Tramadol Induced Paradoxical Hyperalgesia

Opioids have been the mainstay analgesics for postoperative, cancerous, andchronic noncancerous pain. Common concerns regarding the use of opioidsinclude the development of physical dependence and addiction. However, as apotential complication of opioid therapy, opioid-induced hyperalgesia (OIH) is oftenoverlooked. That is, patients receiving opioids to control their pain may paradoxicallybecome more sensitive to pain as a consequence of opioid therapy. OIH is a veryimportant issue because it may complicate the clinical course of pain treatment andeven worsen the suffering of patients receiving opioids because of the developmentof excruciating pain.Three OIH types were defined: 1) in the context of maintenance dosing andwithdrawal, 2) at very high or escalating doses, and 3) at ultra-low doses. In theliterature, most attention has been paid to the first 2 forms, and almost all cases ofreported OIH have been ascribed to morphine administration. The third form of OIHhas not been documented in humans, although it has been observed in animals.We present 2 cases of OIH resulting from administration of tramadol, which is asynthetic analogue of codeine and exhibits 10-fold less affinity for mu-opioidreceptors, in patients suffering from chronic pain. The 2 cases presented herein implythe importance of recognizing OIH in patients medicated with tramadol if analgesiceffects are lost in the context of dose titration, when generalized pain is reportedwithout any evidence of disease exacerbation.While OIH associated with ultra-low dose opiates seems to be quite rare, if it issuspected, switching to other drugs and an appropriate treatment should beconsidered.Key words: Opioid-induced hyperalgesia, opioids, chronic pain, serotoninsyndrome, tramadol, ketamine