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Pain Physician May 2017Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits...
BACKGROUND
Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits structural similarities to tricyclic antidepressants but has distinct neurochemical properties.
OBJECTIVE
Here we examined the effects of intraperitoneal (i.p.) tianeptine on allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice.
STUDY DESIGN
A randomized, experimental trial.
SETTING
Laboratory animal study.
METHODS
Spinal nerve-ligated neuropathy was induced in a Chung model made by ligating the L5 spinal nerve. Chemotherapy-induced neuropathy was induced by injecting vincristine (0.1 mg/kg/day; i.p.) on the following schedule: 5 days on, 2 days off, for14 days. Tianeptine (10, 30, and 50 mg/kg) and saline were administered, respectively, to both groups of neuropathic mice (n = 5 for each group). We evaluated mechanical allodynia using von Frey hairs prior to drug injections and at 30, 60, 90, 120, 180, and 240 minutes, and 24 hours after injections. We also measured the changes in activate transcription factor 3 (ATF3) level in the dorsal root ganglion (DRG) in each group in order to understand the analgesic mechanism of tianeptine.
RESULTS
Both spinal nerve-ligated and chemotherapy-induced neuropathic mice showed prominent allodynia. The control group showed no differences in mechanically induced allodynia compared to the experimental groups. For the tianeptine groups, paw-withdrawal thresholds in response to mechanical stimuli were significantly lower than the pre-administration values and values from the control group (P < 0.05). The increase in DRG ATF3 in neuropathic mice was reduced by tianeptine (P < 0.05).
LIMITATIONS
Less is known about the transcription factors that affect inflammation signaling.
CONCLUSIONS
Tianeptine administered i.p. reduces mechanical allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice models. These effects were confirmed by attenuation of previously increased DRG ATF3.
Topics: Activating Transcription Factor 3; Analgesics; Animals; Disease Models, Animal; Ganglia, Spinal; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Neuralgia; Rats, Sprague-Dawley; Spinal Nerves; Thiazepines; Vincristine
PubMed: 28535568
DOI: No ID Found -
Orthopaedics & Traumatology, Surgery &... Apr 2023Previous studies reported that spinal nerve edema on magnetic resonance myelography (MRM) and leg pain at rest were specifically observed in symptomatic lumbar foraminal...
BACKGROUND
Previous studies reported that spinal nerve edema on magnetic resonance myelography (MRM) and leg pain at rest were specifically observed in symptomatic lumbar foraminal stenosis patients. However, the correlation between leg pain at rest and spinal nerve edema in symptomatic foraminal stenosis has not been reported.
HYPOTHESIS
The purpose of this prospective study is to reveal a correlation between leg pain at rest and spinal nerve edema focusing on the pathophysiology of symptomatic foraminal stenosis.
PATIENTS AND METHODS
Clinical findings and MRM findings were surveyed among 30 patients with symptomatic foraminal stenosis diagnosed by MR imaging (MRI) and selective nerve root block. Comparisons of patient characteristics and clinical findings between the prevalence and absence groups of spinal nerve edema on MRM were analyzed. A correlation between the visual analogue scale (VAS) for leg pain at rest and the spinal edema ratio calculated as maximum intensity value of the affected spinal nerve/maximum intensity value of the asymptomatic side from region of interest (ROI) made on MRM was evaluated.
RESULTS
Twenty symptomatic foraminal stenosis cases (67%) showed the affected spinal nerve edema on MRM. The prevalence and VAS of leg pain at rest were significantly higher in the presence of spinal nerve edema group (95% and 67.0±36.4, respectively). The correlation coefficient between the VAS for leg pain at rest (53.0±33.6) and the spinal nerve edema ratio (1.3±0.3) was 0.647 (p<0.01).
DISCUSSION
Our study revealed the substantial correlation found between the spinal nerve edema ratio on MRM and the VAS for leg pain at rest in symptomatic foraminal stenosis. The correlation between spinal nerve edema and leg pain at rest has potential to clarify the pathology of symptomatic foraminal stenosis.
LEVEL OF EVIDENCE
IV.
