Cervical Discs as a Source of Neck Pain. An Analysis of the Evidence.

OBJECTIVESBACKGROUND: Objectives To determine the extent and strength of evidence that supports the belief that cervical intervertebral discs are a source of neck pain. DESIGN: Design The evidence from anatomical, laboratory, experimental, diagnostic, and treatment studies was summarized and analyzed for concept validity, face validity, content validity, and construct validity. RESULTS: Results Evidence from basic sciences shows that cervical discs have a nociceptive innervation, and experimental studies show that they are capable of producing neck pain. Disc stimulation has been developed as a diagnostic test but has rarely been used in a disciplined fashion. The prevalence of cervical disc pain has not been properly established but appears to be low. No treatment has been established that reliably achieves complete relief of neck pain in substantial proportions of patients. CONCLUSIONS: Conclusions Basic science evidence supports the concept of cervical disc pain, but epidemiologic and clinical evidence to vindicate the clinical application of the concept is poor or lacking.

Ingrowth of Nociceptive Receptors into Diseased Cervical Intervertebral Disc Is Associated with Discogenic Neck Pain.

OBJECTIVE: To investigate the distribution of nociceptive nerve fibers in the cervical intervertebral discs of patients with chronic neck pain and determine whether these nociceptive nerve fibers are related to discogenic neck pain. METHODS: We collected 43 samples of cervical intervertebral discs from 34 patients with severe chronic neck pain (visual analog scale [VAS] ≥ 70 mm), 42 samples from 36 patients who suffered cervical spondylotic radiculopathy or myelopathy without neck pain or with mild neck pain (VAS ≤ 30 mm) and 32 samples from eight donators to investigate their innervation immunohistochemically using an antibody against neuropeptide substance P. RESULTS: The immunohistochemical investigation revealed that substance P-positive nerve fibers were obviously increased in number and deeply ingrown into the inner anulus fibrosus and even into the nucleus pulposus in the degenerative cervical discs of patients with severe neck pain in comparison with the discs of patients with cervical spondylotic radiculopathy or myelopathy and normal control discs (P<0.01). CONCLUSIONS: The current study may indicate a key role of nociceptive nerve fibers in the pathogenesis of neck pain of cervical disc origin.

Reverse Reconstruction and Bioprinting of Bacterial Cellulose-Based Functional Total Intervertebral Disc for Therapeutic Implantation.

The degradation of intervertebral discs (IVD), a typical hierarchical structured tissue, causes serious neck and back pain. The current methods cannot fully reconstitute the unique structure and function of native IVD. In this study, by reverse reconstruction of the structure of native IVD and bioprinting bacterial cellulose (BC) nanofibers with a high-throughput optimized micropattern screening microchip, a total IVD is created that contained type II collagen-based nucleus pulposus (NP) and hierarchically organized and micropatterned BC-based annulus fibrosus (AF), mimicking native IVD tissue. The artificial NP contains rat NP cells, whereas the AF contains concentrically arranged BC layers with aligned micropatterns and attached AF cells in +/-30° alternate directions between adjacent layers. Long-term (3 months) implantation experiments on rats demonstrate the excellent structural (shape maintenance, hydration, tissue integration) and functional (mechanical support and flexibility) performance of the artificial IVD. This study provides a novel strategy for creating highly sophisticated artificial tissues.

[Clinical outcomes for Bioflex system in the treatment of lumbar degenerative disease].

OBJECTIVE: To evaluate the clinical outcomes of Biofelx dynamic stabilization system in the treatment of lumbar degenerative disease (LDD). METHODS: A total of 29 patients (16 males, 13 females) received the treatment of Bioflex between June 2011 and April 2013 were recruited. There were with lumbar spinal stenosis (n = 15), lumbar disc herniation (n = 10) and lumbar spondylolisthesis (n = 4). And they underwent one-segment (n = 14), two-segment (n = 10), three-segment (n = 3) and four-segment (n = 2) implantations. Mean age was 52.3 (38-62) years. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical outcomes. And lumbar radiography was used to observe disc height (DH) and range of motion (ROM) in fixed segment and cranial adjacent segment before and after operation. RESULTS: The mean follow-up period was 22.6 ± 2.1 (8-32) months. The mean ODI score decreased from 39.96 ± 2.58 preoperatively to 11.26 ± 1.76 at 3 months postoperatively (P < 0.05) and 3.97 ± 1.30 at the last follow-up (P < 0.05). The mean VAS score for low back pain dropped from 7.34 ± 0.80 preoperatively to 2.63 ± 1.01 at 3 months postoperatively (P < 0.05) and 0.91 ± 0.32 at the last follow-up (P < 0.05). The mean VAS score for leg pain deceased from 8.63 ± 0.95 preoperatively to 2.13 ± 0.62 at 3 months postoperatively and 0.58 ± 0.65 at the last follow-up (P < 0.05). The implanted segment preserved some ROM at the last follow-up. Compared to preoperative, no statistically significance existed in postoperative DH and ROM (P > 0.05). CONCLUSION: The clinical outcomes of Bioflex system are excellent in the treatment of LDD. As an effective therapy for non-fusion of LDD, it may preserve some ROM of fixed segment and prevent increased range of motion in adjacent segment.

