Covering the proximal nerve stump with chondroitin sulfate proteoglycans prevents traumatic painful neuroma formation by blocking axon regeneration after neurotomy in Sprague Dawley rats

Autor: Xiaolin Liu, Li-Hua Zhou, Zhe-Hui Tu, Qingtang Zhu, Yao Zhi, Yuan-Yuan Wang, Fan-Bin Gu, Fu-Lin He, Shuai Qiu, Jian-Long Zou
Rok vydání: 2021
Předmět:
rho GTP-Binding Proteins
Pathology
medicine.medical_specialty
animal structures
Administration
Topical
medicine.medical_treatment
Growth Cones
Interleukin-1beta
Substance P
Rats
Sprague-Dawley
Cicatrix
Neuroma
Random Allocation
Sciatica
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Peripheral Nervous System Neoplasms
Ganglia
Spinal
medicine
Animals
Iridoids
Single-Blind Method
Axon
Traumatic neuroma
Behavior
Animal
business.industry
Interleukin-17
Neurectomy
General Medicine
Neurotomy
medicine.disease
Axons
Nerve Regeneration
Rats
medicine.anatomical_structure
Chondroitin Sulfate Proteoglycans
chemistry
030220 oncology & carcinogenesis
Peripheral nerve injury
Gelatin
Neuralgia
Female
Sciatic nerve
Sciatic Neuropathy
business
030217 neurology & neurosurgery
Zdroj: Journal of Neurosurgery. 134:1599-1609
ISSN: 1933-0693
0022-3085
Popis: OBJECTIVE Neuropathic pain caused by traumatic neuromas is an extremely intractable clinical problem. Disorderly scar tissue accumulation and irregular and immature axon regeneration around the injury site mainly contribute to traumatic painful neuroma formation. Therefore, successfully preventing traumatic painful neuroma formation requires the effective inhibition of irregular axon regeneration and disorderly accumulation of scar tissue. Considering that chondroitin sulfate proteoglycans (CSPGs) can act on the growth cone and effectively inhibit axon regeneration, the authors designed and manufactured a CSPG-gelatin blocker to regulate the CSPGs’ spatial distribution artificially and applied it in a rat model after sciatic nerve neurectomy to evaluate its effects in preventing traumatic painful neuroma formation. METHODS Sixty female Sprague Dawley rats were randomly divided into three groups (positive group: no covering; blank group: covering with gelatin blocker; and CSPG group: covering with the CSPG-gelatin blocker). Pain-related factors were evaluated 2 and 8 weeks postoperatively (n = 30). Neuroma growth, autotomy behavior, and histological features of the neuromas were assessed 8 weeks postoperatively (n = 30). RESULTS Eight weeks postoperatively, typical bulb-shaped neuromas did not form in the CSPG group, and autotomy behavior was obviously better in the CSPG group (p < 0.01) than in the other two groups. Also, in the CSPG group the regenerated axons showed a lower density and more regular and improved myelination (p < 0.01). Additionally, the distribution and density of collagenous fibers and the expression of α–smooth muscle actin were significantly lower in the CSPG group than in the positive group (p < 0.01). Regarding pain-related factors, c-fos, substance P, interleukin (IL)–17, and IL-1β levels were significantly lower in the CSPG group than those in the positive and blank groups 2 weeks postoperatively (p < 0.05), while substance P and IL-17 remained lower in the CSPG group 8 weeks postoperatively (p < 0.05). CONCLUSIONS The authors found that CSPGs loaded in a gelatin blocker can prevent traumatic neuroma formation and effectively relieve pain symptoms after sciatic nerve neurotomy by blocking irregular axon regeneration and disorderly collagenous fiber accumulation in the proximal nerve stump. These results indicate that covering the proximal nerve stump with CSPGs may be a new and promising strategy to prevent traumatic painful neuroma formation in the clinical setting.
Databáze: OpenAIRE
Externí odkaz: