Inhibiting small osmalarity-based pain via TRPV-4 ion channels
The fourth vanilloid transient receptor potential (TRPV-4), a mammalian gene that codes for a ligand-gated ion channel of the same name, is thought to be involved with the molecular signaling of pain. One of its functions is to signal the hypotonicity of the region, which is the difference in the concentration of nonpermeable solutes inside and outside of the cell. This is done in nocioreceptive neurons and thus the peripheral signal is eventually relayed to the brain.
It is believed that these receptors might contribute in some way to inflammatory and neuropathic pain. Given that this condition affects between 7 and 8 percent of the population, finding ways to mitigate the effects would be beneficial.
Alessandri-Haber et al created a mouse model of hypotonic based pain by injecting either isotonic solution or different concentrations (2% or 10%) of hypotonic saline solution and measured the amount of flinching induced. There was significantly more flinching in the hypotonic solution, which was to be expected.
Next, the researchers sensitized the hypotonic nociceptive behavior of TRPV-4 through the inflammatory mediator prostaglandin E2, so that differences based on subsequent inhibition could be more easily noticed. Then they inhibited both the TRPV-4 in both the 2% and 10% concentrations of hypotonic solution with antisense oligodeoxynucleotides (ODN).
The 2% control hyptonic solution group had 25 +/- 4 flinches compared with 14 +/- 1 for the ODN group, which was a significant effect. However, the 10% control hypotonic solution group had 41 +/- 3 flinches compared to 32 +/- 2 for the ODN group, which was not a significant effect. The researchers concluded that this method of inhibition would only be useful in treating small amounts of hypotonic-induced pain.
In a recent review, Wolfgang Liedtke suggests a few other mechanisms by which the TRPV-4 gene might affect hyperalgesia, including mechanical and thermal pathways. He also argues that blocking TRPV-4 may have some a role in lowering pain in the colon, rectum, and bladder. It seems that fighting with pain may be done in an iterative manner, and blocking TRPV-4 channels may be one step in removing unnecessary and unwanted pain.
References
Liedtke W. 2008 Molecular Mechanisms of TRPV4-Mediated Neural Signaling. Annals of the New York Academy of Sciences 1144: 42-52. doi: 10.1196/annals.1418.012.
Allesandri-Haber N, Joseph E, Dina OA, Liedtke W, Levine JD. 2005 TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediaton. Pain 118: 70-79. doi: 10.1016/j.pain.2005.07.016.