Laser energy can be greatly absorbed by water in human tissues, which makes the water molecules boil and the intracellular and extracellular fluid evaporate rapidly, resulting in vaporization, ablation, and hemostasis. Due to advantages such as high energy and low penetration, lasers have been applied widely in for surgery in dermatology, urology, and other medical subspecialties. Netsch et al used a holmium laser to remove benign prostatic hyperplasia and found that the holmium laser safely and effectively ablated hyperplastic prostate tissue peri-operatively and obtained good clinical results . Zhu et al compared the efficacy and safety of the holmium laser and trans-urethral resection in primary non-muscular invasive bladder tumors and concluded that holmium laser treatment could markedly improve surgical efficiency, reduce peri-operative complications and improve safety in bladder tumor surgeries .
The application of lasers in spinal surgery is still in its early phase. In 1987, Choy et al used Nd:YAG laser ablation of herniated nucleus pulposus tissue to complete lumbar intervertebral disc decompression. However, the decompression was not carried out under direct vision, so there was a great risk of nerve root injury . With the development of percutaneous endoscopic technology, the percutaneous laser transmission system is combined with spinal endoscopy, the intervertebral disc tissue and nerve structure can be directly observed by the intervertebral foramen or interlaminar approach, and laser vaporization and ablation can be used to remove the nucleus pulposus tissue and decompress nerve roots more accurately, safely, and thoroughly. So far, multiple types of lasers have been used clinically, including the neodymium laser (Nd:YAG), holmium laser (Ho:YAG) and semiconductor laser [12, 13]. Among them, the wavelength of the holmium laser is 2.1 µm, the depth of tissue penetration is only ≤0.5 µm, and the beam is easily absorbed by water. Compared with other types of laser, the holmium laser creates less thermal damage to surrounding tissues such as the dural sac and nerve roots so it is more widely adopted in clinically. In the study of Ruetten et al , the holmium laser was combined with spinal epidural endoscopic surgery. When the holmium laser energy was controlled at 0.8 J (frequency 8 Hz), epidural scar tissues could be cut effectively and safely, improving the symptoms of chronic low back pain. Daehyun et al studied the risk of dural damage caused by the holmium laser in epidural endoscopy and found in cadaver experiments that when the holmium laser energy was set at 5 J, the holmium laser irradiation perpendicular to the dura induced more obvious dural damage compared with irradiation parallel to the dura. In addition, the degree of dural injury was more severe with more prolonged irradiation time. Therefore, they suggested that attention should be paid to the risk of dural injury when using the holmium laser in spinal epidural endoscopy .
Holmium laser technology has been widely applied in epidural endoscopy, but the application of the holmium laser in full-endoscopic spine surgery is still in its infancy. Holmium laser surgery and full-endoscopic spine surgery need "water" as the working medium, so the efficient combination of holmium laser technology and full-endoscopic spine surgery can provide advantages of both techniques, improving surgical efficiency and safety. Yeung et al  reported that endoscopic resection of the nucleus pulposus and decompression with the holmium laser was performed through the postero-lateral "Kambin triangle" approach to the intervertebral disc. The results of at least one-year follow-up after surgery showed that the rate of excellent and good clinical results was 83.6%. As a reliable tool for endoscopic minimally invasive surgery, the holmium laser can effectively complete rapid vaporization, ablation, and hemostasis of different structures such as the ligamentum flavum, nucleus pulposus, annulus fibrosus and bone wounds, and shorten the operation time for exposing the surgical target area and removing the intervertebral disc tissues. Meanwhile, during precise ablation, it can reduce the risk of nerve injury because it avoids most tissue injuries. Moreover, the holmium laser lateral opening is beneficial for dealing with the "blind area" in the long and narrow endoscopic channel that includes the horizontal dorsal ligamentum flavum of the intervertebral disc. Knight et al  reported that 48 patients with lumbar lateral recess stenosis underwent enlarged intervertebral foramenoplasty with the holmium laser endoscopically. This quickly removes hyperplastic osteophytes, protruding nucleus pulposus and epidural scar tissue, thus improving surgical efficiency.
One of the major technical difficulties in full-endoscopic spine surgery is intraoperative hemostasis. Hemostasis of the bone surface after arthroplasty is particularly difficult, and the visual field disturbance caused by surgical bleeding increases the operation time and risk. In traditional Elliquence radiofrequency surgery, it is necessary to place the radiofrequency tip on the tissue and convert its electrical energy into thermal energy so that the local tissue temperature rises to 60°C, causing protein denaturation and achieving hemostasis. As the conversion speed of electric energy to heat energy is slow, and the local tissue temperature rises slowly, the hemostatic efficiency of traditional Elliquence radiofrequency is low. In contrast, the holmium laser has high energy, the conversion of light energy to thermal energy is faster, and the energy can be quickly absorbed by the tissue to reach the hemostatic temperature, which makes the local tissue coagulate. In this study, it was found that the holmium laser effectively stopped bleeding not only of the soft tissue, but also of the bone surface after articular process resection. Effective intraoperative hemostasis can further improve safety and shorten surgical time. In this study, the operation time in group A (receiving the holmium laser treatment) was significantly shorter than that in group B (receiving traditional Elliquence radiofrequency treatment).
