The Cutting Edge of Aspirin Research

Aspirin—one of the most widely used antipyretic analgesics. Lion is using its research into aspirin’s side effects and a new mechanism of action to develop new products.

Creating a Stomach-Friendly Analgesic

When we are injured, a signal travels from the place of the injury, through the body’s nerves to the brain, at which point we register the sensation of pain. Aspirin exerts an analgesic (pain relief) effect by suppressing the synthesis of prostaglandin (PG), a substance that amplifies these pain signals. Aspirin and other drugs that work the same way, such as loxoprofen, ibuprofen and celecoxib, are known as non-steroidal anti-inflammatory drugs (NSAIDs). Although acetaminophen is also widely used as an antipyretic analgesic, it works by a different kind of pain relief mechanism.

However, NSAIDs have the side effect of causing stomach irritation. This is because, in addition to suppressing the synthesis of PG, NSAIDs also suppress the production of gastric mucus, which protects the stomach. Because the pain relief effect and the stomach-irritating side effect are inseparable, finding ways to suppress the side effect is crucial.

Lion has explored numerous potential ways of leveraging aspirin’s analgesic effect while reducing its side effect. Early general purpose antipyretic analgesics were formulated with the antacid dialuminate (a mixture of aluminum glycinate and magnesium carbonate) to neutralize gastric acid. However, thanks to improvements made since the 1990s, aspirin products today typically contain synthetic hydrotalcite or dried aluminum hydroxide gel. These substances produce an antacid effect on par with dealuminate in smaller amounts, allowing pills or capsules to be smaller and easier to swallow.

Aspirin is also known for effects other than pain relief. One of these is an antithrombotic effect. The same mechanism that causes stomach irritation also inhibits blood clotting. However, a regular low dose of aspirin must be taken to take advantage of this effect. In 2000, Lion, with its long track record in aspirin products, obtained the first regulatory approval in Japan for the use of aspirin as an antiplatelet drug.

New Analgesic Effect Discovered

Back pain due to muscle strain, such as that caused by poor posture for extended periods, like when slouching in front of a desk, is known as myofascial pain. Recreating this type of pain with a model, Lion investigated the pain relief effects of four NSAIDs (aspirin, loxoprofen, ibuprofen and celecoxib) as well as acetaminophen. This yielded the novel finding that, while celecoxib showed no effect whatsoever, all the other ingredients did have an analgesic effect. Celecoxib exerts an analgesic effect by selectively inhibiting the enzyme cyclooxynase-2, but the other NSAIDs inhibit other enzymes in addition to cyclooxynase-2. The finding that Celecoxib did not show any effect indicates means that the analgesic effect on myofascial pain was achieved via a mechanism other than inhibiting cyclooxynase-2.

Aspirin for Knee Pain

Osteoarthritis of the knees is a disease that occurs when the knee cartilage becomes deformed or wears down, causing the structure of the joint to gradually break down, leading to persistent pain and even difficulty walking. When such pain continues for an extended period, abnormal transmissions of pain signals can occur in the spinal cord. This can cause the sensation of pain in parts of the body other than the knees and pain from even mild stimuli. This condition is called secondary hyperalgesia.

Lion studied the effect of NSAIDs and acetaminophen on secondary hyperalgesia. This led to the unexpected finding that ibuprofen, which worked well on back pain, had no effect on secondary hyperalgesia. That this type of pain could be treated not only with loxoprofen, which is commonly used for back pain, knee pain and orthopedics, but also with aspirin, which has typically been used for headaches and menstrual pain, was of great interest.

Based on its research in this area, Lion has developed over-the-counter drugs that can be taken orally to help relieve back and knee pain. Going forward, we aim to continue basic research into the mechanisms of actions of aspirin to develop new products.

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