Sural hypersensitivity after nerve transection depends on anatomical differences in the distal tibial nerve of mice and rats

Brakkee, EM; DeVinney, Erick; Eijkelkamp, Niels; Coert, J. Henk

doi:10.1016/j.aanat.2022.152038

Cited by 4 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tibial nerve injury model is well established and widely used to study neuropathic pain. Mice with TNI develop significant mechanical hypersensitivity from 1 week after surgery that persists for several weeks [ 24 ]. Briefly, after a mouse was anesthetized with ketamine/xylazine (87.7 mg/kg/12.3 mg/kg, i.p.…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain

et al. 2023

View full text Add to dashboard Cite

Clinical and animal studies have shown that acupuncture may benefit controlling neuropathic pain. However, the underlying molecular mechanisms are poorly understood. In a well-established mouse unilateral tibial nerve injury (TNI) model, we confirmed the efficacy of electroacupuncture (EA) in reducing mechanical allodynia and measured methylation and hydroxy-methylation levels in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC), two cortical regions critically involved in pain processing. TNI resulted in increased DNA methylation of both the contra- and ipsilateral S1, while EA only reduced contralateral S1 methylation. RNA sequencing of the S1 and ACC identified differentially expressed genes related to energy metabolism, inflammation, synapse function, and neural plasticity and repair. One week of daily EA decreased or increased the majority of up- or downregulated genes, respectively, in both cortical regions. Validations of two greatly regulated genes with immunofluorescent staining revealed an increased expression of gephyrin in the ipsilateral S1 after TNI was decreased by EA; while TNI-induced increases in Tomm20, a biomarker of mitochondria, in the contralateral ACC were further enhanced after EA. We concluded that neuropathic pain is associated with differential epigenetic regulations of gene expression in the ACC and S1 and that the analgesic effect of EA may involve regulating cortical gene expression.

show abstract

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In recent times, studies have indicated bene cial health and the ability to curb surgical complications and better performance of surgical procedures being linked to a proper understanding of the anatomical variations of the sciatic nerve (7,16,20,27,29,(33)(34)(35)(36). However, there is little Africa-speci c data on the pattern, morphometry, and anatomical variations of the sciatic nerve (33,37,38), and the current study is one of the few that have been done to examine the variations of the morphometric features, pattern, and bilateral and sex-related variability of the nerve in males and females (33,56), especially in the Ugandan context (30).…”

Section: Figure 4herementioning

confidence: 99%

“…Table 2here Table 3here Discussion Anatomical variations of the sciatic nerves are associated with important clinical roles (35,52,58), such as the causation and treatment of pathophysiologies like sciatica due to sciatic nerve compression (6, 18), piriformis syndrome (6, 20), injection-induced and post-injection damage to the sciatic nerve and paralysis (26, 27), and is also essential for clinicians and surgeons carrying out procedures involving the hip and sacroiliac joints such as the location of the main trunk of the sciatic nerve before its termination and successful popliteal sciatic nerve block (6, 7, 28), and so on. These conditions and procedures are highly dependent on the anatomical variations in the course and morphometric characteristics of the sciatic nerve knowledge of which is crucial (29,59,60).…”

Section: Figure 4herementioning

confidence: 99%

“…Variations of the Sciatic nerve in the population are important clinically since they are usually linked to nerve compression and entrapment syndromes such as sciatica (18, 19), piriformis syndrome (5,(20)(21)(22), accidental iatrogenic damage to the nerve during invasive procedures (23,24), injection-induced and post-injection damage to the sciatic nerve and paralysis following intragluteal intramuscular injection (2,(25)(26)(27). Also, the variations of the sciatic nerve anatomically make it di cult to precisely follow and locate its course contributing to high failure rates of some invasive procedures (28,29). One case in point is the high failure rate (21%) of popliteal sciatic nerve blocks in a Ugandan population which has been mainly attributed to the di culty in nding or identi cation of the main trunk of the nerve before its termination (30), and variations in the termination pattern of the nerve are of utmost importance during the administration of regional sciatic nerve block during surgeries below the genu (30).…”

mentioning

confidence: 99%

“…The exit nature of the sciatic nerve from the pelvis and its relation with the piriformis muscle (14,15,31,32), course and muscular branching patterns of the sciatic nerve in the thigh (16), level of terminal division of the nerve into the tibial and common peroneal nerves (happens in the popliteal fossa in most people) (17,29), show numerous anatomical variations that are of crucial clinical importance. Also of important clinical signi cance are the morphometric features and variations of the sciatic nerve that pertain to its dimensions (length, diameter, width) at different levels during its course in the gluteal and thigh regions (33,34).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Morphologic and morphometric bilateral analysis and sexual dimorphism in sciatic nerves of adults: an anatomic investigation of cadaveric specimens in Uganda with implications on sciatic nerve neuropathologies

