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Indian Journal of Pharmacology 2023The goal of the research is to investigate the protocatechuic acid (PCA) potential action, a phenolic acid derivative, on pain induced by neuropathy and to determine its...
OBJECTIVES
The goal of the research is to investigate the protocatechuic acid (PCA) potential action, a phenolic acid derivative, on pain induced by neuropathy and to determine its efficacy on activation of K type channels and A receptors.
MATERIALS AND METHODS
Neuropathic pain by cause of sciatic nerve damage was induced in Sprague-Dawley rats. Anti-allodynic and anti-hyperalgesic effects were evaluated with von Frey apparatus and Hargreave's plantar test apparatus, respectively. The effects of PCA at the doses of 75, 150 and 300 mg/kg, carbamazepine at the doses of 50 and 100 mg/kg, combination of low effective doses of PCA and carbamazepine were tested. Pretreatments 3 μg/kg DPCPX as adenosine A receptor antagonist and 60.7 nmol glibenclamide as K channel blocker were applied for mechanistic studies.
RESULTS
PCA showed anti-allodynic and anti-hyperalgesic effects without impairing locomotor activity. In addition, the combination treatment was found to be more effective than the separate individual treatments of drugs. K channel activation related with A receptor stimulation makes a significant contribution to the anti-allodynia and anti-hyperalgesia induced by PCA.
CONCLUSIONS
It can be said that PCA has similar effects with carbamazepine, which is used in clinical practice, and that PCA can take place as an adjuvant drug in neuropathic pain with the combination group. In addition, it is seen that the undesirable effects that drugs can cause alone can be avoided and a more effective treatment potential can be created with multiple mechanisms.
Topics: Rats; Animals; Rats, Sprague-Dawley; Neuralgia; Hyperalgesia; Carbamazepine; Adenosine Triphosphate
PubMed: 37929410
DOI: 10.4103/ijp.ijp_364_21 -
Physiological Research Dec 2023Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine...
Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain.
Topics: Humans; Rats; Animals; Hyperalgesia; Methylphenidate; Rats, Wistar; Disease Models, Animal; Neuralgia
PubMed: 38165759
DOI: 10.33549/physiolres.935215 -
JBJS Essential Surgical Techniques 2023Painful neuromas of the foot and ankle frequently pose a treatment dilemma because of persistent pain or recurrence after resection. Primary surgical treatment of...
BACKGROUND
Painful neuromas of the foot and ankle frequently pose a treatment dilemma because of persistent pain or recurrence after resection. Primary surgical treatment of painful neuromas includes simple excision with retraction of the residual nerve ending to a less vulnerable location. The use of a collagen conduit for recurrent neuromas is advantageous, particularly in areas with minimal soft-tissue coverage options, and is a technique that has shown 85% patient satisfaction regarding surgical outcomes. Additionally, the use of a collagen conduit limits the need for deep soft-tissue dissection and reduces the morbidity typically associated with nerve burial.
DESCRIPTION
Specific steps include appropriate physical examination, preoperative planning, and supine patient positioning. The patient is placed supine with a lower-extremity bolster under the ipsilateral extremity in order to allow improved visualization of the plantar surface of the foot. A nonsterile tourniquet is placed on the thigh. The incision site is marked out, and a longitudinal plantar incision is made until proximal healthy nerve is identified-typically approximately 1 to 2 cm, but the incision can be extended up to 6 cm. The incision is made between the metatarsals, with blunt dissection carried down to the neuroma. The neuroma is sharply excised distally through healthy nerve, and a whip stitch is placed to facilitate the collagen conduit placement. The collagen conduit is passed dorsally into the intermetatarsal space and secured to the dorsal fascia of the foot. The wound is closed with 3-0 nylon horizontal mattress sutures. Postoperatively, a soft dressing is applied to the operative extremity, and patients are advised to be non-weight-bearing for two weeks. At two weeks, patients begin partial weight-bearing with use of a boot, and physical therapy is initiated. No antibiotics are necessary, and 300 mg of gabapentin is prescribed and tapered off by the six-week follow-up visit. Follow-ups are conducted at 2, 6, 12, 24, and fifty-two weeks. It is necessary to monitor for signs and symptoms of infection, surgical complications, and neuroma recurrence during follow-up appointments.
