Thalidomide was introduced as a sedative and antiemetic agent to the European 
market in the late 1950s. However, it soon became clear that a hitherto 
unheard-of incidence of severe birth defects was due to the maternal use of 
thalidomide and the drug was withdrawn from the market. Despite its 
teratogenesis, thalidomide is currently being rediscovered because of its known 
spectrum of anticachectic, antiemetic, mildly hypnotic, anxiolytic, 
anti-inflammatory, antiangiogenic, and analgesic properties. The mechanism of 
action of thalidomide is probably based on its immunomodulatory effect, namely 
the suppression of production of tumor necrosis factor alpha and the modulation 
of interleukins. A striking but not well-known finding is the effectiveness of 
thalidomide as an analgesic or analgesic adjuvant. During the early era of 
thalidomide use, the drug was shown to enhance the analgesic efficacy of a 
combined treatment with acetylsalicylic acid, phenacetin, and caffeine (APC) by 
testing "normal volunteers, using electrical stimulation of teeth." The 
combination of thalidomide and APC was superior to other combinations (APC 
alone, APC and codeine) with respect to both the total analgesic effect and the 
duration of this analgesic effect. In 1965 thalidomide was found to be effective 
in treating the painful subcutaneous manifestations of the leprosy-associated 
erythema nodosum leprosum, a condition for which it eventually was approved by 
the United States Food and Drug Administration in 1998. In an animal model of 
neuropathic pain (chronic constriction injury), thalidomide was shown to reduce 
both mechanical allodynia and thermal hyperalgesia. Recent studies documented 
the analgesic efficacy of thalidomide in treating painful mucocutaneous aphthous 
ulcers associated with HIV syndrome and Behcet's disease.However, to date there 
are no recent clinical trials that are specifically designed to explore the 
analgesic potential of thalidomide. In view of the current basic research and 
clinical findings,we suggest to investigate the potential benefits of 
thalidomide in severe pain conditions that respond poorly to common pain 
management approaches such as neuropathic pain, postherpetic neuralgia, or 
central pain phenomena. Because its mechanism of action is distinct from that of 
other drugs such as steroids, thalidomide offers the possibility of a combined 
treatment with other agents with nonoverlapping toxicities. We conclude that 
thalidomide, when used properly,may enrich the therapeutic regimen in the 
management of some pain-related conditions.