Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective To further clarify the anatomical features of the long occipital nerve and summarize the rapid anatomical method for it,thus providing an operational basis for anatomists.Methods The bilateral sides of the head and neck specimens of 38 adult formalin-fixed cadavers were dissected,with a total of 76 specimens.The lateral cervical region,the sternocleidomastoid region,and the occipital region were dissected.The dissection focused on the long occipital nerve,the location and adjacent structural characteristics of which were carefully observed.Results The long occipital nerve was dissected out from 76 specimens.Through the posterior margin line(PML)anatomical method,the long occipital nerve was identified 1-3 cm above the accessory nerve,near the posterior border of the deep surface of the upper sternocleidomastoid in 70(92.1%)specimens.Through the inflection point(IP)anatomical method,the long occipital nerve was observed within the range of the circle with a radius of about 1.5 cm and centered on the midpoint of the line between the tip of the mastoid process and the tip of the external occipital protuberance in 6(7.9%)specimens.Conclusions The long occipital nerve can be quickly found by the PML method or IP method.Although the long occipital nerve can definitely be identified by the IP method,the anatomical operation is difficult.
Humans ; Cadaver ; Spinal Nerves/anatomy & histology* ; Neck/innervation* ; Adult

Our previous investigation suggested that faster seventh cervical nerve (C7) regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer. This finding needed further verification, and the mechanism remained largely unknown. Here, Tinel's test revealed faster C7 regeneration in patients with cerebral injury, which was further confirmed in mice by electrophysiological recordings and histological analysis. Furthermore, we identified an altered systemic inflammatory response that led to the transformation of macrophage polarization as a mechanism underlying the increased nerve regeneration in patients with cerebral injury. In mice, we showed that, as a contributing factor, serum amyloid protein A1 (SAA1) promoted C7 regeneration and interfered with macrophage polarization in vivo. Our results indicate that altered inflammation promotes the regenerative capacity of the C7 nerve by altering macrophage behavior. SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.
Animals ; Brachial Plexus ; Brachial Plexus Neuropathies/surgery* ; Humans ; Mice ; Nerve Transfer ; Peripheral Nerves ; Spinal Nerves

OBJECTIVE: To investigate the efficacy and safety of ultrasound-guided selective nerve branch blockage in the treatment of lumbar spinal nerve posterior branch syndrome. METHODS: A total of 40 patients with lumbar spinal nerve posterior branch syndrome treated by Pain Clinic from May 2017 to December 2018 were selected. According to the method used in locating site for nerve blockage, the patients were divided into ultrasound-guided group and anatomical positioning group, with 20 cases in each group. In anatomical positioning group, there were 7 males and 13 females, aged (63.42±7.71) years old, weighted (63.65±10.72) kg, numerical rating scale (NRS) was (6.61±1.52) scores, course of disease was (16.55±4.68) months. Pain sites:4 cases at L RESULTS: There were no statistically significant differences in gender, age, weight, NRS, course of disease and pain segment distribution between two groups ( CONCLUSION Comparedwith anatomicalpositioning, ultrasound-guided selective nerve branch block for the treatment of posterior branch of the lumbar spinal cord syndrome can reduce the number of treatments and maintain a longer therapeutic effect, but it is also necessary to pay attention to the time of each treatment to avoid dizziness and other adverse reactions.
Aged ; Female ; Humans ; Lumbosacral Region ; Male ; Middle Aged ; Nerve Block ; Spinal Nerves/diagnostic imaging* ; Ultrasonography ; Ultrasonography, Interventional

The ansa cervicalis is a neural loop in the neck formed by connecting the superior root from the cervical spinal nerves (C1–2) and the inferior root descending from C2–C3. It has various anatomical variations and can be an important acknowledgment in specific operations of the neck region. This is a review the anatomy, variations, pathology and clinical applications of the ansa cervicalis.
Hypoglossal Nerve ; Neck ; Pathology ; Spinal Nerves

STUDY DESIGN: A retrospective study. PURPOSE: The first research on the erector spinae plane (ESP) block was published in 2016. To our knowledge, no cohort studies or randomized controlled trials of the ESP block were performed in 2016 and 2017. OVERVIEW OF LITERATURE: This study retrospectively investigated the efficacy of the ESP block in pain management after lumbar spinal surgery. METHODS: Patients who underwent lumbar spinal surgery in 2017 were enrolled in the study. Those who underwent secondary surgery with local anesthesia other than the ESP block were excluded. The primary outcome was the Numerical Rating Scale (NRS) pain score at various time points until the morning of postoperative day 2. The secondary outcomes were the amount of intravenous fentanyl administered during the first 24 hours following the surgery and the number of patients with complaints of complications such as nausea and vomiting until the morning of postoperative day 2. RESULTS: The data of 41 patients undergoing lumbar spinal surgery were retrospectively analyzed. Of these, 23 received only general anesthesia (G group), whereas the other 18 patients received the ESP block in addition to general anesthesia (E group). The NRS pain scores and the amount of fentanyl administered were lower in the G group than in the E group at all measured time points (all data were less than p<0.05). There was no significant difference in the incidence of complications between the two groups (p=0.11). CONCLUSIONS: The ESP block provides effective postoperative analgesic effect for 24 hours in patients undergoing lumbar spinal surgery.
Anesthesia, General ; Anesthesia, Local ; Cohort Studies ; Fentanyl ; Humans ; Incidence ; Nausea ; Pain Management ; Retrospective Studies ; Spinal Nerves ; Vomiting

