-
Brain and Behavior Dec 2018Contralateral cervical seventh nerve root (CC7) transfer has been widely applied for treatment of traumatic brachial plexus injury. The purpose of the study was to...
INTRODUCTION
Contralateral cervical seventh nerve root (CC7) transfer has been widely applied for treatment of traumatic brachial plexus injury. The purpose of the study was to evaluate outcomes of patients with global brachial plexus avulsion (GBPA) after CC7 transfer and compare the recoveries of median nerve as the only recipient nerve and one of the multiple recipient nerves.
METHODS
A retrospective review of 51 patients treated with CC7 transfers after GBPA was carried out. The British Medical Research Council (MRC) grading system and range of joint motion (ROM) were used for motor and sensory assessment.
RESULTS
The effective rates of FCR were 57.7%, 45.5%, and 36.4% in CC7 transfer to median nerve (CC7-Md), CC7 transfer to median nerve and biceps branch (CC7-Md+Bic) and CC7 transfer to median nerve and triceps branch (CC7-Md+Tric) groups, respectively. There were no statistical differences no matter in FCR or FDS among groups. The effective rate in biceps had no significant difference with that in triceps. The effective sensory recovery rate was 65.4%, 54.5%, and 36.4% in CC7-Md, CC7-Md+Bic, and CC7-Md+Tric groups. There were no statistical differences in the sensory effective recovery rate among groups. All the ROMs were improved significantly after surgery. The improvement of ROM of elbow flexion after surgery in CC7-Md+Bic group was significantly larger than that of elbow extension after surgery in CC7-Md+Tric group (p = 0.047).
CONCLUSIONS
The CC7 transfer contributed to the functional improvement of the hand and wrist for the patients with global brachial plexus avulsion. The whole CC7 could be used to repair more than one recipient nerve (including median nerve) without affecting the recovery of median nerve. When CC7 was used to repair two nerves, biceps branch might be preferred to choose as one recipient nerve rather than triceps branch.
Topics: Adolescent; Adult; Brachial Plexus; Cervical Vertebrae; Female; Hand; Humans; Male; Median Nerve; Middle Aged; Muscle, Skeletal; Nerve Transfer; Retrospective Studies; Spinal Nerve Roots; Transplant Recipients; Treatment Outcome; Wrist; Young Adult
PubMed: 30565875
DOI: 10.1002/brb3.1174 -
Yonsei Medical Journal Mar 2013Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation...
PURPOSE
Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats.
MATERIALS AND METHODS
Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 μg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP).
RESULTS
Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 μg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 μg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 μg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP.
CONCLUSION
Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.
Topics: Animals; Astrocytes; Disease Models, Animal; Hyperalgesia; Infusions, Spinal; Lamotrigine; Ligation; Male; Microglia; Neuralgia; Rats; Rats, Sprague-Dawley; Spinal Nerves; Triazines; Voltage-Gated Sodium Channel Blockers
PubMed: 23364963
DOI: 10.3349/ymj.2013.54.2.321 -
Spinal Cord Series and Cases 2019Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. The clinical spectrum of ECD is diverse, varying from asymptomatic focal lesion to... (Review)
Review
INTRODUCTION
Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. The clinical spectrum of ECD is diverse, varying from asymptomatic focal lesion to life-threatening multisystem infiltration. Neurological manifestations of ECD are common, mostly due to the involvement of the central nerve system. However, spinal nerve or peripheral nerve involvement has rarely been mentioned.
CASE PRESENTATION
Herein, we present a case of a 32-year-old female patient complaining about radiating pain on the front and lateral side of her left thigh for 2 months. Spinal MRI with contrast enhancement showed a space-occupying lesion on the left L3/L4 intervertebral foramen, indicating an initial diagnosis of lumbar nerve schwannoma. The patient underwent surgery to remove the mass and decompress the lumbar nerve. Postoperative histological examination revealed the diffuse infiltration of foamy histiocytes that were CD68, CD163, and CD1a on immunostaining, which confirmed the diagnosis of Erdheim-Chester disease. The radiating pain was gradually alleviated and PET-CT was performed but showed no further involvement of ECD.
DISCUSSION
To the best of our knowledge, this is the first case of ECD demonstrated as an infiltrative mass on the spinal nerve, with imaging manifestations and compression symptoms similar to those of peripheral nerve schwannoma.
Topics: Adult; Diagnosis, Differential; Erdheim-Chester Disease; Female; Humans; Lumbar Vertebrae; Neurilemmoma; Spinal Nerves
PubMed: 31700688
DOI: 10.1038/s41394-019-0234-4 -
Molecular Pain Sep 2009After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic...
Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury.
BACKGROUND
After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK) in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX) to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1) positive fibers (mostly C- and Adelta-fibers) and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI), and observed spinal microglial changes 2 days later.
RESULTS
SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+) were microglia (Iba1+). Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord.
CONCLUSION
(1) Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers) is not enough to prevent nerve injury-induced spinal microglial activation. (2) Peripheral input from large myelinated fibers is important for microglial activation. (3) Microglial activation is associated with mechanical allodynia.
