopathy, treatment

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