We as regional anesthesiologists often use peripheral nerve blocks as a modality for intraoperative analgesia, but it is not well understood whether regional anesthesia can play a role beyond simple interruption of peripheral nerve conduction. Several published manuscripts in recent years on the potential non-analgesic applications of regional anesthesia encourage us to expand its role from intraoperative to the perioperative period. However, its clinical advantages are not fully disclosed and even its overall beneficial effect on patient outcome is still controversial (1).
The role of inflammation in the development of neuropathic pain has been explained earlier (2), which implies the therapeutic effects of sympathetic block in the treatment of chronic neuropathic pain disorders such as complex regional pain syndrome. The novel finding is the correlation between inflammation and the development of acute pain which has been proposed in a recent animal study (3). Regional anesthesia can play its anti-inflammatory role by anti-sympathetic effects (4) as well as anti-inflammatory properties of administered local anesthetics (5). However, the contribution of anti-inflammatory effects to overall clinical effects of peripheral nerve block is not well understood. This needs to be clarified in more meticulous trials addressing drugs and possibly techniques with more differentiated mechanisms of action. If elucidated, it may turn our views from simple interruption of impulse conduction in peripheral nerves to the possible anti-inflammatory mechanisms.
When reviewing the contribution of regional anesthesia to the postoperative pain and inflammation control, we should notice that ‘nerve block’ is just one side of the coin, while the other side, ‘nerve stimulation’ is even more interesting. Studies in recent years explain the role of vagus nerve stimulation (VNS) in the suppression of systemic inflammatory response known as ‘cholinergic anti-inflammatory pathway’ (6). It has been shown in animal studies that VNS reduces systemic levels of pro-inflammatory cytokines and Tumor Necrosis Factor (TNF) (7–9). This novel finding may have implications for postoperative period regarding the fact that uncontrolled inflammation plays an important role in the hyperglycemia, sepsis, shock and their consequent morbidity and mortality of critically ill patients.
VNS is currently used for its therapeutic effects in refractory epilepsy (10) and depression (11), and may be used for the treatment of chronic heart failure (12), portal hypertension (13) and eating disorders (14) in the future. Today application of VNS requires implantation of a stimulating electrode surgically (15). This procedure is invasive and has its specific complications (16, 17), which reduces its overall clinical benefit in the perioperative setting. However, favorable anti-inflammatory effects of VNS as well as its new potential perioperative applications such as therapeutic profile in the traumatic brain injury (18, 19) necessitates the development of a more feasible and less invasive approach to the nerve. Regarding the evolution in ultrasound imaging technology, it is expectable to better visualize the branches of vagus nerve and make them available for regional anesthesiologist with minimally invasive approaches. If so, this will expand the field of regional anesthesia from operating room to intensive care units in the near future.
Dabu-Bondoc SM. Regional anesthesia and perioperative outcome: what is new? Curr Opin Anaesthesiol 2004; 17 (5) : 435 -9
Kieseier BC, Hartung HP, Wiendl H. Immune circuitry in the peripheral nervous system Curr Opin Neurol 2006; 19 (5) : 437 -45
Rokyta R, Stopka P, Holecek V, Krikava K, Pekarkova I. Direct measurement of free radicals in the brain cortex and the blood serum after nociceptive stimulation in rats Neuro Endocrinol Lett 2004; 25 (4) : 252 -6
Czura CJ, Tracey KJ. Autonomic neural regulation of immunity J Intern Med 2005; 257 (2) : 156 -66
Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication? Anesthesiology 2000; 93 (3) : 858 -75
Pavlov VA, Tracey KJ. The cholinergic anti-inflammatory pathway Brain Behav Immun 2005; 19 (6) : 493 -9
Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin Nature 2000; 405 (6785) : 458 -62
Pavlov VA, Tracey KJ. Controlling inflammation: the cholinergic anti-inflammatory pathway Biochem Soc Trans 2006; 34 (Pt 6) : 1037 -40
Borovikova LV, Ivanova S, Nardi D, Zhang M, Yang H, Ombrellino M, et al. Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation Auton Neurosci 2000; 85 (1–3) : 141 -7
Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response J Neurosurg 2011; 115 (6) : 1248 -55
Martin JL, Martin-Sanchez E. Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: Variable results based on study designs Eur Psychiatry 2012; 27 (3) : 147 -55
Sabbah HN. Electrical vagus nerve stimulation for the treatment of chronic heart failure Cleve Clin J Med 2011; 78 (Suppl 1) : S24 -9
Bockx I, Verdrengh K, Vander Elst I, van Pelt J, Nevens F, Laleman W, et al. High-frequency vagus nerve stimulation improves portal hypertension in cirrhotic rats Gut 2012; 61 (4) : 604 -12
Pardo JV, Sheikh SA, Kuskowski MA, Surerus-Johnson C, Hagen MC, Lee JT, et al. Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity: an observation Int J Obes (Lond) 2007; 31 (11) : 1756 -9
Kawai K. [Vagus nerve stimulation for intractable epilepsy: implantation of vagus nerve stimulator] No Shinkei Geka 2008; 36 (11) : 979 -89
Spuck S, Tronnier V, Orosz I, Schonweiler R, Sepehrnia A, Nowak G, et al. Operative and technical complications of vagus nerve stimulator implantation Neurosurgery 2010; 67 (2 Suppl Operative) : 489 -94
Murr NI, Azar NJ. Severe new seizures after initiation of vagus nerve stimulation therapy Epilepsy Behav 2011; 22 (2) : 398 -400
Kumaria A, Tolias CM. Is there a role for vagus nerve stimulation therapy as a treatment of traumatic brain injury? Br J Neurosurg 2012;
Smith DC, Modglin AA, Roosevelt RW, Neese SL, Jensen RA, Browning RA, et al. Electrical stimulation of the vagus nerve enhances cognitive and motor recovery following moderate fluid percussion injury in the rat J Neurotrauma 2005; 22 (12) : 1485 -502