ABSTRACT
Numerous studies have shown that pain sensation is affected by various immune molecules, such as cytokines, in tissues comprising the sensory pathway. Specifically, it has been shown that interleukin (IL)-17 promotes pain behaviour, but IL-10 suppresses it. IL-27 has been reported to have an anti-inflammatory effect through regulation of T cell differentiation, resulting in reduced IL-17 and induction of IL-10. Thus, we hypothesised that IL-27 would have some regulatory role in pain sensation. Here, we provide evidence that endogenous IL-27 constitutively controls thresholds for thermal and mechanical sensation in physiological and pathological conditions. Mice lacking IL-27 or its receptor WSX-1 spontaneously showed chronic pain-like hypersensitivity. Reconstitution of IL-27 in IL-27-deficient mice reversed thermal and mechanical hypersensitive behaviours. Thus, unlike many other cytokines induced by inflammatory events, IL-27 appears to be constitutively produced and to control pain sensation. Furthermore, mice lacking IL-27/WSX-1 signalling showed additional hypersensitivity when subjected to inflammatory or neuropathic pain models. Our results suggest that the mechanisms underlying hypersensitive behaviours caused by the ablation of IL-27/WSX-1 signalling are different from those underlying established chronic pain models. This novel pain control mechanism mediated by IL-27 might indicate a new mechanism for the chronic pain hypersensitivity.
Subject(s)
Interleukin-27/metabolism , Adolescent , Animals , Behavior, Animal , Capsaicin/toxicity , Child , Electrophysiology , Humans , Immunohistochemistry , Interleukin-27/genetics , Male , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/metabolism , Nociceptive Pain/chemically induced , Nociceptive Pain/metabolism , Nociceptors/drug effects , Nociceptors/metabolism , Pain Threshold/drug effects , Pain Threshold/physiology , Receptors, Cytokine/genetics , Receptors, Cytokine/metabolism , Receptors, InterleukinABSTRACT
BACKGROUND: The oral thrombopoietin (TPO) receptor agonist lusutrombopag (Mulpleta®) was developed to improve thrombocytopenia in patients with chronic liver disease prior to elective invasive medical procedures. Mulpleta® was first approved for use in Japan in 2015 and in the USA in 2018. In the present report, we discuss a case in which pain management was performed during left renal artery embolization via continuous epidural anesthesia following oral administration of lusutrombopag. To our knowledge, this is the first report to discuss the use of lusutrombopag prior to epidural anesthesia. CASE PRESENTATION: The patient was a 78-year-old woman scheduled to undergo renal artery embolization to address a 3-cm aneurysm of the left renal artery. Fourteen days prior to the scheduled embolization procedure, the urologist was asked to insert an epidural catheter for perioperative and postoperative analgesia. Type C chronic cirrhosis was observed, and platelet count was 5.6 × 104/µL. Eleven days prior to embolization, oral lusutrombopag was initiated at a dosage of 3 mg/day (day 1). Oral lusutrombopag therapy was continued for 5 days, and platelet count on day 11 (i.e., the day prior to surgery) was 12.6 × 104/µL. An epidural catheter was inserted on day 12, following which embolization was performed. Platelet count on day 13 was 11.0 × 104/µL, and the catheter was removed on day 14. No symptoms of epidural hematoma or thrombosis were observed during the patient's disease course. CONCLUSIONS: As lusutrombopag is a relatively safe platelet-increasing agent, we believe that this drug can serve as a potential treatment option when performing elective epidural anesthesia in patients with chronic liver disease complicated by thrombocytopenia.
