New research conducted by the Hebei Medical University in China and the University of Leeds in the UK has discovered that Substance P, a natural substance that triggers pain in the central nervous system, has the opposite effect in the peripheral areas of the body. The revelation may explain the repeated failures of clinical trials of drugs that target substance P, and provide new insights into more effective means of pain management. The presence of substance P in the central nervous system has been well understood to excite neurons and promote pain sensation. By contrast, the new study found its role in the peripheral nervous system is to make nerves less responsive and excitable. Lead author Nikita Gamper, PhD, Professor of Neuroscience at University of Leeds, commented, “Substance P is described in the literature as a molecule that gets nerve cells excited and promotes pain. But we've discovered a paradox—in the peripheral nervous system it acts as one of the body's natural painkillers and actually suppresses pain.” The findings are published in Antioxidants and Redox Signalling.
In the peripheral system, substance P was found to modulate the action of a neuron-controlling protein by making it extremely sensitive to zinc, thereby suppressing neuronal activity. The authors suggest that a drug that mimics the mechanism used by substance P, and also is unable to pass the blood brain barrier into the central nervous system, which could thus offer more effective pain suppression without the side effects of opioid medications. The current study of nerve responses in animal models focused on acute pain, but follow-on research will examine the role of Substance P in chronic pain as well.
Read more about substance P, here.
A news story about the findings, with a link to the journal article, may be read here.