Arthropods attack organisms by biting, stinging, piercing, and sucking. Among the various arthropods that affect human health by feeding on living hosts, piercing by mosquitoes spreads parasites and viruses, some of which have been reported to cause the highest number of deaths annually, including malaria, dengue fever, and West Nile fever. Mosquito piercings are painless due to the thinness of their fascicle. Their fascicle is divided into needle of 6 stylets which also contributes to the painless piercing. Although the microneedle properties of the fascicle are currently believed to explain the painless piercings by mosquitoes, it is possible that mosquito saliva might also contribute to this lack of pain.
In general, natural painkillers are very rare, and researchers hope that this recent find might be harnessed as a clinical treatment. Naturally produced painkillers might help to avoid some of the side effects experienced by patients treated with synthetic compounds such as morphine, including addiction and tolerance with prolonged use. In a new study published recently in the Journal Pain, researchers from the National Institute for Physiological Sciences in Japan, Dr. Sandra Derouiche, Dr. Tianbang Li, and Professor Makoto Tominaga carried out the research to discover novel and safe antinociceptive agents that may be present naturally in mosquito’s saliva. They hypothesized that mosquito saliva also contains antinociceptive substances that contribute to their painless piercings. Dr. Yuya Sakai and Professor Seiji Aoyagi at Kansai University and Dr. Daisuke Uta at University of Toyama were also co-authors and contributed to the study.
Mosquito saliva should, under normal circumstances, operate on the sensory neurons that innervate the epidermis. Several ion channels, including transient receptor potential (TRP) channels are expressed in these sensory nerve terminals and may detect unpleasant stimuli. TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) were reported to be triggered by mechanical stimuli, which is thought to function during mosquito piercing, as well as unpleasant chemicals or high temperature in HEK293T cells. The authors looked at the antinociceptive effects of mosquito head homogenates and mouse saliva both in-vitro and in-vivo by focusing on TRPV1 and TRPA1 channels.
The research team observed that mosquito head homogenates containing saliva and mouse saliva exhibit antinociceptive effects through the inhibition of TRPV1 and TRPA1 channels. Further the authors found that both mosquito heads with salivary glands and mouse saliva inhibited TRPV1 and TRPA1, it is possible that saliva’s antinociceptive abilities are universal, which could explain why many species, including humans, lick their wounds. Mosquito head homogenates and mouse saliva showed a strong inhibition of TRPV1 and TRPA1 in patch-clamp recordings of HEK293T cells and mouse DRG neurons. The mosquito head homogenates induced a significant decrease in pain-related behaviors in mice, supporting the antinociceptive action of mosquito saliva through TRPV1 and TRPA1 channels. Previously Sialorphin has been reported to be an endogenous salivary antinociceptive modulator. However, it cannot be ruled out that the possibility of substances contained in saliva other than sialorphin contribute to the saliva induced antinociception because the reported sialorphin concentrations in rat saliva are smaller than the IC50 values inhibiting TRPV1 or TRPA1 activities in the study.
In a nutshell, the new study might lead to the development of new class of innovative and safe antinociceptive agents. The authors successfully demonstrated that natural substances with defined mechanism of action present in mosquito and mouse saliva, including sialorphin, can lead to discovery and development of novel and safe analgesic agents that can be used clinically for the treatment of pain.
Credit: Prof. Aoyagi (Kansai University).
Derouiche S, Li T, Sakai Y, Uta D, Aoyagi S, Tominaga M. Inhibition of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 by mosquito and mouse saliva. Pain. 2022 Feb 1;163(2):299-307.