Both Pain, Depression Reduced by Inhibiting TRPV1 in Fibromyalgia Mouse Model, Study Shows

Both Pain, Depression Reduced by Inhibiting TRPV1 in Fibromyalgia Mouse Model, Study Shows

Inhibiting the nerve cell receptor TRPV1 led to the dual effect of reducing both pain perception and depressive-like behaviors in a mouse model of fibromyalgia, a preliminary study showed.

The study, “Involvement of TRPV1 and the efficacy of α-spinasterol on experimental fibromyalgia symptoms in mice,” was published in the journal Neurochemistry International

Fibromyalgia is characterized by widespread chronic pain. A large proportion of patients also deal with debilitating comorbidities — having two chronic diseases or conditions at the same time — such as moderate-to-severe depression and anxiety.

Conversely, people with depression report an increased perception of pain and are more likely to develop chronic pain, the researchers said. 

As these conditions often occur together, “it is highly relevant to identify a compound with a dual-action that could treat both pain and depression symptoms,” the investigators said.  

A protein receptor on the surface of cells in the nervous system — named the transient receptor potential vanilloid 1 (TRPV1) — was previously found to be implicated in the development of pain sensitivity and depressive-like behaviors. 

Moreover, blocking this receptor in mice, or removing it altogether, led to anti-depressive behavior, while TRPV1 inhibition reduced pain perception in preclinical and clinical studies. 

Despite studies showing that TRPV1 activation is associated with increased pain perception in a fibromyalgia mouse model, the effects of targeting TRPV1 with a single therapy able to treat both pain and depression has not been evaluated. 

Thus, a team of investigators based at the Federal University of Santa Maria, in Brazil, tested the known TRPV1 inhibitors α-spinasterol — a chemical found in a variety of plants — and SB-366791 in a mouse model with induced fibromyalgia. The goal was to determine if these inhibitors had an effect on pain and depressive-like behaviors. 

Fibromyalgia in the mice was induced by injecting them with the chemical reserpine, an alkaloid derived from the roots of Rauwolfia serpentine and vomitoria. This reduced the levels of brain chemicals such as dopamine, norepinephrine, and serotonin (monoamines), stimulating allodynia — increased pain sensitivity triggered by non-painful stimulation. 

Low levels of monoamines are found in many people with depression who also experience chronic pain. 

Symptoms of pain sensitivity and depressive-like behaviors, in response to the TRPV1 inhibitor treatment, were assessed using a variety of tests. 

As expected, mice treated with reserpine displayed fibromyalgia-like symptoms such as increased allodynia, muscle weakness, depressive-like behaviors, and lower monoamine levels. This validated the use of reserpine-treated mice as an experimental model for fibromyalgia.

The results showed that, following a single or 3-day repeated dose of the steroid α-spinasterol, allodynia was inhibited by almost 80%. Meanwhile SB-366791 inhibited allodynia up to 73.4%.

A low dose of the chili pepper extract capsaicin, the chemical that makes spicy food hot, was implanted in the mice’s paws. That caused the reserpine-treated mice to lick their paws, a sign of overt pain sensitivity. Both TRPV1 inhibitors reduced this behavior by up to 100%. 

Depressive-like behaviors, identified by a forced swimming test commonly used to screen antidepressant therapies, found that both TRPV1 inhibitors also reduced this behavior up to 100%. 

A final experiment, using a chemical that overstimulates the TRPV1 receptor, eventually leading to pain desensitization, confirmed that TRPV1 was responsible for the reserpine-induced fibromyalgia.

The researchers concluded that “the TRPV1 channel is involved in the development and maintenance of nociception [pain perception] and depressive-like behaviours in a fibromyalgia model, while the α-spinasterol has therapeutic potential to treat the pain and depression symptoms in fibromyalgia patients.”

“The TRPV1 antagonist α-spinasterol … might be an effective, novel approach for treating both pain and depression symptoms in fibromyalgia patients because their antinociceptive and antidepressant effects are already known,” they said.