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Several intracellular signals are involved in the sexual dimorphism of chronic pain. Our previous studies demonstrated that the fat-mass and obesity-associated protein (FTO), a demethylase of RNA N6-methyladenosine, in the injured dorsal root ganglion (DRG) contributed to the development and maintenance of nerve injury-induced nociceptive hypersensitivity in male rats and male mice. However, whether these effects of DRG FTO are in a sex-dependent manner is still unknown. The present study sought to investigate the effect of intrathecal administration of a specific FTO inhibitor, meclofenamic acid (MA), on chronic constriction injury (CCI)-induced nociceptive hypersensitivity in female rats. Intrathecal injection of MA attenuated the CCI-induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia in both the induction and maintenance periods, without changing acute/basal pain and locomotor function, in female rats. Intrathecal MA also blocked the CCI-induced hyperactivations of neurons and astrocytes in the ipsilateral L4 and L5 dorsal horns of female rats. Mechanistically, intrathecal MA prevented the CCI-induced increase in the histone methyltransferase G9a expression and reversed the G9a-controlled downregulation of mu-opioid receptor and Kv1.2 proteins in the ipsilateral L4 and L5 DRGs of female rats. These findings indicate that the effects of the FTO inhibitor on nerve injury-induced nociceptive hypersensitivity in female rats are similar to those in male rats reported previously. Our data also further confirm the role of DRG FTO in neuropathic pain and suggest potential clinical application of the FTO inhibitors for the prevention and treatment of this disorder in both men and women.

Sickle cell disease (SCD), a hemoglobinopathy, causes sickling of red blood cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme pain. A vast majority of SCD patients experience pain on a chronic basis, and many turn to opioids to provide limited relief. The side effects that come with chronic opioid use push for research into understanding the specific mechanisms of SCD-associated chronic pain. Current advances in SCD-associated pain have focused on alterations in the pain pathway including nociceptor sensitization and endogenous pain inducers. This article reviews the underlying pathophysiology of SCD, potential pain mechanisms, current treatments and their mechanism of action, and future directions of SCD-associated pain management. The information provided could help propel research in SCD-associated chronic pain and uncover novel treatment options for clinicians.

There is a petition for tight control of ketamine from the Chinese government to classify ketamine as a Schedule I drug, which is defined as a drug with no currently accepted medical use but a high potential for abuse. However, ketamine has unique properties that can benefit different patient populations. Scholars from the Translational Perioperative and Pain Medicine and the International Chinese Academy of Anesthesiology WeChat groups had an interactive discussion on ketamine, including its current medical applications, future research priorities, and benefits versus risks. The discussion is summarized in this manuscript with some minor edits.