Intervertebral disc injury triggers neurogenic inflammation of adjacent healthy discs.

BACKGROUND CONTEXT: Intervertebral disc degeneration is common and may play an important role in low back pain, but it is not well-understood. Previous studies have shown that the outer layer of the annulus fibrosus of a healthy disc is innervated by nociceptive nerve fibers. In the process of disc degeneration, it can grow into the inner annulus fibrosus or nucleus pulposus and release neuropeptides. Disc degeneration is associated with inflammation that produces inflammatory factors and potentiates nociceptor sensitization. Subsequently neurogenic inflammation is induced by neuropeptide release from activated primary afferent terminals. Because the innervation of a lumbar disc comes from multi-segmental dorsal root ganglion neurons, does neurogenic inflammation in a degenerative disc initiate neurogenic inflammation in neighboring healthy discs by antidromic activity? PURPOSE: This study was based on animal experiments in Sprague-Dawley rats to investigate the role of neurogenic inflammation in adjacent healthy disc degeneration induced by disc injury. STUDY DESIGN: This was an experimental study. METHODS: Seventy-five 12-week-old, male Sprague-Dawley rats were allocated to 3 groups (sham group, disc injury group and disc injury+TrkA antagonist group). The disc injury group was punctured in the tail disc between the eighth and ninth coccygeal vertebrae (Co8-9) to establish an animal model of tail intervertebral disc degeneration. The sham group underwent only skin puncture and the disc injury+TrkA antagonist group was intraperitoneally injected with GW441756 two days before disc puncture. The outcome measure included quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Disc injury induced an increase in aggrecan, NGF, TrkA, CGRP, SP, IL-1ß, and IL-6 mRNA levels in the injured (Co8-9) and adjacent discs (Co7-8), which reached a peak on day 1, then gradually decreased, and returned to normal on day 14. After intraperitoneal injection of GW441756 prior to puncture, the mRNA levels of the above indicators were down-regulated in Co7-8 and Co8-9 intervertebral discs on the 1st and 7th days. The protein content of the above indicators in Co7-8 and Co8-9 intervertebral discs showed roughly the same trend as mRNA levels. CONCLUSIONS: Degeneration of one disc can induce neurogenic inflammation of adjacent healthy discs in a rat model. CLINICAL SIGNIFICANCE: This model supports a key role of neurogenic inflammation in disc degeneration, and may play a role in the experience of low back pain.

Phosphoglycerate mutase 5 facilitates mitochondrial dysfunction and neuroinflammation in spinal tissues after spinal cord injury.

Spinal cord injury (SCI) is a high incidence worldwide that causes a heavy physical and psychological burden to patients. It is urgent to further reveal the pathological mechanism and effective treatment of SCI. Mitochondrial dysfunction plays an important role in the disease progression of SCI. As a mitochondrial membrane protein, phosphoglycerate mutase 5 (PGAM5) is mainly involved in mitochondrial function and mitosis to modulate cellular physiological functions, but the roles of PGAM5 in spinal tissues remain to be unreported after SCI. The purpose of this study was to evaluate the role of PGAM5 in SCI mice and its relationship with neuroinflammation. The results showed that the mitochondrial membrane protein PGAM5 was involved in microglia activation after SCI, and PGAM5 deletion could improve mitochondrial dysfunction (including abnormal mtDNA, ATP synthases, and ATP levels, Cyt C expression, and ROS and rGSH levels) in spinal cord tissue after SCI, Arg1/iNOS mRNA level, iNOS expression, and pro-inflammatory cytokines TNF-α, IL-1ß, and IL-18 levels. In vitro, H2O2 increased TNF-α, IL-1ß, and IL-18 levels in BV2 cells, and PGAM5-sh and Nrf2 activators significantly reversed H2O2-induced iNOS expression and proinflammatory cytokine production. Furthermore, IP/Western blotting results revealed that PGAM5-sh treatment significantly reduced the interaction of PGAM5 with Nrf2 and enhanced the nuclear translocation of Nrf2 in BV2 cells. The data suggested that PGAM5 was involved in the cascade of oxidative stress and inflammatory response in microglia via facilitating the expression level of Nrf2 in the nucleus after SCI. It provided a reference for clarifying the pathological mechanism and therapeutic target of SCI.