Topics: Humans; Constriction, Pathologic; Spinal Stenosis; Prospective Studies; Leg; Lumbar Vertebrae; Spinal Nerves; Pain; Magnetic Resonance Imaging; Edema
PubMed: 34666199
DOI: 10.1016/j.otsr.2021.103119 -
Anesthesiology Sep 2018WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The...
WHAT WE ALREADY KNOW ABOUT THIS TOPIC
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The authors hypothesized that recovery in rats after surgery could be reversed by antagonism of spinal oxytocin or vasopressin receptors, that there may be a sex difference, and that spinal oxytocin innervation could change after surgery.
METHODS
Male and female rats underwent partial spinal nerve ligation surgery. Effects of nonselective and selective oxytocin and vasopressin 1A receptor antagonists on mechanical hypersensitivity during partial recovery were assessed (n = 8 to 14/group). Oxytocin immunoreactivity in the dorsal horn of the spinal cord (n = 7 to 8/group) and messenger RNA (mRNA) expression for oxytocin-binding receptors in dorsal root ganglia and spinal cord (n = 8/group) were measured.
RESULTS
Intrathecal injection of oxytocin and vasopressin receptor antagonists were similarly effective at reducing withdrawal threshold (in all experiments from 22 [19, 26] median [first quartile, third quartile]) g to 8.3 [6.4, 12] g after injection) in both sexes, while having no or minimal effects in animals without surgery. Oxytocin fiber immunoreactivity was 3- to 5-fold greater in lumbar than other regions of the spinal cord and was increased more than 2-fold in lumbar cord ipsilateral to surgery. Injury was also associated with a 6.5-fold increase in oxytocin receptor and a 2-fold increase in vasopressin 1A receptor messenger RNA expression in the L4 dorsal root ganglion ipsilateral to surgery.
CONCLUSIONS
These findings suggest that the capacity for oxytocin signaling in the spinal cord increases after surgery and that spinal oxytocin signaling plays ongoing roles in both sexes in recovery from mechanical hypersensitivity after surgery with known nerve injury.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Female; Hyperalgesia; Injections, Spinal; Ligation; Male; Oxytocin; Pain, Postoperative; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Recovery of Function; Signal Transduction; Spinal Nerves
PubMed: 29912007
DOI: 10.1097/ALN.0000000000002290 -
Pain Medicine (Malden, Mass.) Aug 2020Peripheral nerve stimulation provides targeted stimulation and pain relief within a specific nerve distribution. This technical case report provides a method to perform...
OBJECTIVE
Peripheral nerve stimulation provides targeted stimulation and pain relief within a specific nerve distribution. This technical case report provides a method to perform selective nerve root stimulation of thoracic and lumbar spinal nerves using ultrasonography.
METHODS
Ultrasound-guided peripheral nerve stimulation of thoracic and lumbar spinal nerves allows better visualization of soft tissue anatomy and planning of needle trajectory.
CONCLUSIONS
Ultrasound-guided peripheral nerve stimulation procedures may provide a safer method for neurostimulation lead placement when compared with fluoroscopic-guided techniques.
Topics: Humans; Peripheral Nerves; Spinal Nerves; Transcutaneous Electric Nerve Stimulation; Ultrasonography; Ultrasonography, Interventional
PubMed: 32804223
DOI: 10.1093/pm/pnaa166 -
Orthopaedic Surgery Feb 2022To achieve the anatomical evaluation of spinal nerve and cervical intervertebral foramina in anterior controllable antedisplacement and fusion (ACAF) surgery, a novel...
OBJECTIVE
To achieve the anatomical evaluation of spinal nerve and cervical intervertebral foramina in anterior controllable antedisplacement and fusion (ACAF) surgery, a novel surgical technique with the wider decompression, through a cadaveric and radiologic study.
