There is emerging evidence that disorders of the endogenous opioid system may play a role in the pathobiology of CKD-aP. An important longstanding observation has been the very clear recognition that use of opiates that bind to mu-opioid receptors predictably cause itching. There are three primary types of opioid receptors, mu, kappa, and delta. All three are found in sensory nerve endings in the skin. Recent knowledge has pointed to mu receptors as causing the sensation of itch and kappa receptors as blocking itch.[16,26] Wieczorek et al. studied hemodialysis patients and found that among patients with chronic itching that the number of kappa receptors in the skin was significantly reduced compared with patients without itching. They also noted a negative correlation between severity of itching and quantitative expression of kappa receptors.
It is important to note the interaction of the endogenous opioid and immune system. When inflammation is present, opioid sensory nerve receptors are upregulated. Moreover, mechanisms appear to exist between the immune system and perception of pain. Different opioids have differential effects depending on type and degree of inflammation. Moreover, opioid agents have been found to possess anti-inflammatory properties. This may be related to diminished secretion of certain cytokines or proinflammatory neuropeptides. Connectivity between opioid and immune system function is an area of active exploration that may have important implications for understanding pathobiology and therapy.
Curr Opin Nephrol Hypertens. 2022;31(5):435-441. © 2022 Lippincott Williams & Wilkins