Predictive value of a diagnostic block in focal nerve injury with neuropathic pain when surgery is considered.

OBJECT: In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief. We evaluated the predictive value of a block on the outcome of surgery. METHODS: In total, three blocks were performed at two week intervals. Patients were blinded to injections containing lidocaine 1% and a placebo was included. Surgery was offered regardless of the effect of the blocks. Twenty-four patients received 72 blocks. Sixteen patients opted for surgery, 5 patients refrained from surgery, and in 3 the blocks provided permanent pain relief. The predictive ability of the block on the outcome of surgery was assessed by calculating the area under a Receiver Operating Characteristic curve (AUC). RESULTS: The AUC of the first lidocaine block was 0.35 with a 95% confidence interval from 0.077 to 0.62. At 95% confidence (two-sided), the AUC is less than 0.62, and hence the predictive ability of the block was poor. The outcome of the second lidocaine block and saline block did not change the conclusion of the first block. CONCLUSIONS: We conclude that the use of blocks to select patients for surgery should be critically appraised. PERSPECTIVE: A pain relieving response to one open block is currently considered mandatory before patients with focal nerve injury and neuropathic pain are offered surgery. Blinded blocks including a placebo show that responses for selection should be carefully interpreted because they may not be as predictive as generally presumed.

A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF.

The clinical outcome of microsurgical repair of an injured peripheral nerve with an autograft is suboptimal. A key question addressed here is: can axon regeneration through an autograft be further improved? In this article the impact of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) on axon regeneration was compared after delivery to a 1cm long nerve autograft by gene therapy. To distinguish between early and late effects, regeneration was assessed at 2 and 20weeks post-surgery by histological, electrophysiological and functional analysis. BDNF, GDNF and NGF exhibited a spectrum of effects, including early stimulatory effects on axons entering the autograft and excessive axon growth and Schwann cell proliferation at 20weeks post-surgery. Persistent expression of these factors in autografts interfered with target cell reinnervation and functional recovery in a modality specific way. Autografts overexpressing VEGF displayed hypervascularization, while grafts transduced with CNTF and NT3 were indistinguishable from control grafts. These three factors did not have detectable pro-regenerative effects. In conclusion, autograft-based repair combined with gene therapy for three of the six growth factors investigated (BDNF, GDNF, NGF) showed considerable promise since these factors enhanced modality specific axon outgrowth in autografts. The remarkable and selective effects of BDNF, GDNF and NGF on motor or sensory regeneration will be exploited in future experiments that aim to carefully regulate their temporal and spatial expression since this has the potential to overcome the adverse effects on long-distance regeneration observed after uncontrolled delivery.