ALTERNATIVES
Simple excision of the neuroma with proximal burial into muscle or bone is a common surgical technique. However, inadequate resection of the nerve or poor surgical technique can lead to recurrent neuromas. For neuromas not responding to simple excision, other techniques have been utilized, including cauterization, chemical agents, nerve capping, and muscle or bone burial. The results of these techniques have varied, and none has gained clinical superiority over the other.
RATIONALE
A study analyzing the use of collagen conduits for painful neuromas of the foot and ankle has shown this technique to be a safe and successful alternative to the previously discussed methods of resection. That study by Gould et al. found that 85% of patients had a substantial reduction in pain, with mean visual analog scale (VAS) pain scores reducing from 8 to 10 preoperatively to 0 to 4 postoperatively. Moreover, alternative biological conduits, such as the greater saphenous vein, have proven to be costly in time and resources, as this structure is often utilized in cardiovascular bypass surgery and its harvest conveys a risk of iatrogenic nerve injury to the patient.Numerous studies focusing on excision of recurrent Morton neuromas via a plantar approach have found variable success rates. Of the patients surveyed in those studies, 75% reported substantial pain improvement. However, <50% of these queried patients reported complete pain relief. Studies analyzing the dorsal approach for revision Morton neuroma excision found similar success rates. Approximately 78% of patients reported good or excellent postoperative outcomes, and significant improvements were observed in patient postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores for pain interference, intensity, and global physical health. One study comparing outcomes following plantar versus dorsal approaches for recurrent Morton neuroma found no significant difference in postoperative patient outcomes. That study suggested that surgeons utilize the approach with which they are most comfortable. Gould et al. reported an 85% success rate with collagen conduit, which was similar to if not slightly improved compared with the other prior studies. The utilization of a collagen conduit technique thus offers comparable patient outcomes for patients with difficult neuromas.
EXPECTED OUTCOMES
Recurrent neuroma resection with the use of a collagen conduit has proven to provide satisfactory patient outcomes regarding pain and neuritis symptoms. The goal of any neuroma resection is to greatly diminish or entirely eliminate nerve pain. Based on the available evidence, there has been no proven clinical superiority of any particular technique over the others. However, in the present example case, the location of the patient's neuroma in this video makes it 85% likely that the patient will report satisfactory outcomes and 50% likely that the patient will be entirely symptom-free. At two weeks postoperatively, the patient reported well controlled pain, absence of burning or tingling sensation, full range of movement in the foot, and intact sensation throughout all major nerve distributions, including the saphenous; superficial peroneal nerve; deep peroneal nerve; and sural, medial, and lateral plantar nerves. However, sensation is absent distal to the site of a neuroma resection.
IMPORTANT TIPS
Careful preoperative planting is of utmost importance.Ruling out other potential pathologies is necessary to ensure proper outcomes.Meticulous dissection should be carried out, with delicate handling of the proximal nerve ending.Excision of the nerve should be done sharply through the healthy portion of the nerve.Appropriate sizing of the nerve conduit (with a commercially available industry sizer) should be performed.The nerve conduit should be passed dorsally and secured to the dorsal fascia without any tension.
ACRONYMS AND ABBREVIATIONS
MRI = magnetic resonance imagingUS = ultrasoundVAS = visual analog scale.
PubMed: 38357467
DOI: 10.2106/JBJS.ST.22.00065 -
Journal of Orthopaedic Surgery and... Mar 2024Isolated gastrocnemius contracture has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis,...
BACKGROUND
Isolated gastrocnemius contracture has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flatfoot, and metatarsalgia. Although many techniques are available for gastrocnemius recession, potential anesthetic, cosmetic, and wound-related complications can lead to patient dissatisfaction. Open and endoscopic recession techniques usually require epidural or general anesthesia, exsanguination of the lower extremities and stitches and can damage the sural nerve, which is not under the complete control of the surgeon at all stages of the procedure. The purpose of this study is to evaluate the clinical results of a surgical technique for gastrocnemius lengthening with a needle, as previously described in cadaver specimens.
METHODS AND RESULTS
We performed a prospective study of ultrasound-guided gastrocnemius tendon lengthening in level II using a needle in 24 cases (19 patients) of gastrocnemius contracture. The study population comprised 12 males and 7 females. Mean age was 41 years (18-64). All but 5 recessions were bilateral and occurred simultaneously. The indication for the procedure was gastrocnemius contracture; although the patients also presented other conditions such as non-insertional Achilles tendinopathy in 6 patients (2 were bilateral), insertional Achilles calcifying enthesitis in 4 (1 was bilateral), metatarsalgia in 4, flexible flat foot in 1 and plantar fasciitis in 5 (2 were bilateral). The inclusion criteria were the failure of a previous conservative protocol, that the Silfverskiöld test was positive, and that the pathology suffered by the patient was within the indications for surgical lengthening of the patients and were described in the scientific literature. The exclusion criteria were that the inclusion criteria were not met, and patients with surgical risk ASA 3 or more and children. In these patients, although possible, it is preferable to perform the procedure in the operating room with monitoring, as well as in children since they could be agitated during the procedure at the office. We used the beveled tip of an Abbocath needle as a surgical scalpel. All patients underwent recession of the gastrocnemius tendon, as in an incomplete Strayer release. We evaluated pre- and postoperative dorsiflexion, outcomes, and procedural pain (based on a visual analog scale and the American Orthopedic Foot and Ankle Society scores), as well as potential complications. No damage was done to the sural bundle.
RESULTS
Ankle dorsiflexion increased on average by 17.89°. The average postoperative visual analog score for pain before surgery was 5.78, 5.53 in the first week, 1.89 at 1 month, and 0.26 at 3 months, decreasing to 0.11 at 9 months. The mean postoperative American Orthopedic Foot and Ankle Society Ankle-Hindfoot score the average was 50.52 before surgery, 43.42 at 1 week, 72.37 at 1 month, 87.37 at 3 months, and 90.79 at 9 months.
CONCLUSION
Ultrasound-guided needle lengthening of the gastrocnemius tendon is a novel, safe, and effective technique that enables the surgeon to check all the structures clearly, thus minimizing the risk of neurovascular damage. The results are encouraging, and the advantages of this approach include absence of a wound and no need for stitches. Recovery is fast and relatively painless. A specific advantage of ultrasound-guided needle lengthening of the gastrocnemius tendon is the fact that it can be performed in a specialist's office, with a very basic instrument set and local anesthesia, thus reducing expenses.
Topics: Adult; Male; Female; Child; Humans; Achilles Tendon; Prospective Studies; Fasciitis, Plantar; Tendinopathy; Muscle, Skeletal; Contracture; Ultrasonography, Interventional; Metatarsalgia
PubMed: 38532430
DOI: 10.1186/s13018-024-04685-0 -
Cureus Sep 2023Guillain-Barré syndrome (GBS) is the most prevalent form of autoimmune-related acute demyelinating polyneuropathy that affects people of any age group. Its global...
