Saint Louis University (SLU) researchers report progress on their mission to find a non-narcotic off switch for pain. In a recent study, they share their understandings about how neuropathic pain occurs at the cellular and molecular level and how it can be turned off in a laboratory setting.
The research, published recently in Proceedings of the National Academy of Sciences (PNAS), could a foundation for the development of new non-opioid pain-killing therapies, they suggest.
Daniela Salvemini, PhD, professor of pharmacology and physiology and director of The Henry and Amelia Nasrallah Center for Neuroscience at Saint Louis University, notes that neuropathic pain can be exceedingly difficult to treat.
“Neuropathic pain can be severe and does not always respond to treatment,” Salvemini says, in a media release from Saint Louis University.
“Opioid pain killers are widely used but can cause strong side effects and carry risks of addiction and abuse. There is an urgent need for better options for patients suffering from chronic pain.”
Building on previous research, Salvemini and her colleagues found that a particular cellular receptor appears to be the culprit in the development of traumatic nerve injury pain in an animal model.
In response to a nerve injury, the body generates a molecule called sphingosine-1-phosphate (S1P) in the dorsal horn of the spinal cord. S1P, in turn, can activate the receptor protein sphingosine 1-phosphate receptor subtype 1 (S1PR1) on the surface of specialized nervous system support cells called astrocytes, resulting in neuroinflammation.
In fact, pain pathways appear to depend on the activation of S1PR1; conversely, blocking this signal limits or stops pain, the release explains.
“This study clearly establishes that S1P activation of S1PR1 signaling in astrocytes is required for the development and maintenance of traumatic nerve injury-induced neuropathic pain,” Salvemini comments.
“Several important findings have emerged from our studies. We unequivocally established that activation and not inhibition of S1PR1 drives and maintains neuropathic pain. Consequently, turning S1PR1 off — not on — is required to inhibit the development of neuropathic pain and to reverse it once established.”
These findings lay the groundwork to develop a new class of medications that offer pain-killing benefits without the risks and side-effects of opioids, the release suggests.
“It is noteworthy that drugs that inhibited S1PR1 did not lose their beneficial effects during prolonged use nor did they engage the molecular pathways opioids use, suggesting that targeting S1PR1 is unlikely to cause opioid-like abuse,” Salvemini concludes.
“Collectively, our results establish S1PR1 as a good target for developing new therapies, creating a new class of non-narcotic pain-killers.”
[Source(s): Thomas Jefferson University, EurekAlert]
