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drug was withdrawn from the market.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.