METHODS
Radiographic data of consecutive 47 patients (21 by ACAF and 26 by anterior cervical corpectomy and fusion [ACCF]) who have accepted surgery for treatment of cervical ossification of the posterior longitudinal ligament(OPLL) and stenosis from March 2017 to March 2018 were retrospectively reviewed and compared between an ACAF group and ACCF group. Three postoperative radiographic parameters were evaluated: the decompression width and the satisfaction rate of decompression at the entrance zone of intervertebral foramina on computed tomography (CT), and the transverse diameter of spinal cord in the decompression levels on magnetic resonance imaging (MRI). In the anatomic study, three fresh cadaveric spines (death within 3 months) undergoing ACAF surgery were also studied. Four anatomic parameters were evaluated: the width of groove, the distance between the bilateral origins of ventral rootlets, the length of ventral rootlet from their origin to the intervertebral foramina, the descending angle of ventral rootlet.
RESULTS
The groove created in ACAF surgery included the bilateral origins of ventral rootlets. The rootlets tended to be vertical from the rostral to the caudal direction as their takeoff points from the central thecal sac became higher and farther away from their corresponding intervertebral foramina gradually. No differences were identified between left and right in terms of the length of ventral rootlet from the origin to the intervertebral foramina and the descending angle of ventral rootlet. The decompression width was significantly greater in ACAF group (19.2 ± 1.2 vs 14.7 ± 1.2, 21.3 ± 2.2 vs 15.4 ± 0.9, 21.5 ± 2.1 vs 15.7 ± 1.0, 21.9 ± 1.6 vs 15.9 ± 0.8, from C to C ). The satisfactory rate of decompression at the entrance zone of intervertebral foramina tended to be better in the left side in ACAF group (significant differences were identified in the left side at C , C , C level, and in the right side at C level when compared with ACCF). And decompression width was significantly greater than the transverse diameter of spinal cord in ACAF group. Comparatively, there existed no significant difference in the ACCF group besides the C level.
CONCLUSION
ACAF can decompress the entrance zone of intervertebral foramina effectively and its decompression width includes the origins and massive running part of bilateral ventral rootlets. Due to its wider decompression range, ACAF can be used as a revision strategy for the patients with failed ACCF.
Topics: Cadaver; Cervical Vertebrae; Decompression, Surgical; Humans; Ossification of Posterior Longitudinal Ligament; Retrospective Studies; Spinal Fusion; Spinal Nerves; Treatment Outcome
PubMed: 34935286
DOI: 10.1111/os.13181 -
Molecular Pain Jul 2015Calcium-activated chloride channels (CaCCs) activation induces membrane depolarization by increasing chloride efflux in primary sensory neurons that can facilitate...
BACKGROUND
Calcium-activated chloride channels (CaCCs) activation induces membrane depolarization by increasing chloride efflux in primary sensory neurons that can facilitate action potential generation. Previous studies suggest that CaCCs family members bestrophin-1 and anoctamin-1 are involved in inflammatory pain. However, their role in neuropathic pain is unclear. In this investigation we assessed the involvement of these CaCCs family members in rats subjected to the L5/L6 spinal nerve ligation. In addition, anoctamin-1 and bestrophin-1 mRNA and protein expression in dorsal root ganglion (DRG) and spinal cord was also determined in the presence and absence of selective inhibitors.
RESULTS
L5/L6 spinal nerve ligation induced mechanical tactile allodynia. Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose-dependently reduced tactile allodynia. Intrathecal administration of selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) also dose-dependently diminished tactile allodynia and thermal hyperalgesia. Anoctamin-1 and bestrophin-1 mRNA and protein were expressed in the dorsal spinal cord and DRG of naïve, sham and neuropathic rats. L5/L6 spinal nerve ligation rose mRNA and protein expression of anoctamin-1, but not bestrophin-1, in the dorsal spinal cord and DRG from day 1 to day 14 after nerve ligation. In addition, repeated administration of CaCCs inhibitors (T16Ainh-A01, CaCCinh-A01 or NFA) or anti-anoctamin-1 antibody prevented spinal nerve ligation-induced rises in anoctamin-1 mRNA and protein expression. Following spinal nerve ligation, the compound action potential generation of putative C fibers increased while selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) attenuated such increase.
CONCLUSIONS
There is functional anoctamin-1 and bestrophin-1 expression in rats at sites related to nociceptive processing. Blockade of these CaCCs suppresses compound action potential generation in putative C fibers and lessens established tactile allodynia. As CaCCs activity contributes to neuropathic pain maintenance, selective inhibition of their activity may function as a tool to generate analgesia in nerve injury pain states.