Neuroinflammation is one of the key mechanisms of neuropathic pain, which is primarily mediated by the Toll-like receptor 4 (TLR4) signaling pathways in microglia. Therefore, TLR4 may be a reasonable target for treatment of neuropathic pain. Here, we examined the analgesic effect of TLR4 antagonistic peptide 2 (TAP2) on neuropathic pain induced by spinal nerve ligation in rats. When lipopolysaccharide (LPS)-stimulated BV2 microglia cells were treated with TAP2 (10 µM), the mRNA levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS), were markedly decreased by 54–83% as determined by quantitative PCR (qPCR) analysis. Furthermore, when TAP2 (25 nmol in 20 µL PBS) was intrathecally administered to the spinal nerve ligation-induced rats on day 3 after surgery, the mechanical allodynia was markedly decreased for approximately 2 weeks in von Frey filament tests, with a reduction in microglial activation. On immunohistochemical and qPCR analyses, both the level of reactive oxygen species and the gene expression of the proinflammatory mediators, such as TNF-α, IL-1β, IL-6, COX-2, and iNOS, were significantly decreased in the ipsilateral spinal dorsal horn. Finally, the analgesic effect of TAP2 was reproduced in rats with monoiodoacetate-induced osteoarthritic pain. The findings of the present study suggest that TAP2 efficiently mitigates neuropathic pain behavior by suppressing microglial activation, followed by downregulation of neuropathic pain-related factors, such as reactive oxygen species and proinflammatory molecules. Therefore, it may be useful as a new analgesic for treatment of neuropathic pain.
Analgesics ; Animals ; Down-Regulation ; Gene Expression ; Hyperalgesia ; Interleukin-6 ; Interleukins ; Ligation ; Microglia ; Neuralgia ; Nitric Oxide Synthase Type II ; Polymerase Chain Reaction ; Prostaglandin-Endoperoxide Synthases ; Rats ; Reactive Oxygen Species ; RNA, Messenger ; Spinal Cord Dorsal Horn ; Spinal Nerves ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha

PURPOSE: Sacral nerve stimulation has been used to treat overactive bladder. This study evaluated the effects of stimulation using different pulse widths on the inhibition of bladder overactivity by sacral nerve stimulation (SNM) in pigs. METHODS: Implant-driven stimulators were used to stimulate the S3 spinal nerve in 7 pigs. Cystometry was performed by infusing normal saline (NS) or acetic acid (AA). SNM at pulse widths of 64 μsec to 624 μsec was conducted at the intensity threshold at which observable perianal and/or tail movement was induced. Multiple cystometrograms were performed to determine the effects of different pulse widths on the micturition reflex. RESULTS: AA-induced bladder overactivity reduced the bladder capacity to 46.9%±7.1% of the NS control level (P<0.05). During AA infusion, SNM at 64 μsec, 204 μsec, and 624 μsec increased the bladder capacity to 126.1%±6.9%, 129.5%±7.3%, and 140.1%±7.6% of the AA control level (P<0.05). No significant differences were found among the results obtained using pulse widths of 64 μsec, 204 μsec, and 624 μsec (P>0.05). The actual intensity threshold varied from 0.7 to 8 V. The mean intensity threshold (T visual) for pulse widths of 64 μs, 204 μs, and 624 μs were 5.64±0.76 V, 3.11±0.48 V, and 2.52±0.49 V. T visual for pulse widths of 64 μsec was larger than the other two T visual for pulse widths of 204 μsec and 624 μsec (P<0.05). No significant differences were found among the T visual for pulse widths of 204 μsec and 624 μsec (P>0.05). CONCLUSIONS: This study indicated that different pulse widths could play a role in inhibiting bladder overactivity. It is not yet certain which pulse widths increased bladder capacity compared with AA levels, to minimize energy consumption and maintain patient comfort during stimulation, 204 μsec may be an appropriate pulse width for SNM.
Acetic Acid ; Humans ; Reflex ; Spinal Nerves ; Swine ; Tail ; Urinary Bladder ; Urinary Bladder, Overactive ; Urination

The approach we suggest was developed for cases in which the fourth and fifth lumbar and first sacral spinal nerves were affected in lumbar degenerative disc disease. Retrodiscal transforaminal epidural injection is known to be very effective for lumbar radiculopathy because of excellent access to primary pathology; however, access below L5 is often restricted by the anatomic characteristics of the L5–S1. In the translateral recess approach (TLR), proper final needle placement (i.e., in the axillary portion between the exiting and traversing nerve roots) can be achieved by setting the direction of the needle laterally and superiorly from the distal tip of the infra-adjacent spinous process toward the medial wall of the pedicle and neural foramen of the given level without neural injury. This approach is possible because of the wide interlaminar space in the L5–S1. Preganglionic epidural injection through TLR is an effective and safe spinal intervention for lumbosacral radiculopathy.
Injections, Epidural ; Needles ; Pathology ; Radiculopathy ; Spinal Nerves

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
Adenosine ; Amitriptyline ; Animals ; Antidepressive Agents, Tricyclic ; Cyclic AMP Response Element-Binding Protein ; Cytokines ; Humans ; Hyperalgesia ; Immunoblotting ; Ligation ; Male ; Neuralgia ; Phosphotransferases ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 ; Spinal Nerves