GABA_A receptors as targets for the management of pain-related disorders: Historical perspective and update

Background: Chronic pain is treated most commonly with opioid analgesics, anti-inflammatory steroids and nonsteroidal anti-inflammatory drugs. Method: However, these compounds are not uniformly effective and their clinical use is constrained by unwanted side effects. GABAergic neurons are located in spinal nociceptive circuits suggesting that drugs with affinity at these receptors, including benzodiazepine-like drugs, may provide an alternative to opioids for the treatment of pain. However, systemically administered conventional benzodiazepines fail to produce antihyperalgesic effects, likely due to their concurrent sedative properties. Results: Recent evidence suggests that by targeting specific benzodiazepine-sensitive GABA_A receptor subtypes, the sedative properties of benzodiazepines can be circumvented and these compounds may be useful alternatives to opioids for the treatment of chronic pain. Conclusion: The present review provides an overview of the GABA_A receptor subtypes involved in pain transmission as well as implications for the development of analgesic medications.