Cervical myelopathy responses to extracts derived from combustible cigarettes and heated tobacco products: in vivo and in vitro evidence.

Abstract

Degenerative cervical myelopathy (DCM) is a progressive spinal cord disorder, yet modifiable risk factors that accelerate its progression remain poorly understood. While cigarette smoking worsens surgical outcomes, its influence on disease progression under conservative management is unclear. Heated tobacco products (HTPs) are increasingly used worldwide, but their neurological effects remain unexamined. Authors of this study analyzed the effects of extracts derived from combustible cigarettes and HTPs on the progression of cervical myelopathy and determined whether combustible cigarettes and HTPs exert similar effects. Male Sprague Dawley rats (8 weeks old) underwent laminectomy only (sham group) or cervical spinal cord compression surgery and received intraperitoneal injections of saline (compression model [CM] group), cigarette smoke extract (CSE; compression model based on combustible cigarettes [cCM group]) or HTP extract (compression model based on heated tobacco products [hCM group]) every 5 days for 10 weeks. Motor and sensory function were assessed using the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale and the von Frey test, respectively. Histological evaluation was performed postmortem. In vitro, differentiated rat pheochromocytoma (PC12) cells were exposed to CSEs prepared from combustible cigarettes (cCSE) or HTPs (hCSE), and neurite length, cell viability, and apoptosis rates were assessed after 24 hours. The median BBB scale scores at 10 weeks postoperatively were significantly lower in the cCM (median 11 [IQR 11-11], p < 0.01) and hCM (11 [10-11], p < 0.01) groups than in the CM group (13 [13-15]). Hind paw withdrawal thresholds were higher in the cCM (median 26.0 g [IQR 26.0-60.0 g], p < 0.001) and hCM (26.0 g [26.0-60.0 g], p < 0.001) groups than in the CM group (15.0 g [10.0-15.0 g]). Histological analysis revealed increased neuronal loss, gray matter cavitation, and white matter demyelination. In PC12 cells, both extracts reduced neurite length (cCSE 13.4 ± 1.1 μm or hCSE 23.7 ± 11.4 μm vs untreated control 38.2 ± 15.4 μm, p < 0.001 for both), decreased viability (cCSE 0.041 ± 0.007 or hCSE 0.047 ± 0.007 vs untreated control 0.070 ± 0.015, p < 0.01 for both), and increased apoptosis (cCSE 53.6% ± 0.8% or hCSE 52.5% ± 1.2% vs untreated control 6.1% ± 1.0%, p < 0.01 for both). Both combustible cigarette and HTP extracts exacerbated neurological deterioration in a cervical myelopathy model. HTPs, despite their perceived safety, exhibited detrimental effects comparable to those from combustible cigarettes. These findings highlight the need to address all forms of tobacco use in patients with DCM treated conservatively.