Kegoye,

Ojewale,

Ezekiel

et al. 2023

Preprint

View full text Add to dashboard Cite

Background The Sciatic nerve (SN) depicts sex and side-associated dimorphic features that are of clinical relevancy. The study investigated the sex and side-related morphologic and morphometric variations of the nerve using cadavers. Methods A cross-sectional cadaveric study on 62 Ugandan cadavers were used. Continuous variables were reported using descriptive statistics and discrete variables were reported as percentages. Ordinary two-way ANOVA was used to compare the dimensions and percentages of patterns of the SN. Results The study identified six categories of exit patterns of the SN, type A (“Below and undivided”) occurred in a majority of cases (62.9%), a penta furcate branching pattern dominated the whole population, “Bifurcate” termination pattern was found in most SNs (90.3% and 87.1% for right and left limbs respectively) while the rest have the trifurcate termination pattern, with no side or sex-related variations. The average dimensions of SN were within normal ranges, and show no side-related differences but with a sex effect (are significantly higher in males than females), mean length of the SN in centimeters (length A: Males, right limbs = 30.58 ± 9.00; left limbs = 31.30 ± 6.20; Females, right = 26.07 ± 6.58; left = 26.30 ± 5.56), the mean level of termination of SN in centimeters (length B: Males, right = 8.5 ± 4; left = 8.2 ± 3.9; Females, right = 7.76 ± 3.8; left = 7.82 ± 3.5), mean SN diameters in millimeters: mean exit diameter (Males: right = 11.69 ± 1.92; left = 11.67 ± 2.16; Females, right = 8.41 ± 2.24; left = 9.28 ± 1.99), mean midthigh diameter (Males: right = 8.86 ± 1.56; left = 9.64 ± 1.88; Females, right = 7.12 ± 1.46; left = 8.28 ± 1.89), mean terminal end diameter (Males, right = 9.47 ± 2.07; left = 9.86 ± 2.32; Females, right = 7.5 ± 1.62; left = 8.4 ± 2.24). Conclusions Most SNs show normal anatomical characteristics with rare cases of sex-related dimorphism in the termination level and morphometry (length and diameter) of the nerve. The observed sexual dimorphisms in sciatic nerves are of great clinical and surgical interest and a warranty for more investigations in different populations, especially through the use of advanced techniques such as ultrasonographic anatomy techniques.

show abstract

Dual Kv7.2/3-TRPV1 modulators inhibit nociceptor hyperexcitability and alleviate pain without target-related side effects

Raveh,

Pen,

Silberman

et al. 2024

Pain

View full text Add to dashboard Cite

Persistent or chronic pain is the primary reason people seek medical care, yet current therapies are either limited in efficacy or cause intolerable side effects. Diverse mechanisms contribute to the basic phenomena of nociceptor hyperexcitability that initiates and maintains pain. Two prominent players in the modulation of nociceptor hyperexcitability are the transient receptor potential vanilloid type 1 (TRPV1) ligand-gated ion channel and the voltage-gated potassium channel, Kv7.2/3, that reciprocally regulate neuronal excitability. Across many drug development programs targeting either TRPV1 or Kv7.2/3, significant evidence has been accumulated to support these as highly relevant targets; however, side effects that are poorly separated from efficacy have limited the successful clinical translation of numerous Kv7.2/3 and TRPV1 drug development programs. We report here the pharmacological profile of 3 structurally related small molecule analogues that demonstrate a novel mechanism of action (MOA) of dual modulation of Kv7.2/3 and TRPV1. Specifically, these compounds simultaneously activate Kv7.2/3 and enable unexpected specific and potent inhibition of TRPV1. This in vitro potency translated to significant analgesia in vivo in several animal models of acute and chronic pain. Importantly, this specific MOA is not associated with any previously described Kv7.2/3 or TRPV1 class-specific side effects. We suggest that the therapeutic potential of this MOA is derived from the selective and specific targeting of a subpopulation of nociceptors found in rodents and humans. This efficacy and safety profile supports the advancement of dual TRPV1-Kv7.2/3 modulating compounds into preclinical and clinical development for the treatment of chronic pain.

show abstract

Sural hypersensitivity after nerve transection depends on anatomical differences in the distal tibial nerve of mice and rats

Cited by 4 publications

References 23 publications

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain

Morphologic and morphometric bilateral analysis and sexual dimorphism in sciatic nerves of adults: an anatomic investigation of cadaveric specimens in Uganda with implications on sciatic nerve neuropathologies

Dual Kv7.2/3-TRPV1 modulators inhibit nociceptor hyperexcitability and alleviate pain without target-related side effects

Contact Info

Product

Resources

About