Upregulated TNF-α and lactate following ERK-SGK1 activation in the spinal dorsal horn underlies chronic postsurgical pain.

Skin/muscle incision and retraction (SMIR) during surgeries can lead to chronic postsurgical pain (CPSP). The underlying mechanisms are still unclear. In the present study, we showed that SMIR of the thigh induced phosphorylation of extracellular signal-regulated kinase (ERK), followed by serum- and glucocorticoid-inducible kinase-1 (SGK1) activation in the spinal dorsal horn. Intrathecal injection of PD98059, an ERK inhibitor, or GSK650394, a SGK1 inhibitor, significantly attenuated mechanical pain hypersensitivity in SMIR rats. The level of tumor necrosis factor α and lactate in spinal cord was significantly decreased by PD98059 or GSK650394 injection. Furthermore, PD98059 decreased the activation of SGK1 in the spinal dorsal horn. These results indicate that ERK-SGK1 activation followed by proinflammatory mediator release in the spinal dorsal horn underlies CPSP.

Botulinum toxin decreases hyperalgesia and inhibits P2X3 receptor over-expression in sensory neurons induced by ventral root transection in rats.

OBJECTIVES: We aim to determine the effects of Botulinum toxin type A (BTX-A) on neuropathic pain behavior and the expression of P2X(3) receptor in dorsal root ganglion (DRG) in rats with neuropathic pain induced by L5 ventral root transection (L5 VRT). METHODS: Neuropathic pain was induced by L5 VRT in male Sprague-Dawley rats. Either saline or BTX-A was administered to the plantar surface. Behavioral tests were conducted preoperatively and at predefined postoperative days. The expression of P2X(3) receptors in DRG neurons was detected by immunoreactivity at postoperative days 3, 7, 14, and 21. RESULTS: The number of positive P2X(3) neurons in the ipsilateral L5 DRG increased significantly after L5 VRT (P<0.001). This increase persisted for at least 3 weeks after the operation. No significant changes in P2X(3) expression were detected in the contralateral L5, or in the L4 DRGs bilaterally. Subcutaneous administration of BTX-A, performed on the left hindpaw at days 4, 8, or 16 post VRT surgery, significantly reduced mechanical allodynia bilaterally and inhibited P2X(3) over-expression induced by L5 VRT. CONCLUSIONS: L5 VRT led to over-expression of P2X(3) receptors in the L5 DRG and bilateral mechanical allodynia in rats. Subcutaneous injection of BTX-A significantly reversed the neuropathic pain behavior and the over-expression of P2X(3) receptor in nociceptive neurons. These data not only show over-expression of purinergic receptors in the VRT model of neuropathic pain but also reveal a novel mechanism of botulinum toxin action on nociceptive neurons.

Percutaneous posterior-lateral lumbar interbody fusion for degenerative disc disease using a B-Twin expandable spinal spacer.

Degenerative disc disease (DDD) causes gradual intervertebral space collapse, concurrent discogenic or facet-induced pain, and possible compression radiculopathy. A new minimal invasion procedure of percutaneous posterior-lateral lumbar interbody fusion (PPLIF) using a B-Twin stand-alone expandable spinal spacer (ESS) was designed to treat this disease and evaluated by follow-up more than 1 year. 12 cases with chronic low back pain and compressive radiculopathy due to DDD refractory were selected to conservative treatment. Under fluoroscopy in the posterior-lateral position, a K-wire was advanced into the intervertebral space and a dilator and working cannula were introduced into the disc space step by step. Discectomy and endplate scratching were performed through the cannula using pituitary forceps and endplate curettage. An ESS was inserted into the intervertebral space by a B-Twin expandable spinal delivery system after some bone graft chips implanted into the disc space. The ongoing study includes intraoperative difficulties, complications, radiologic evidence of fusion and clinical outcome as scored by pre- and postoperative questionnaires pertaining to pain intensity and degree of disability. The 12 procedures of lumbar interbody fusion using stand-alone expandable spinal system through percutaneous approach were successful. Radiologic study demonstrated fusion in a total of 11 cases and only 1 exception after more than 1 year visiting. The values of Visual Analog Scale (VAS) on movement and Oswestry Disability Index (ODI) dropped by more than 80 and 67.4%, respectively. Disk space heights averaging 9.0 mm before procedure were increased to 11.5 mm 1 month (a significant difference compared with preprocedure, P < 0.01) after surgery and stabilized at 10.8 mm upon final follow-up (a significant difference compared with preprocedure, P < 0.01). The results demonstrated that the percutaneous approach for posterior-lateral lumbar interbody fusion using expandable spinal system is a valuable micro-invasion method for the DDD patients and can achieve the same outcome as with other methods.