Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

Abstract

Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

Molecular Transport through a Biomimetic DNA Channel on Live Cell Membranes

“…Therefore, we first studied if the DNA nanopores could successfully penetrate live cell plasma membranes and transport ions into the cells. Herein, we chose a primary culture of dissociated dorsal root ganglia (DRG) neurons as a cell model. , DRG neurons are the key to controlling sensory responses that involve a high volume of ion transport through the membrane in the peripheral nervous system . We first incubated the DRG neurons with fluorescently labeled DNA nanopores and used confocal microscopy to study the insertion of DNA nanopores on the plasma membrane of DRG neurons.…”

“…35,36 DRG neurons are the key to controlling sensory responses that involve a high volume of ion transport through the membrane in the peripheral nervous system. 37 We first incubated the DRG neurons with fluorescently labeled DNA nanopores and used confocal microscopy to study the insertion of DNA nanopores on the plasma membrane of DRG neurons. As shown in Figure 4A, the fluorescence signals could be observed on the cell membranes with incubation of 50 nM DNA nanopores at 4 °C for 40 min.…”

Perioperative Sleep Disorder: A Review

“…Current literature is largely supportive of perioperative sleep disturbance as a risk factor for post-operative pain, but the specific mechanisms are not fully elucidated. A conjecture is that perioperative short-term sleep deprivation may increase the expression and activity of L-type calcium channels in the lumbar dorsal root ganglion, delaying recovery from post-operative pain, and blocking these channels decreases the effects of sleep deprivation ( 58 ).…”

A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery

“…Endoscopic nasal sinus surgery is a nasal and sinus surgery carried out by endoscopy, especially it can directly insight into the deep nasal cavity and sinus, and is suitable for cleaning the lesions in deep depressions and fissures, to help restore the ventilation and drainage function of the nasal and sinus [ 11 ]. However, endoscopic nasal sinus surgery is often associated with postoperative pain and postoperative sleep disorder [ 12 ], then aggravate the severity of postoperative pain and slow the recovery of patients [ 13 , 14 ].…”