Treatment and management of pain in patients with sickle cell disease (SCD) should be individualized and not rely only on opioids, according to a new study published in the Journal of Pain Research.

However, research data on adjunct analgesics, such as lidocaine, ketamine, pregabalin, and gabapentin, as well as on nonpharmacological management of pain and vaso-occlusive crises in SCD are lacking.

“An adaptation of Richard Melzack’s multidimensional pain model –the neuromatrix theory– as a framework for conceptualizing sickle cell pain indicates that management of acute sickle cell pain should be multimodal and individualized,” the researchers wrote.

“Focusing solely on pain perception as an outcome may lead to the exclusion of an effective adjunct, which may not change pain scores, but it may improve physical function, and decrease markers of stress – and, thus, improve patient-reported quality of life.”

Read more about SCD treatment

The research team adapted an explanatory model for pain called “the neuromatrix theory of pain,” which was initially proposed in 1989 by Richard Melzack, a pain psychologist. The model suggests that the central nervous system (CNS) is not just a passive player in receiving pain signals, but instead, that pain is comprised of 3 output domains: cognitive, sensory, and affective.

This means that pain medications other than opioids, which focus exclusively on CNS pain signal reception and have significant adverse effects, could play an important role in pain management for patients with SCD while avoiding or reducing the adverse effects of opioids. In addition to lidocaine, ketamine, pregabalin, and gabapentin, the authors propose investigating the potential of antidepressants and nonpharmacological interventions for these patients.

The proposed approach would incorporate the multidimensional nature of pain as experienced by patients with SCD and might suggest new pain targets and measures of efficacy of clinical interventions. The authors recommend well-designed, multicenter randomized controlled trials to assess the potential of a multimodal pain management plan with adjunct medications and nonpharmacological interventions to reduce pain and improve the overall quality of life in SCD.


Kenney MO, Smith WR. Moving toward a multimodal analgesic regimen for acute sickle cell pain with non-opioid analgesic adjuncts: a narrative review. J Pain Res. 2022;15:879-894. doi:10.2147/JPR.S343069