Topics: Animals; Anoctamin-1; Bestrophins; Chloride Channels; Female; Hyperalgesia; Injections, Spinal; Ligation; Motor Activity; Neural Conduction; Neuralgia; RNA, Messenger; Rats, Wistar; Spinal Cord; Spinal Nerves
PubMed: 26130088
DOI: 10.1186/s12990-015-0042-1 -
Anatomical Record (Hoboken, N.J. : 2007) Apr 2021A peridural membranous layer exists between the bony wall of the spinal canal and the dura mater, but reports on the anatomy of this structure have been inconsistent....
A peridural membranous layer exists between the bony wall of the spinal canal and the dura mater, but reports on the anatomy of this structure have been inconsistent. The objective of this study is to give a precise description of the peridural membrane (PDM) and to define it unambiguously as a distinct and unique anatomical entity. Thirty-four cadaveric sections of human thoraco-lumbar spines were dissected. On gross examination, the PDM appears as a smooth hollow tube that covers the bony wall of the spinal canal. An evagination of this tube into the neural foramen contains the exiting spinal nerve. The entire epidural venous plexus, including its extension into the neural foramina, is contained in the body of the PDM. Histological examination of the PDM shows a variable distribution of veins arteries, lymphatics, and nerves embedded in a continuous sheath of fibrous, areolar, and adipose tissue. The posterior longitudinal ligament may be considered a dense condensation of fibrous tissue within the membrane. Thus, the PDM is a unique, continuous, and complete anatomical structure. In the spinal canal, the PDM is adjacent to the periosteum. In the neural foramen, suprapedicular PDM and pedicular periosteum separate anatomically to form a suprapedicular compartment, bounded anteriorly by the intervertebral disc and posteriorly by the facet joint. Trauma or degeneration of the disc or facet joint may lead to inflammation and pain sensitization of PDM. This protective mechanism may be of considerable importance for the functioning of the spine under conditions of strain.
Topics: Cadaver; Dura Mater; Epidural Space; Humans; Spinal Nerves; Spine
PubMed: 32562360
DOI: 10.1002/ar.24476 -
Neuroscience Sep 2021Voltage-gated Ca (Ca) channels regulate multiple cell processes, including neurotransmitter release, and have been associated with several pathological conditions, such...
L5-6 Spinal Nerve Ligation-induced Neuropathy Changes the Location and Function of Ca Channels and Cdk5 and Affects the Compound Action Potential in Adjacent Intact L4 Afferent Fibers.
Voltage-gated Ca (Ca) channels regulate multiple cell processes, including neurotransmitter release, and have been associated with several pathological conditions, such as neuropathic pain. Cdk5, a neuron-specific kinase, may phosphorylate Ca channels, altering their functional expression. During peripheral nerve injury, upregulation of Ca channels and Cdk5 in the dorsal root ganglia (DRG) and the spinal cord, has been correlated with allodynia. We recently reported an increase in the amplitude of the C component of the compound action potential (cAP) of afferent fibers in animals with allodynia induced by L5-6 spinal nerve ligation (SNL), recorded in the corresponding dorsal roots. This was related to an increase in T-type (Ca3.2) channels generated by Cdk5-mediated phosphorylation. Here, we show that Ca channel functional expression is also altered in the L4 adjacent intact afferent fibers in rats with allodynia induced by L5-6 SNL. Western blot analysis showed that both Cdk5 and Ca3.2 total levels are not increased in the DRG L3-4, but their subcellular distribution changes by concentrating on the neuronal soma. Likewise, the Cdk5 inhibitor olomoucine affected the rapid and the slow C components of the cAP recorded in the dorsal roots. Patch-clamp recordings revealed an increase in T- and N-type currents recorded in the soma of acute isolated L3-4 sensory neurons after L5-6 SNL, which was prevented by olomoucine. These findings suggest changes in Ca channels location and function in L3-4 afferent fibers associated with Cdk5-mediated phosphorylation after L5-6 SNL, which may contribute to nerve injury-induced allodynia.
