Lenalidomide and thalidomide in the treatment of chronic pain

The immunomodulatory and anti-inflammatory drug thalidomide was first introduced in 1957 as a sleep aid and treatment for morning sickness. It was subsequently removed from the market due to severe teratogenic side effects and then returned to the market as a treatment for myelodysplastic syndrome and multiple myeloma. Lenalidomide is an analog of thalidomide with similar efficacy but improved side-effect profile. There are reports and studies of both agents for the treatment of chronic pain, especially complex regional pain syndrome (CRPS). Effective medical and interventional therapies for CRPS are limited. The use of novel immunomodulatory and anti-inflammatory drugs such as thalidomide and lenalidomide may offer a new approach to the treatment of CRPS.

The mechanism of action, adverse effect profile, and regulatory history of thalidomide and lenalidomide will be reviewed. The literature search for pain treatment includes case series and preliminary trials for CRPS, and case reports and case series for other chronic pain conditions.

Lenalidomide has a more favorable adverse effect profile compared to its parent compound thalidomide. Both agents, however, have significant potential adverse effects. Evidence of efficacy for chronic pain syndromes such as CRPS remains limited. Further studies are needed before these agents can be recommended for use in CRPS or other chronic pain syndromes.