Potential New Therapeutic Targets for Pathological Pruritus

Abstract

Very few approved medications are indicated for the treatment of pruritus, and drug development for pruritic diseases is awaited. During the past two decades, progress has been made in understanding the molecular basis of the physiology and pathophysiology of pruritus. Newly identified potential targets for pathological pruritus include receptors (histamine H 4 receptor, leukotriene B 4 receptors, interleukin-31 receptor A, bombesin BB 2 receptor, toll-like receptor 3, α-adrenoceptor, and opioid μ-and κ-receptors), channels (transient receptor potential (TRP) V3 and TRPA1 channels), and enzymes (histidine decarboxylase, sphingomyelin glucosylceramide deacylase, 5-lipoxygenase, leukotriene A 4 hydrolase, and autotaxin). The development of specific, effective blockers and agonists/antagonists of these targets is awaited.

Milnacipran Inhibits Itch-Related Responses in Mice Through the Enhancement of Noradrenergic Transmission in the Spinal Cord

“…Since the itching or scratching response involves sensory pathways and is associated with a spinal reflex (scratch reflex), inhibition of the production of itch signals in the peri phery is an ideal pharmacological intervention for pruri ceptive itching. However, it may be difficult to ameliorate itching seen in all pruritic diseases by inhibiting the peripheral pathways because various itch mediators are involved in pathological pruritus (2). Thus, inhibition of itch signal transmission in the dorsal horn represents an important mode of action for antipruritic drugs (2).…”

“…However, it may be difficult to ameliorate itching seen in all pruritic diseases by inhibiting the peripheral pathways because various itch mediators are involved in pathological pruritus (2). Thus, inhibition of itch signal transmission in the dorsal horn represents an important mode of action for antipruritic drugs (2).…”

Antipruritic effect of cold stimulation at the Quchi Acupoint (LI11) in Mice

“…Similarities are observed between the neural pathways responsible for itching, pain and temperature, which explains the ability of various temperatures to modulate the desire to scratch. Therefore, TRP channels could serve as important but complex clinical targets for pruritus therapy [46]. In the present study, we suggest the different thermal stimulation acting different TRP ion channels which play important role of the antipruritic effect.…”

Inflammatory cytokines and peripheral mediators in the pathophysiology of pruritus in cutaneous T‐cell lymphoma

“…However, these commonly prescribed antihistamines primarily act on the H1 receptor. There is still the possibility of a pruritogenic pathway mediated by H3 and H4 receptors, but the role of these receptors in pruritus remains unknown …”