The main clinical manifestations of sickle cell disease (SCD) are the hemolytic anemia and acute vaso-occlusive crisis (VOCs), characterized by episodic, recurrent, and unpredictable acute pain. This pain complaint starts during infancy, and in addition to episodic acute pain, patients also report chronic pain throughout life. Management of pain is still a challenge for clinicians. Among patients, VOCs vary in frequency and severity.

Current treatment of pain is mostly reliant upon hydration, opioids and NSAIDs. Pain episodes are additionally managed with a multimodal approach (warmth, massage, distraction, acupuncture, biofeedback, self-hypnosis) and avoiding climate extremes.

Opioids are the major analgesic group that is commonly used for treating pain. However, opioid associated side effects, such as tolerance and opioid-induced hyperalgesia are significant problems associated with the long-term use.

VOCs might also require breakthrough pain management as vaso-occlusion and enhanced vasoconstriction exacerbate the continuous pain. as a general treatment strategy, hydroxyurea can decrease the frequency and severity of vasoocclusive processes. Also glutamine has received FDA approval for individuals over five years of age. Besides these, some alternative drug therapies such as ketorolac, tramadol fentanyl buccal tablet, NSAIDs, ketamine, gabapentine, Mg, rivapansel, sevuparine, crizanlizumab, prasugrel, apixaban, statins, cannabinoids and non pharmacological interventions such as TENS; cognitive behavioral therapy, biofeedback, hypnosis, massage etc. Are being used to prevent and/or treat pain conditions.

Conclusion Despite significant improvements in the understanding and management of SCD, still little progress has been made in the management of pain. Opioids and NSAIDs remain the mainstay of treatment of pain, but new classes of drugs are being tested to prevent and treat acute episodes.