Patient-Reported Outcome Measures following Coblation Nucleoplasty for Cervical Discogenic Dizziness.

BACKGROUND: There is little research in the literature comparing the efficacy of coblation nucleoplasty with conservative treatment in the treatment of cervical discogenic dizziness and reporting the achieved rate of minimal clinically important differences (MCID) and patient acceptable symptom state (PASS) after surgery. This retrospective study aims to explore the patient-reported outcome measures (PROM) following coblation nucleoplasty for cervical discogenic dizziness and to compare the therapeutic effect of coblation nucleoplasty with prolonged conservative treatment. METHODS: Sixty-one patients with cervical discogenic dizziness and a positive intradiscal diagnostic test eligible for single-level cervical coblation nucleoplasty were included in the study. Among these 61 patients, 40 patients underwent cervical coblation nucleoplasty, while the remaining 21 patients refused surgery and received continued conservative treatment. The primary PROMs were the intensity and frequency of dizziness and secondary PROMs were related to the neck disability index (NDI) and visual analog scale (VAS) for neck pain (VAS-neck) during a 12-month follow-up period. Moreover, the achieved rate of MCID and PASS in both groups was assessed 12 months after surgery. RESULTS: Dizziness intensity, dizziness frequency, VAS-neck score, and NDI score were significantly improved from the baseline at all follow-up time points in both treatment groups, except for showing no significant improvement in dizziness frequency in the conservative treatment group at 6 and 12 months after surgery. However, at each follow-up time point, the above indexes were lower in the surgery group than in the conservative treatment group. In addition, the achieved rates for PASS and MCID in all indexes in the surgery group were significantly higher than those in the conservative treatment group at 12 months after surgery. CONCLUSIONS: Cervical coblation nucleoplasty significantly improved the intensity and frequency of dizziness, neck pain, and NDI in patients with cervical discogenic dizziness, and the results were superior to those from prolonged conservative treatment. Meanwhile, cervical coblation nucleoplasty is a good choice for patients with chronic neck pain and refractory cervical discogenic dizziness who have not demonstrated the indications for open surgery and have not responded well to conservative treatment.

Anterior Cervical Decompression and Fusion Surgery for Cervical Spondylosis with Concomitant Tinnitus: A Multicenter Prospective Cohort Study.

OBJECTIVE: Cervical spondylosis is often accompanied by tinnitus. Up to now, there is a lack of large samples and prospective studies to investigate the effect of anterior cervical decompression and fusion (ACDF) on tinnitus associate with cervical spondylosis. To this end, we performed a prospective cohort study to assess the effectiveness of ACDF on the relief of tinnitus. METHODS: This was a multicenter, prospective, cohort clinical study. Between August 2017 and August 2018, 174 patients with cervical spondylosis accompanied by tinnitus were enrolled, with a follow-up of 12 months. Among the 174 patients, 142 received anterior cervical surgery (surgery group) and 32 received conservative treatment (conservative group). The primary end point was the mean change in scores on the tinnitus functional index (TFI). The secondary end points included tinnitus loudness, modified Japanese orthopaedic association scores (mJOA) for spinal cord function, and visual analogue scale (VAS) for neck pain. All the above indexes were measured before treatments and at 1, 3, 6, and 12 months after treatments. One-way analysis of variance and paired samples t-test was adopted for statistical analysis. RESULTS: The TFI score was reduced immediately after cervical decompression surgery (from 54.7 ± 15.6 to 32.3 ± 12.5, P < 0.001) and this was sustained at 12 months (P < 0.001). The TFI score of the conservative group also decreased (from 53.9 ± 16.8 to 45.2 ± 13.6, P < 0.001), but the effect was not maintained at 12 months (P = 0.069). There was a significant improvement in tinnitus loudness (from 5.2 ± 1.6 to 2.6 ± 1.9, P < 0.001), mJOA (from 12.0 ± 1.6 to 14.2 ± 1.6, P < 0.001), and VAS for neck pain (from 58.5 ± 9.6 to 22.0 ± 16.4, P < 0.001) in the surgical group. Improvements in the surgical group were statistically significantly greater than that in the conservative group (P < 0.001). CONCLUSION: This study indicates that anterior cervical surgery can relieve tinnitus in patients with cervical spondylosis and that tinnitus is an accompanying manifestation of cervical spondylosis.