Guillain-Barré syndrome (GBS) is the most prevalent form of autoimmune-related acute demyelinating polyneuropathy that affects people of any age group. Its global prevalence is 1.9 per 100,000 people. Acute or subacute symmetrical motor and sensory neuropathy involving several peripheral nerves is referred to as GBS. It typically occurs after an infection caused by a virus, but infrequently with surgery or vaccination. There are different variants of GBS, like acute sensory axonal neuropathy, acute motor axonal neuropathy, and Miller-Fisher syndrome. Motor paralysis that affects distal muscles more than proximal muscles and is more pronounced and symmetrical may be a presenting symptom of GBS. Over the course of several days, it starts in the legs and progresses to the arms, face, and eyes. Reflexes may be missing, bifacial weakness may be present, severe cases result in respiratory paralysis, and autonomic abnormalities may be rare. Patients with GBS exhibit anti-ganglioside antibodies that seem to react with antigens found in some previous infectious pathogens' lipopolysaccharides. These antibodies target gangliosides, like GM1, which are dispersed within the myelin of the peripheral nervous system. There are three phases: acute, plateau, and recovery. Only plasmapheresis and intravenous immunoglobulin have shown effective recovery. A 24-year-old male presented with weakness of the bilateral lower limb associated with fever and breathlessness. The range of motion of hip flexion was reduced to 45 degrees, and muscle power was also reduced. For hip flexors, it was 3/5; for knee flexors and extensors, it was 4/5; and for ankle plantar flexors and dorsiflexors, it was 2/5. Investigations like a complete blood count (CBC), cerebrospinal fluid (CSF) examination, and nerve conduction velocity (NCV) were done. Post-diagnosis, the patient received an intravenous immunoglobulin (IVIG) dose; the same was managed by neurophysiotherapy, and after treatment, the patient was functionally independent. According to the findings of our study, neurorehabilitation resulted in favorable outcomes, shortened the length of the hospital stay, and enabled him to return to his desk job.
PubMed: 37842383
DOI: 10.7759/cureus.45101 -
Journal of Neurosciences in Rural... 2023Suprasacral spinal cord lesions are prone to have neurogenic detrusor overactivity leading to urinary incontinence. Current medical management has known side-effects and...
Neuromodulation of spinal reflex pathway for the treatment of detrusor overactivity by medial plantar nerve stimulation at surface of sole of foot in patients with spinal cord injury.
OBJECTIVES
Suprasacral spinal cord lesions are prone to have neurogenic detrusor overactivity leading to urinary incontinence. Current medical management has known side-effects and often surgical managements are irreversible. Electrical stimulation to modulate spinal reflex pathway having same nerve root as urinary bladder is reported in the literature. This study aimed to reduce detrusor overactivity in patients with spinal cord injury (SCI) using surface electrical stimulation of medial plantar nerve at the sole of foot.
MATERIALS AND METHODS
Twenty adults with SCI having episode of at least 1 leak/day due to detrusor overactivity as diagnosed by cystometrogram (CMG), were on clean intermittent catheterization and ankle jerk was present consented for the study. Participants were asked to maintain bladder diary a week before and during 2 weeks of treatment. CMG was done on day-0 and day-14. cmcUroModul@tor, an inhouse developed electrical stimulator was used for ½ h daily for period of 2 weeks. Patient satisfaction feedback questionnaire was taken on completion of treatment. CMG data were analyzed using Wilcoxon signed-ranked test while bladder diary was analyzed using binomial distribution. < 0.05 was considered as statistically significant. Institutional Review Board (IRB) and ethics committee of Christian Medical College, Vellore, approved the study (CMC/IRB/11061).
RESULTS
Statistical significant improvement in maximum detrusor pressure ( = 0.03) and cystometric capacity ( = 0.04) was observed. Of 20 subjects, 18 showed improvement in bladder diary.
CONCLUSION
Neuromodulation of medial plantar nerve at sole of foot by surface electrical stimulation is non-invasive, cost-effective, and alternative simple treatment modality for urinary incontinence due to detrusor overactivity.
PubMed: 37692814
DOI: 10.25259/JNRP_27_2023 -
International Neurourology Journal Dec 2023Lithotomy position has been widely used in the various urologic surgery. Occasionally sensory and motor problems of the lower extremities are occurred due to the...
PURPOSE
Lithotomy position has been widely used in the various urologic surgery. Occasionally sensory and motor problems of the lower extremities are occurred due to the lithotomy position and these deficits may be related with sciatic nerve injury (SNI). Inflammatory process is a factor to induce functional impairment after SNI. Therefore, we evaluated the role of adenosine A2A receptor agonists, polydeoxyribonucleotide (PDRN) showing anti-inflammatory effect on locomotor function following SNI in rats.