Topics: Animals; Bromodeoxyuridine; Bupivacaine; Diterpenes; Enzyme Activation; Hot Temperature; Microglia; Microspheres; Motor Activity; Nerve Block; Nerve Fibers; Nociceptors; Pain; Phosphorylation; Proprioception; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Nerves; p38 Mitogen-Activated Protein Kinases
PubMed: 19772627
DOI: 10.1186/1744-8069-5-53 -
Molecular Pain Dec 2009Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic...
BACKGROUND
Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic pain are allodynia, hyperalgesia and spontaneous pain. Such abnormalities associated with neuropathic pain state remain to be a significant clinical problem. However, the neuronal mechanisms underlying the pathogenesis of neuropathic pain are complex and still poorly understood. Casein kinase 1 is a serine/threonine protein kinase and has been implicated in a wide range of signaling activities such as cell differentiation, proliferation, apoptosis, circadian rhythms and membrane transport. In mammals, the CK1 family consists of seven members (alpha, beta, gamma1, gamma2, gamma3, delta, and epsilon) with a highly conserved kinase domain and divergent amino- and carboxy-termini.
RESULTS
Preliminary cDNA microarray analysis revealed that the expression of the casein kinase 1 epsilon (CK1epsilon) mRNA in the spinal cord of the neuropathic pain-resistant N- type Ca2+ channel deficient (Cav2.2-/-) mice was decreased by the spinal nerve injury. The same injury exerted no effects on the expression of CK1epsilon mRNA in the wild-type mice. Western blot analysis of the spinal cord identified the downregulation of CK1epsilon protein in the injured Cav2.2-/- mice, which is consistent with the data of microarray analysis. However, the expression of CK1epsilon protein was found to be up-regulated in the spinal cord of injured wild-type mice. Immunocytochemical analysis revealed that the spinal nerve injury changed the expression profiles of CK1epsilon protein in the dorsal root ganglion (DRG) and the spinal cord neurons. Both the percentage of CK1epsilon-positive neurons and the expression level of CK1epsilon protein were increased in DRG and the spinal cord of the neuropathic mice. These changes were reversed in the spinal cord of the injured Cav2.2-/- mice. Furthermore, intrathecal administration of a CK1 inhibitor IC261 produced marked anti-allodynic and anti-hyperalgesic effects on the neuropathic mice. In addition, primary afferent fiber-evoked spinal excitatory responses in the neuropathic mice were reduced by IC261.
CONCLUSIONS
These results suggest that CK1epsilon plays important physiological roles in neuropathic pain signaling. Therefore CK1epsilon is a useful target for analgesic drug development.
Topics: Animals; Calcium Channels, N-Type; Casein Kinase 1 epsilon; Disease Models, Animal; Down-Regulation; Enzyme Activation; Enzyme Inhibitors; Ganglia, Spinal; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuralgia; Nociceptors; Organ Culture Techniques; Peripheral Nervous System Diseases; Posterior Horn Cells; RNA, Messenger; Spinal Cord; Spinal Nerve Roots; Spinal Nerves; Up-Regulation
PubMed: 20021638
DOI: 10.1186/1744-8069-5-74 -
Scientific Reports Sep 2019Patients suffer bilateral sacral plexus injuries experience severe problems with incontinence. We performed a cadaveric study to explore the anatomical feasibility of...
Patients suffer bilateral sacral plexus injuries experience severe problems with incontinence. We performed a cadaveric study to explore the anatomical feasibility of transferring ipsilateral S2 nerve root combined with a sural nerve graft to pudendal nerve for restoration of external anal and urethral sphincter function. The sacral nerve roots and pudendal nerve roots on the right side were exposed in 10 cadavers. The length from S2 nerve root origin to pudendal nerve at inferior border of piriformis was measured. The sural nerve was used as nerve graft. The diameters and nerve cross-sectional areas of S2 nerve root, pudendal nerve and sural nerve were measured and calculated, so as the number of myelinated axons of three nerves on each cadaver specimen. The length from S2 nerve root to pudendal nerve was 10.69 ± 1.67 cm. The cross-sectional areas of the three nerves were 8.57 ± 3.03 mm for S2, 7.02 ± 2.04 mm for pudendal nerve and 6.33 ± 1.61 mm for sural nerve. The pudendal nerve contained approximately the same number of axons (5708 ± 1143) as the sural nerve (5607 ± 1305), which was a bit less than that of the S2 nerve root (6005 ± 1479). The S2 nerve root in combination with a sural nerve graft is surgically feasible to transfer to the pudendal nerve for return of external urethral and anal sphincter function, and may be suitable for clinical application in patients suffering from incontinence following sacral plexus injuries.