Testicular pain originating from lumbar disc degeneration: A case report.

BACKGROUND: Testicular pain caused by lumbar disease is uncommon in the clinic. Here we reported a case of discogenic low back pain with testicular pain that was successfully cured. CASE SUMMARY: A 23-year-old male patient presented to our department with chronic low back pain. Based on his clinical symptoms, signs and imaging, he was diagnosed with discogenic low back pain. Since conservative treatment for more than half a year did not significantly improve his low back pain, we decided to treat it with intradiscal methylene blue injection. During the course of surgery, we again identified the low back pain as originating from the degenerated lumbar disc by analgesic discography. Interestingly, the patient's low back pain disappeared along with the testicular pain that had been present for more than 3 mo. After the operation, the patient's low back pain improved, and the testicular pain did not reappear. CONCLUSION: Intradiscal methylene blue injection is a convenient and effective surgical intervention for the treatment of discogenic low back pain. Lumbar disc degeneration may also be a possible clinical cause of testicular pain. Methylene blue injection in the diseased disc improved the low back pain, and the accompanying testicular pain was successfully managed.

Barriers to mesenchymal stromal cells for low back pain.

Intervertebral disc degeneration is the main cause of low back pain. In the past 20 years, the injection of mesenchymal stromal cells (MSCs) into the nucleus pulposus of the degenerative disc has become the main approach for the treatment of low back pain. Despite the progress made in this field, there are still many barriers to overcome. First, intervertebral disc is a highly complex load-bearing composite tissue composed of annulus fibrosus, nucleus pulposus and cartilaginous endplates. Any structural damage will change its overall biomechanical function, thereby causing progressive degeneration of the entire intervertebral disc. Therefore, MSC-based treatment strategies should not only target the degenerated nucleus pulposus but also include degenerated annulus fibrosus or cartilaginous endplates. Second, to date, there has been relatively little research on the basic biology of annulus fibrosus and cartilaginous endplates, although their pathological changes such as annular tears or fissures, Modic changes, or Schmorl's nodes are more commonly associated with low back pain. Given the high complexity of the structure and composition of the annulus fibrosus and cartilaginous endplates, it remains an open question whether any regeneration techniques are available to achieve their restorative regeneration. Finally, due to the harsh microenvironment of the degenerated intervertebral disc, the delivered MSCs die quickly. Taken together, current MSC-based regenerative medicine therapies to regenerate the entire disc complex by targeting the degenerated nucleus pulposus alone are unlikely to be successful.

Proprioceptive Cervicogenic Dizziness: A Narrative Review of Pathogenesis, Diagnosis, and Treatment.

Basic science and clinical evidence suggest that cervical spine disorders can lead to dizziness. The cervical spine has highly developed proprioceptive receptors, whose input information is integrated with the visual and vestibular systems in the central nervous system, acting on the neck and eye muscles to maintain the coordinative motion of the head, eyes, neck, and body through various reflex activities. When the cervical proprioceptive input changes due to the mismatch or conflict between vestibular, visual, and proprioceptive inputs, cervicogenic dizziness may occur. The diagnosis of cervicogenic dizziness can be determined based on clinical features, diagnostic tests, and the exclusion of other possible sources of dizziness. The cervical torsion test appears to be the best diagnostic method for cervicogenic dizziness. Based on the available evidence, we first developed the diagnostic criteria for cervicogenic dizziness. Treatment for cervicogenic dizziness is similar to that for neck pain, and manual therapy is most widely recommended.

Analysis of injury and pain scores during fusion surgery for multisegmental lumbar spinal stenosis in elderly patients.