METHODS
Sciatic nerve was compressed with surgical clips for 1 minute after exposing of right sciatic nerve. After 3 days of SNI, PDRN (2, 4, and 8 mg/kg) was applied to the damaged area of sciatic nerve once daily for 10 days. Walking track analysis was conducted for locomotor function and plantar test was performed for thermal pain sensitivity. Level of cyclic adenosine-3´,5´-monophosphate (cAMP) were measured using enzyme-linked immunosorbent assay. Western blot analysis was performed for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cAMP response element binding protein (CREP), vascular endothelial growth factor (VEGF). Immunofluorescence for neurofilament was also conducted.
RESULTS
Locomotor function was decreased and thermal pain sensitivity was increased by SNI. SNI enhanced proinflammatory cytokines' production, such as TNF-α and IL-1β, while suppressed CREP phosphorylation and cAMP level. SNI also reduced the expression of VEGF and neurofilaments. However, treatment with PDRN inhibited proinflammatory cytokines' production and upregulated CREP phosphorylation and cAMP expression. PDRN also enhanced the expression of VEGF and neurofilaments. As a result, PDRN improved locomotor function and alleviated thermal hyperalgesia after SNI.
CONCLUSION
PDRN has shown potential to be used as an effective treatment for neuropathic pain.
PubMed: 38171324
DOI: 10.5213/inj.2326154.127 -
The Journal of Neuroscience : the... Apr 2024Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents...
Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aβ fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.
Topics: Female; Mice; Male; Animals; Peripheral Nerve Injuries; Nerve Regeneration; Skin; Neurogenesis; Neurons, Afferent
PubMed: 38471780
DOI: 10.1523/JNEUROSCI.1494-23.2024 -
Acta Neurochirurgica Dec 2023Polyethylene glycol is known to improve recovery following its use in repair of acute peripheral nerve injury. The duration till which PEG works remains a subject of...
PURPOSE
Polyethylene glycol is known to improve recovery following its use in repair of acute peripheral nerve injury. The duration till which PEG works remains a subject of intense research. We studied the effect of PEG with augmentation of 20Htz of electrical stimulation (ES) following neurorrhaphy at 48 h in a rodent sciatic nerve neurotmesis model.
METHOD
Twenty-four Sprague Dawley rats were divided into 4 groups. In group I, the sciatic nerve was transected and repaired immediately. In group II, PEG fusion was done additionally after acute repair. In group III, repair and PEG fusion were done at 48 h. In group IV, ES of 20Htz at 2 mA for 1 h was added to the steps followed for group III. Weekly assessment of sciatic functional index (SFI), pinprick, and cold allodynia tests were done at 3 weeks and euthanized. Sciatic nerve axonal count and muscle weight were done.
RESULTS
Groups II, III, and IV showed significantly better recovery of SFI (II: 70.10 ± 1.24/III: 84.00 ± 2.59/IV: 74.40 ± 1.71 vs I: 90.00 ± 1.38) (p < 0.001) and axonal counts (II: 4040 ± 270/III: 2121 ± 450/IV:2380 ± 158 vs I: 1024 ± 094) (p < 0.001) at 3 weeks. The experimental groups showed earlier recovery of sensation in comparison to the controls as demonstrated by pinprick and cold allodynia tests and improved muscle weights. Addition of electrical stimulation helped in better score with SFI (III: 84.00 ± 2.59 vs IV: 74.40 ± 1.71) (p < 0.001) and muscle weight (plantar flexors) (III: 0.49 ± 0.02 vs IV: 0.55 ± 0.01) (p < 0.001) in delayed repair and PEG fusions.
CONCLUSION
This study shows that PEG fusion of peripheral nerve repair in augmentation with ES results in better outcomes, and this benefit can be demonstrated up to a window period of 48 h after injury.
Topics: Rats; Animals; Rats, Sprague-Dawley; Polyethylene Glycols; Hyperalgesia; Disease Models, Animal; Sciatic Nerve; Trauma, Nervous System; Peripheral Nerve Injuries; Electric Stimulation; Nerve Regeneration; Recovery of Function
PubMed: 37907766
DOI: 10.1007/s00701-023-05854-6