NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might improve intractable visceral pain of cancer origin.
The cancer-related visceral pain has traditionally been frustrating to treat by either medical or surgical means. Recent investigations from bench and bedside have suggested that a critical visceral nociceptive pathway originates from post-synaptic dorsal column (PSDC) neurons located in the central area of the spinal-cord. Interruption of the PSDC pathway using different surgical approaches effectively relieves intractable visceral pain in cancer patients. However, the indications of surgical lesion of DC are very limited in clinical setting because of the surgical risks and complications. Thus, a means of high-specific pharmacological lesion of DC pathway is necessary. Some evidence has shown that spinal PSDC neurons start to express neurokinin-1 (NK-1) receptors after visceral stimulation, suggesting new targets for the development of pharmacological strategies for the control of visceral pain. Here, we present our hypothesis that the targeted cytoxin composed of substance P coupled to the cytotoxic ribosome inactivating protein, saporin, might selectively destroy spinal PSDC neurons expressing NK-1 receptors, which will lead to pharmacological interruption of PSDC pathway and will greatly improve intractable visceral pain of cancer origin. Based on the data from related research, we believe that the current therapy we propose might be one of the optimal pharmacological approaches to replace the neurosurgical interruption of DC pathway and could be used for cancer-related visceral pain in wider clinical indications.
Wang
Yun
Y
Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. sincerewy@yahoo.com
Mu
Xiaobo
X
Liu
Yang
Y
Zhang
Xuena
X
Wu
Anshi
A
Yue
Yun
Y
D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000150:complications*; D009474:Neurons / Q000473:pathology*; D010148:Intractable Pain / Q000209:etiology / Q000628:therapy*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013131:Spine / Q000473:pathology*
D018040:Receptors, Neurokinin-1