Topics: Adult; Anal Canal; Feasibility Studies; Fecal Incontinence; Female; Humans; Male; Pudendal Nerve; Spinal Nerve Roots; Sural Nerve; Urethra; Urinary Incontinence
PubMed: 31570751
DOI: 10.1038/s41598-019-50484-7 -
Molecular Pain 2019Millions of people suffered from neuropathic pain, which is related to neuroinflammation in the central nervous system. Penehyclidine hydrochloride is a premedication of...
BACKGROUND
Millions of people suffered from neuropathic pain, which is related to neuroinflammation in the central nervous system. Penehyclidine hydrochloride is a premedication of general anesthesia, which has been confirmed possessing neuroprotective effects against various neurodegenerative or neuroinflammatory diseases. However, it is not clear that whether penehyclidine hydrochloride could suppress neuropathic pain through its anti-neuroinflammatory effects.
METHODS
This study investigated the effects of penehyclidine hydrochloride on rat spinal nerve ligation injury-induced neuropathic pain with behavioral, morphological, and molecular biological methods in animals.
RESULTS
The results indicated that penehyclidine hydrochloride could attenuate spinal nerve ligation-induced neuropathic pain without any motor impairment and had no effect on sham-operated animals after repeated intraperitoneal administration. Intraperitoneal penehyclidine hydrochloride could suppress spinal nerve ligation-induced ipsilateral spinal dorsal horn microglial activation with downregulation of OX42 expression. Moreover, intraperitoneal penehyclidine hydrochloride inhibited spinal nerve ligation-induced spinal p-p38 mitogen-activated protein kinase expression, which was specially colocalized with the spinal dorsal horn microglia. Furthermore, intraperitoneal penehyclidine hydrochloride could depress spinal neuroinflammation by suppressing spinal nerve ligation-induced interleukin (IL)-1β over-expression.
CONCLUSION
These results indicated that the anti-allodynic effects of penehyclidine hydrochloride on spinal nerve ligation-induced neuropathic pain did not rely on motor impairment. Inhibiting spinal microglial p-p38/IL-1β pathway activation might contribute to the anti-allodynic effect of penehyclidine hydrochloride on nerve injury-induced neuropathic pain.
Topics: Animals; Injections, Intraperitoneal; Interleukin-1beta; Ligation; Male; Microglia; Motor Activity; Neuralgia; Peripheral Nerve Injuries; Phosphorylation; Quinuclidines; Rats, Sprague-Dawley; Rotarod Performance Test; Signal Transduction; Spinal Cord Dorsal Horn; Spinal Nerves; p38 Mitogen-Activated Protein Kinases
PubMed: 31149893
DOI: 10.1177/1744806919858260 -
Pain Mar 2014Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral...
Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral nerve regeneration, and functional recovery after partial lesions distal to the dorsal root ganglion (DRG) remains unknown. In the present investigation, male Sprague Dawley rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. Starting the day of injury, animals received intermittent subcutaneous artemin or vehicle across 2weeks. Sensory thresholds to tactile or thermal stimuli were monitored for 6weeks after injury. Immunohistochemical analyses of the DRG and nerve regeneration were performed at the 6-week time point. Artemin transiently reversed tactile and thermal hypersensitivity after axotomy, ligation, or crush injury. Thermal and tactile hypersensitivity reemerged within 1week of treatment termination. However, artemin-treated rats with nerve crush, but not axotomy or ligation, subsequently showed gradual return of sensory thresholds to preinjury baseline levels by 6weeks after injury. Artemin normalized labeling for NF200, IB4, and CGRP in nerve fibers distal to the crush injury, suggesting persistent normalization of nerve crush-induced neurochemical changes. Sciatic and intradermal administration of dextran or cholera toxin B distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting regeneration functional restoration of nonmyelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase 3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring preinjury sensory thresholds.
Topics: Animals; Male; Nerve Growth Factor; Nerve Regeneration; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Nerves
PubMed: 24269493
DOI: 10.1016/j.pain.2013.11.007 -
BMC Developmental Biology May 2009The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the...
BACKGROUND
The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo.
RESULTS
Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity.
CONCLUSION
We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.
Topics: Animals; Body Patterning; Cell Differentiation; Embryo, Mammalian; Gene Expression Regulation, Developmental; In Situ Hybridization; Mice; Neurogenesis; RNA; Somites; Spinal Nerves
PubMed: 19463158
DOI: 10.1186/1471-213X-9-30 -
The Journal of Neuroscience : the... Mar 2006Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by...
A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance.
Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (<12 h) but transient activation of JNK in the L5 (injured) but not L4 (intact) DRG. JNK activation in the DRG was mainly found in small-sized C-fiber neurons. Infusion of D-JNKI-1 into the L5 DRG prevented but did not reverse SNL-induced mechanical allodynia. Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.
Topics: Animals; Astrocytes; Enzyme Activation; Ganglia, Spinal; Hyperalgesia; MAP Kinase Kinase 4; Male; Neuralgia; Neurons, Afferent; Peptides; Rats; Rats, Sprague-Dawley; Spinal Nerves
PubMed: 16571763
DOI: 10.1523/JNEUROSCI.5290-05.2006