Clinically, lumbar disc herniation often is accompanied by discogenic low back pain caused by disc degeneration in addition to radiating pain to the lower limbs. However, 15-25% of patients still have discogenic lower back pain after nucleus pulposus removal . Full-endoscopic spine surgery can remove the herniated nucleus pulposus tissue, relieve nerve root compression, and effectively improve the symptoms of pain radiating to the lower limbs. However, whether full-endoscopic spine surgery can effectively relieve discogenic lower back pain is still controversial. In the study of Gibson et al , 70 patients with lumbar disc herniation underwent trans-foraminal percutaneous endoscopic lumbar discectomy (PELD), and their VAS scores for lower back pain and leg pain decreased from 5.7±2.7 points and 6.2±2.8 points before surgery to 2.5±2.5 points and 1.9±2.6 points two years after surgery, respectively. Ruetten et al  reported that among the 232 patients with lumbar disc herniation after PELD, the improvement rate of radiating pain in the lower limbs was 96%, but lower back pain was not improved significantly compared with pre-operative pain. Ten patients needed open surgery due to persistent low back pain after the initial surgery.
To further clarify the improvement of lower back pain and lower limb radiating pain after full-spinal endoscopy combined with holmium laser surgery, the VAS scores for lower back pain and lower limb radiating pain were recorded, respectively. The preoperative pain symptoms were similar in the two groups. Postoperative lower back pain was relieved by full-spinal endoscopy in both groups, indicating that "flowing water" as a surgical medium in full-endoscopic spine surgery can remove chronic pain-causing substances accumulated in the "herniated intervertebral disc" effectively . In addition, whether the holmium laser or Elliquence radiofrequency was used in the intervertebral disc, thermal effects are produced, inhibiting inflammatory factors that cause pain and achieving local physiotherapy to relieve the symptoms of low back pain in both groups . However, in this study, the VAS scores for lower back pain in the holmium laser treatment group were significantly lower than those in the Elliquence radiofrequency treatment group at all time points after surgery. We hypothesized that the tissue damage in the intervertebral disc nucleus pulposus and annulus fibrosus caused by the holmium laser was significantly smaller than that using Elliquence radiofrequency, thus reducing the secretion of inflammatory factors such as prostaglandins and interleukins that stimulate pain nerve fibers . In addition, the concentration of holmium laser energy can accurately inactivate granulation tissue and nociceptive nerve fibers in the annulus fibrosus, and further reduce pain in the intervertebral disc. Last but not least, lumbar nucleus pulposus (NP) resides in a hypoxic microenvironment, which is essential for maintaining normal cellular metabolism and protein synthesis. Once the blood vessel grows into the NP and disrupts the hypoxic microenvironment, the subsequent oxidative stress induces NP degeneration to cause lower back pain. The expression of oxidative stress markers, including pentosidine and advanced glycation end products (AGEs), is increased in the degenerative human NP . Excessive reactive oxygen species (ROS) was concluded to be a critical mediator in the pathogenesis of degenerative disc conditions and potential therapeutic target. Antioxidant NAC significantly abrogated the catabolic effect of excessive ROS in vitro and in vivo. Therefore, oxidative stress occurred in lumbar NP played a critical role in accelerating degeneration to cause discogenic lower back pain. Inhibition of the excessive oxidative stress has become a therapeutic target for controlling discogenic lower back pain. Recently, more studies showed laser was widely for the cosmetic surgery due to its effective inhibition on oxidative stress. Weng et al. indicated laser treatment increased the level of enzymatic antioxidant including uperoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to elucidate the mechanism of laser nonablative rejuvenation in the established primary skin fibroblasts model . Additionally, low-level laser therapy demonstrated favorable effects in modulating the oxidative stress by decreased ROS and increased activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) to improve regenerative capacity of dystrophic muscle cells in the experimental model of Duchenne muscular dystrophy (DMD) . Therefore, holmium laser improves the symptoms of discogenic lower back pain by potential reducing oxidative stress in the NP. There was no significant difference in the VAS score for postoperative lower limb radiating pain or the ODI score between the two groups, indicating that either the holmium laser or Elliquence radiofrequency can achieve effective nerve decompression in a full-endoscopic spine surgery and relieve the symptoms of lower limb radiating pain and improve the quality of life of the patients.
Although the holmium laser was applied initially in full-endoscopic spine surgery and achieved good clinical results, there are still some shortcomings in the application of the holmium laser in full-endoscopic spine surgery. Firstly, the current holmium laser generator has the disadvantages of large volume, noise, difficulty of fixing the laser sheath during surgery, and it causes pollution easily. Secondly, the lack of minimally invasive instruments matched with laser surgery causes difficulties during surgery and prolongs the operative time. Thirdly, holmium laser parameters need to be further studied to ensure the optimal effect of tissue ablation and hemostasis. Lastly, the mechanism of improved postoperative lower back pain and inhibition effects of oxidative stress of the holmium laser needs to be further investigated. At present, there is an urgent need to develop a new laser generator and related minimally invasive instruments to further improve operation efficiency and safety, facilitate the population for which full-spinal endoscopy combined with holmium laser surgery, and improve the therapeutic effect in patients with lumbar disc herniation, thus relieving the burden of patients and society.