Topics: Action Potentials; Animals; Cyclin-Dependent Kinase 5; Ganglia, Spinal; Hyperalgesia; Neuralgia; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Spinal Nerves
PubMed: 34303780
DOI: 10.1016/j.neuroscience.2021.07.013 -
Journal of Korean Medical Science Apr 2016Occipital neuralgia is defined by the International Headache Society as paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser occipital nerve.... (Review)
Review
Occipital neuralgia is defined by the International Headache Society as paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser occipital nerve. Various treatment methods exist, from medical treatment to open surgical procedures. Local injection with corticosteroid can improve symptoms, though generally only temporarily. More invasive procedures can be considered for cases that do not respond adequately to medical therapies or repeated injections. Radiofrequency lesioning of the greater occipital nerve can relieve symptoms, but there is a tendency for the pain to recur during follow-up. There also remains a substantial group of intractable patients that do not benefit from local injections and conventional procedures. Moreover, treatment of occipital neuralgia is sometimes challenging. More invasive procedures, such as C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, neurectomy, and neurolysis with or without sectioning of the inferior oblique muscle, are now rarely performed for medically refractory patients. Recently, a few reports have described positive results following peripheral nerve stimulation of the greater or lesser occipital nerve. Although this procedure is less invasive, the significance of the results is hampered by the small sample size and the lack of long-term data. Clinicians should always remember that destructive procedures carry grave risks: once an anatomic structure is destroyed, it cannot be easily recovered, if at all, and with any destructive procedure there is always the risk of the development of painful neuroma or causalgia, conditions that may be even harder to control than the original complaint.
Topics: Anesthetics; Botulinum Toxins; Electric Stimulation; Humans; Magnetic Resonance Imaging; Nerve Block; Neuralgia; Spinal Nerves; Steroids
PubMed: 27051229
DOI: 10.3346/jkms.2016.31.4.479 -
Journal of Neurochemistry Aug 2021Emerging evidence indicates the early growth response 1 (Egr1) plays an important role in the pathogenesis of chronic pain. However, the regulation of Egr1 expression in...
MicroRNA-124-3p attenuates the development of nerve injury-induced neuropathic pain by targeting early growth response 1 in the dorsal root ganglia and spinal dorsal horn.
Emerging evidence indicates the early growth response 1 (Egr1) plays an important role in the pathogenesis of chronic pain. However, the regulation of Egr1 expression in the DRG and spinal cord in neuropathic pain remains unclear. In the current study, the neuropathic pain was conducted by lumber 5 spinal nerve ligation (SNL) in rats. The role of miR-124-3p in Egr1 expression was examined. Our results showed that the SNL led to a significant increase in the expression of Egr1 mRNA and protein in the DRG and dorsal horn. This increased expression of Egr1 correlated with a reduction of miR-124-3p in the same region. Prior i.t. injection of Egr1 decoy AYX1 inhibited the expression of Egr1 and attenuated the neuropathic pain-like hypersensitivity following SNL. The dual-luciferase reporter assay revealed the luciferase activity of the Egr1 3'-UTR plasmid was inhibited by the miR-124-3p agomir. But this inhibition was completely reversed in the mutant 3'-UTR Egr1 group. In vivo, the SNL-induced behavioral signs of neuropathic pain and the increases in Egr1 mRNA and protein in the DRG and dorsal horn were prevented by prior to i.t. injection of miR-124-3p agomir. While, i.t. injection of miR-124-3p antagomir in naïve rats resulted in mechanical allodynia and thermal hyperalgesia and an overexpression of Egr1 in the DRG and dorsal horn. Together, our results suggest that the miR-124-3p-regulated Egr1 expression in the DRG and dorsal horn contributes to the development of neuropathic pain. Targeting miR-124-3p might be a promising therapeutic strategy in the treatment of chronic pain.
Topics: 3' Untranslated Regions; Animals; Behavior, Animal; Early Growth Response Protein 1; Ganglia, Spinal; Gene Transfer Techniques; Genetic Therapy; Hyperalgesia; Ligation; Male; MicroRNAs; Neuralgia; Peripheral Nerve Injuries; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Spinal Nerves
PubMed: 34008206
DOI: 10.1111/jnc.15433