INTRODUCTION: Lumbar stenosis has become a common disease. Controversies exist regarding fusion surgery. MATERIAL AND METHODS: The patients were divided into groups per the method of fusion received: the posterolateral fusion group (group P) and the intervertebral fusion group (group I). The patients were further divided into groups based on the number of fusion segments: the 2-segment group (P2 and I2), the 3-segment group (P3 and I3), and the 4-segment group (P4 and I4). The operative time, intraoperative blood loss, blood transfusion volume, and postoperative drainage volume were summarized. In particular, wound healing appearance and management were observed. RESULTS: The operation time and blood transfusion volume of the P2 and P3 groups were significantly less than those of the I2 and I3 groups (p < 0.05). The postoperative drainage volume of group I4 was less than that of group P4 (p < 0.05). Postoperative numeric rating scale (NRS) scores of P2 and P3 groups were lower than those of I2 and I3 groups (p < 0.05), while the NRS scores of P4 group were higher than those of I4 group (p < 0.05). CONCLUSIONS: Posterolateral and intervertebral fusion techniques can be used in the surgical treatment of elderly patients with lumbar spinal stenosis. The posterolateral fusion method should be used when three or fewer segments require surgery. The intervertebral fusion method should be used when four segments require surgery.

Application of a new anatomic hook-rod-pedicle screw system in young patients with lumbar spondylolysis: A pilot study.

BACKGROUND: The pedicle screw-laminar hook system has strong fixation and is conducive to bone graft fusion for lumbar spondylolysis. However, the current pedicle screw-laminar hook fixation system is not specifically designed for lumbar spondylolysis. AIM: To investigate the clinical effects of a new anatomical hook-rod-pedicle screw system in the treatment of lumbar spondylolysis in young adults. METHODS: We designed a new anatomic hook-rod-pedicle screw system for young patients with lumbar spondylolysis. The isthmus and the corresponding pedicle screw entry point were exposed through the intermuscular approach. Autogenous iliac bone graft was obtained to bridge the isthmus defect, and then the anatomic hook-rod-pedicle screw system was used to fix the isthmus in 15 young patients. RESULTS: At 24 mo follow-up, the visual analogue scale score of low back pain decreased from 6.73 ± 0.88 to 0.73 ± 0.59, and the Oswestry disability index score decreased from 58.20 ± 8.99 to 7.87 ± 4.97. Computed tomography showed bilateral isthmic bone healing in 14 cases and unilateral isthmic bone healing in 1 case. Magnetic resonance imaging showed that the lumbar disc signal of diseased segment and adjacent segments had no change compared with that before surgery. The pain visual analogue scale score of the donor site was 0.20 ± 0.41 at the last follow-up. According to the Modified Macnab score, the excellent and good rate was 100%. CONCLUSION: The application of this new anatomical hook-rod-pedicle screw system to treat young patients with lumbar spondylolysis has the advantages of less trauma, a simple operation and satisfactory clinical effects.

Anterior cervical decompression and fusion surgery for cervicogenic headache: A multicenter prospective cohort study.

Background: Cervicogenic headache (CEH) has long been recognized as a referred pain deriving from pathological changes in the upper cervical nerves. However, previous clinical studies found that anterior lower cervical discectomy for the treatment of cervical myelopathy and/or radiculopathy can also help relieve associated headaches. To date, there is still a lack of large sample and prospective study to investigate the effect of anterior cervical decompression and fusion (ACDF) on CEH associated with cervical spondylosis. Methods: A total of 656 patients with cervical radiculopathy and/or myelopathy were enrolled in three spinal centers. Among them, 221 patients who were diagnosed with CEH were collected in this study, and 204 completed a 1-year follow-up. The primary endpoint was headache intensity during a 12-month follow-up period measured by the numeric pain rating scale (NPRS). The secondary outcome measures included headache frequency, headache duration, and the neck disability index (NDI). Results: Among all 204 patients with CEH who completed a 1-year follow-up, 166 received anterior cervical surgery (surgery group) and 38 received conservative treatment (conservative group). There were statistically significant lower NPRS in the surgical group during follow-up. Between-group differences showed that NPRS in the surgery group was significantly greater improvement at 1 month (2.8, 95% CI: 2.0, 3.6), 3 months (2.6, 95% CI: 1.8, 3.4), 6 months (2.4, 95% CI: 1.6, 3.2), and 12 months (1.5, 95% CI: 0.7, 2.4) (p < 0.05 for all). There were statistically significant lower NDI, less frequent headaches, and lower headache duration in the surgery group during follow-up (p < 0.05 for all). Conclusion: This study indicates that ACDF can effectively relieve CEH associated with cervical myelopathy and/or radiculopathy.

Editorial for the special issue of the Chinese Association for the Study of Pain.

