A recent study in rats describes a new mechanism that is responsible for mediating pain in fibromyalgia (FM), providing a potential new avenue to alleviate pain symptoms in this patient population.
The study, “Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium,” was published in the journal Scientific Reports.
Previous studies suggest that the pain associated with FM is characterized by low levels of the mineral selenium, as well as excessive calcium influx, reactive oxygen species (ROS) production, and acidic pH.
Two acid- and oxidative stress-sensitive channels belong to the transient receptor potential (TRP) family: TRPM2 and TRPV1. These are calcium cation channels that, when stimulated, allow the influx of calcium into the cell.
These channels are mainly expressed in the dorsal root ganglion neural (DRGN) cells and the sciatic nerve neural (SciN) cells. These two cell types are importation for the induction of pain in FM.
Researchers used a rat model to better understand the role of the TRPM2 and TRPV1 channels in oxidative stress and acid-dependent activation of pain in FM, and the therapeutic potential of selenium.
Because FM is more common in women, the researchers used female rats. They divided 36 rats into four treatment groups: control, selenium-treated, FM rats, and FM rats treated with selenium.
When selenium was given to FM rats, there was a significant reduction in pain sensitivity in the animals. Additionally, treating rats with selenium before inducing FM could increase the sensitivity threshold, allowing the animals to endure higher levels of mechanical pain stimuli.
The researchers also showed that blocking the TRPV1 and TRPM2 channels with specific inhibitors could effectively reduce the intracellular concentration of calcium in DRGN and SciN cells.
Importantly, this effect on calcium levels could also be seen when selenium was given to rats. This suggests that selenium can regulate FM-induced calcium influx by regulating the TRPV1 and TRPM2 calcium channels in neurons.
Similarly, when stimulated by oxidative stress, an increase in calcium concentration was observed, but this effect could be minimized by treatment with selenium.
When DGRN and SciN are stimulated by ROS or other means, often these cells undergo a type of programmed cell death called apoptosis. An increase in apoptotic markers and decrease in cell viability was seen in FM-induced rats. Importantly, treatment with selenium lessened this effect and increased cell viability.
This model, therefore, provides a new understanding of the underlying causes of FM-associated pain, as well as new potential therapeutic avenues.
“The use of Se [selenium] may be an effective novel approach for treating FM-induced pain, mitochondrial oxidative stress, and apoptosis. In addition, the TRPM2 and TRPV1 channels may be important pharmacological targets in the treatment of FM-induced apoptosis and pain,” the team concluded.