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Scientists make white blood cells to alleviate pain, instead of producing it, during tissue inflammation in mice

Researchers at the University of Granada lead a novel study in mice that shows that sigma‑1 receptor blockers cause white blood cells or leukocytes to relieve the pain felt when a tissue is inflamed

His work was published in July in the renowned PNAS journal

Immune system cells (leukocytes or white blood cells) accumulate in the tissues of the human body, for example, after suffering a trauma or a wound. Their main function is repairing the damaged tissue. However, in addition to that function, those cells release certain substances that produce pain (called algogenic chemicals), so they play a key role in the pain felt when the tissue is inflamed. This is also applicable to certain chronic pathologies that present inflammation and pain, as is the case of arthritis.

Paradoxically, these leukocytes, in addition to releasing algogenic chemicals, are capable of producing endogenous opioid peptides (such as endorphins). Said peptides have the same activity as opioid analgesics (drugs for treating intense pain, such as morphine), used for millennia for treating pain. However, the balance between the analgesic and the pain‑inducing activity of leukocytes during inflammation clearly favors pain; in fact, inflammation produces pain.

The sigma‑1 receptor is a very small protein present in neurons, and is capable of modulating the action of opioid receptors. A study led by scientists from the University of Granada (UGR) has discovered that sigma‑1 receptor blockers are capable of increasing the effect of endogenous opioid peptides produced by leukocytes, so that these cells relieve pain instead of producing it when they are in the inflamed tissue. The team of researchers belongs to the Department of Pharmacology and the Institute of Neuroscience, Biomedical Research Center (UGR), and has counted with the collaboration of the pharmaceutical company Esteve, the Teófilo Hernando Institute for Drug Discovery, and the Institute of Molecular Biotechnology of Austria.

“We present a totally novel pain relief mechanism, based on maximizing the analgesic potential of the immune system cells, and which could have important therapeutic applications in patients with pain of inflammatory origin”, says the director of this work, professor Enrique J. Cobos del Moral, researcher from the Department of Pharmacology and the Institute of Neuroscience of the University of Granada.

This research work has been possible thanks to the Program for the Reincorporation of Doctors, promoted by the Vice-Rectorate for Research and Transfer of the UGR.

Bibliographic references:

  1. Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice Miguel. A. Tejada, Angeles Montilla-García, Shane J. Cronin, Domagoj Cikes, Cristina Sánchez-Fernández, Rafael González-Cano, M. Carmen Ruiz-Cantero, Josef M. Penninger, José M. Vela, José M. Baeyens and Enrique J. Cobos. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2017.




  1. The UGR research team that carried out this study. From left to right: Miguel Ángel Tejada Giráldez, Ángeles Montilla García, M Carmen Ruiz Cantero and Enrique J. Cobos del Moral.


NdP 27 - Leucocitos analgésicos (1)

2. Role of the sigma‑1 receptor in inflammatory pain. (A) Leukocytes present in the inflamed site release algogenic chemicals that contribute to pain, along with endogenous opioid peptides. Said opioid peptides do not relieve pain because the sigma‑1 receptor inhibits the functioning of opioid receptors. (B) Sigma‑1 blockers remove the brake on the functioning of opioid receptors, thus resulting in pain relief.


Enrique J. Cobos del Moral

Department of Pharmacology | Institute of Neuroscience, UGR

Phone number: (+34) 958 24 93 02