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Skeletal muscle relaxants are frequently prescribed for low back pain and other musculoskeletal pain with or after failure of first-line treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs). While there can be benefits of using skeletal muscle relaxants in the short term, the long-term effects are unclear. These medications are heterogeneous and not chemically related and have several important adverse effects that should be considered given their widespread utilization. In the United States, carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine are FDA approved for acute musculoskeletal conditions. Baclofen, tizanidine, and dantrolene are approved for spasticity. There is no clear evidence to show superiority of one muscle relaxant over another in managing acute low back pain, and most studies only evaluate results at 12 weeks or less. Most guidelines and current evidence support short-term use for all medications discussed in this chapter.

Voltage-gated sodium channels (Nav) that initiate electrical signals in excitable nerve and muscle cells are molecular targets for drugs and acquire disease mutations. These ion channels were first discovered in 1952 by researchers Hodgkin and Huxley who published landmark papers in The Journal of Physiology. The three key features of sodium channels discovered were voltage-dependent activation, rapid inactivation, and selective ion conductance. Since that time, a total of nine sodium channels have been discovered. The Nav isoforms of most interest as analgesic targets are Nav 1.3, Nav 1.7, Nav 1.8, and Nav 1.9 as they play specific roles in the neurobiology of pain and serve as potential analgesic targets. Knowledge of these channels’ structure and function, as well as their alterations in chronic pain, are vital to understanding how current sodium channel antagonists work but also for future drug developments. Currently, sodium channel antagonists fall into four pharmacological classes including anti-arrhythmics, anticonvulsants, local anesthetics, and antidepressants (discussed in another chapter). The sodium channel antagonists discussed in this chapter are considered nonselective.