<p>Activity-dependent paresthesias associated with Gabapentin therapy: a case report Maxime Debrosse, MD, Larry Driver, MD Department of Pain Medicine, University of Texas - MD Anderson Cancer Center, Houston, Texas</p><p>Gabapentin is one of the most commonly prescribed drugs for paresthesias. However those symptoms are not known to be a side effect of Gabapentin. We present the case of a 38-year-old man with a history of sacral chordoma, status post partial sacrectomy and who developed burning buttock pain in the aftermath of the surgery. He was started on Gabapentin 900mg daily and the pain improved. However, two years later, he developed numbness in his arms during low-intensity physical activities, such as holding a phone to his ears for long periods of time. The numbness improved with the arms at rest. Dose reduction of the Gabapentin to 300mg daily resolved the numbness. Several research articles have suggested the concept of muscle compensatory vasodilation. In that model, agonism of beta-2 adrenergic receptors on the endothelial cell surface by epinephrine causes release of nitric oxide, which leads to vasodilation (1). That blunted vasodilatory response may cause paresthesia due to inward axonal potassium currents that occur during transient ischemia (2). Concurrently, an increasing number of studies demonstrate that Gabapentin acts as an alpha-2 adrenergic agonist, which reduces catecholamine release (3, 4). We propose that activity-dependent paresthesias may be a dose-dependent result of gabapentin-mediated inhibition of nitric oxide through reduced beta-2 adrenergic agonism.</p><p>References 1) Joyner MJ, Casey DP. Muscle blood flow, hypoxia, and hypoperfusion. J Appl Physiol (1985). 2014 Apr 1;116(7):852-7. 2) Mogyoros I, Bostock H, Burke D. Mechanisms of paresthesias arising from healthy axons. Muscle Nerve. 2000 Mar;23(3):310-20. 3) Tanabe M, Takasu K, Kasuya N, Shimizu S, Honda M, Ono H. Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. Br J Pharmacol. 2005 Mar;144(5):703-14. 4) Hayashida K, DeGoes S, Curry R, Eisenach JC. Gabapentin activates spinal noradrenergic activity in rats and humans and reduces hypersensitivity after surgery. Anesthesiology. 2007 Mar;106(3):557-62.</p>