The Ministry of Health of China officially issued a document, adding the first level diagnosis and treatment discipline "Algology" in the list of diagnosis and treatment subjects of medical institutions on July 16, 2007. As the most important pain academic organization in China, the Chinese Association for the Study of Pain has made outstanding contributions in promoting the development of pain discipline and in establishing pain standards and disease diagnosis and treatment guidelines. In this special issue, under the leadership of Yan-Qing Liu, Chairman of the 7th Committee of the Chinese Association for the Study of Pain, nine consensus and one guideline were included.

Surgical treatment of four segment lumbar spondylolysis: A case report.

BACKGROUND: Four-level lumbar spondylolysis is extremely rare. So far, only 1 case has been reported in the literature. CASE SUMMARY: A 19-year-old man presented with severe back pain irresponsive to conservative therapies for 2 years. Lumbar radiographs and two-dimensional computed tomography scan showed four segment lumbar spondylolysis on both sides of L2-L5. Lumbar magnetic resonance imaging showed normal signal in all lumbar discs. Because daily activities were severely limited, surgery was recommended for the case. The patient underwent four-level bilateral isthmic repair at L2-L5. During surgery, L2-L5 isthmi were curetted bilaterally, freshened, and then grafted with autologous iliac bone that was bridged and compressed with a pedicular screw connected to a sub-laminar hook by a short rod. The symptoms of back pain almost disappeared. He has been followed-up for 96 mo, and his symptoms have never recurred. Fusion was found in all repaired isthmi 14 mo after surgery according to evaluation of lumbar radiography and computed tomography scan. CONCLUSION: We report here 1 case of four-level lumbar spondylolysis that was treated successfully with direct isthmic repair.

Cervical Proprioception Impairment in Neck Pain-Pathophysiology, Clinical Evaluation, and Management: A Narrative Review.

Neck pain is very common, but most of the causes are unknown, making diagnosis and treatment extremely challenging. Current studies have found that one of the main problems in patients with neck pain is the impairment of cervical proprioception, which subsequently leads to cervical sensorimotor control disturbances. Cervical spine has a very delicate proprioceptive system that plays a crucial role in controlling posture and balance. Cervical proprioceptive impairment in neck pain occurs through a variety of mechanisms. Experimental neck muscle pain induced by injection of hypertonic saline results in inhibition of the activation of painful muscle; chronic neck pain causes structural and functional impairment of cervical muscles; excessive activation of mechanoreceptors in degenerative cervical discs and facet joints produces a large number of erroneous sensory signals. Clinical examinations to assess the link between structural pathology and neck pain have been unsuccessful, opening the way for the development of function-based tests. To date, eight neck sensorimotor control tests have been reported to evaluate patients with chronic neck pain. Although some tests may involve different subsystems (such as oculomotor system and vestibular system), all tests measure sensorimotor control in the neck, and the most commonly used is cervical joint position error (JPE) test. Current studies support the effectiveness of exercises targeting different aspects of sensorimotor function, in particular retraining aimed at improving cervical proprioception and muscle coordination. Based on the available evidence, it is recommended that patients with neck pain should be assessed and managed for cervical proprioceptive impairment and sensorimotor control disturbances.

Cervical intervertebral disc degeneration and dizziness.

Clinical studies have found that patients withcervical degenerative disease are usually accompanied by dizziness. Anterior cervical surgery can eliminate not only chronic neck pain, cervical radiculopathy or myelopathy, but also dizziness. Immunohistochemical studies show that a large number of mechanoreceptors, especially Ruffini corpuscles, are present in degenerated cervical discs. The available evidence suggests a key role of Ruffini corpuscles in the pathogenesis of dizziness caused by cervical degenerative disease (i.e. cervical discogenic dizziness). Disc degeneration is characterized by an elevation of inflammatory cytokines, which stimulates the mechanoreceptors in degenerated discs and results in peripheral sensitization. Abnormal cervical proprioceptive inputs from the mechanoreceptors are transmitted to the central nervous system, resulting in sensory mismatches with vestibular and visual information and leads to dizziness. In addition, neck pain caused by cervical disc degeneration can play a key role in cervical discogenic dizziness by increasing the sensitivity of muscle spindles. Like cervical discogenic pain, the diagnosis of cervical discogenic dizziness can be challenging and can be made only after other potential causes of dizziness have been ruled out. Conservative treatment is effective for the majority of patients. Existing basic and clinical studies have shown that cervical intervertebral disc degeneration can lead to dizziness.

Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury.

Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI. Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage. Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1ß and IL-18 levels, and NLRP3 expression. Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.