Your browser doesn't support javascript.
loading
Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats.
Bakare, Ahmed Olalekan; Stephens, Kimberly; Sanchez, Karla R; Liu, Vivian; Zheng, Lei; Goel, Vasudha; Guan, Yun; Sivanesan, Eellan.
Afiliación
  • Bakare AO; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Stephens K; Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
  • Sanchez KR; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
  • Liu V; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zheng L; Department of Computer Science, Johns Hopkins Whiting School of Engineering, Baltimore, Maryland, USA.
  • Goel V; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Guan Y; Department of Anesthesiology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Sivanesan E; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Reg Anesth Pain Med ; 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38844412
ABSTRACT

BACKGROUND:

Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity.

METHODS:

Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques.

RESULTS:

SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated.

CONCLUSION:

SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Reg Anesth Pain Med Asunto de la revista: ANESTESIOLOGIA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Reg Anesth Pain Med Asunto de la revista: ANESTESIOLOGIA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido