The Role of Peptides in Pain Management

Peptide medications have emerged as therapeutic options for a myriad of medical conditions. Although peptide medications were first introduced more than a century ago with the development of insulin for diabetes mellitus (DM), their market has grown substantially over the past 2 decades.1 The highest rate of peptide medications approved by the Food and Drug Administration (FDA) were from 2020 to 2023, and recent reports expect the therapeutic peptide market to grow to $68.83 billion by 2028, increasing from $45.66 billion in 2024.1 Currently, the top-selling peptide medications are primarily glucagon-like peptide-1 receptor agonists utilized in the treatment of DM and obesity.1 However, in the pain management field, peptide therapeutics have had a more static evolution, with only 1 FDA-approved peptide medication available. Derived from the marine snail Conus magnus, ziconotide is a synthetic peptide that selectively binds to presynaptic N-type calcium channels on nociceptive afferent neurons in the dorsal horn of the spinal cord, inhibiting release of pain-related neurotransmitters to decrease nociception.2 This medication cannot penetrate the blood-brain barrier, requiring intrathecal pump drug delivery systems, and is most commonly indicated to treat severe chronic pain refractory to systemic analgesics. Although withdrawal is not present, neuropsychiatric side effects may limit its use. Ziconotide was the first peptide toxin approved by the FDA in 2004,2 and its discovery has stimulated a wave of research on peptide therapeutics in pain management. This article intends to highlight the discoveries, clinical applications, and limitations of peptides in pain management based on published research. As the popularity of peptide therapeutics continues to grow, it is paramount that physicians be aware of the literature surrounding peptides for pain management to perform patient-centered care.