Controlling the activation of the prokineticin system as therapeutic approach to relief neuropathic pain and reduce neuroinflammation

Neuropathic pain is a relevant clinical problem worldwide, since current therapeutic treatments are unsatisfactory. The identification of novel therapeutic targets and the development of new pharmacological approaches remain a priority. This pathological condition is generally triggered by an injury at peripheral or central nervous system and it is characterized by pain exacerbation and neuronal hypersensitization, resulting in abnormal pain transmission. Neuroinflammation in the peripheral and central nervous system largely contributes to neuropathic pain onset, development and maintenance. In this scenario, the recently identified chemokine family, the prokineticin system (PKS), is a promising pharmacological target for the management of neuropathic pain, considering its pronociceptive and proinflammatory properties and its role in neuronal-glia interaction. Moreover, the availability of specific receptor antagonists makes this system even more interesting in order to control prokineticin activity. In this review we report all preclinical data available on the role of PKS in the physiopathology of neuropathic pain. The results clearly suggest that drugs which block the PKS may represent an innovative and efficacious pharmacological treatment to control neuropathic pain in patients.

Impact statement

  • PK2/PKRs play a pivotal role in pain transmission.
  • Neuropathic pain state increases PK2/PKRs levels in the main pain stations.
  • Blocking PKRs with specific antagonists reduces pain and neuroinflammation.
  • Prokineticin system opens a new therapeutic avenue for neuropathic pain treatment.


Table of Content: Vol. 4 (No. 2) 2022 May/August