Chronic Pain

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What can cause Chronic Pain?

 Chronic pain is primarily due to a condition called hyperalgesia, or heightened sensitivity to a stimulus that would not normally be painful. Pain sensing neurons (called nociceptors) in the peripheral tissues express cation channels, called Transient Receptor Potential (TRP) channels, that open in response to noxious stimuli, contributing to the generation of an action potential, and the transmission of a pain signal to the spinal cord.  At their terminals in the spinal cord, these neurons release glutamate which activates second-order neurons that carry the signal to pain centers in the brain. The spinal cord is a major site of opioid action, where mu-opioid receptors  inhibit the release of glutamate.

PAR-2 Technology

Current Treatment options

The primary treatments for pain are over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDS) and opioids, which are effective for managing acute pain, but are less effective in treating chronic pain, and are accompanied by intolerable side effects. Opioids rapidly result in tolerance and are responsible for a large proportion of opioid-related overdoses. Thus, there is an urgent need for alternative pain medications.

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How is PAR-2 involved with Chronic Pain?

 In chronic pain conditions, signals within the cell modify TRP channels, such that they open more readily. This results in a lower threshold for activation of the nociceptors and the development of hyperalgesia. Mast cell tryptase is released at peripheral nerve endings, where it activates PAR-2, leading to sensitization of TRP channels and thus contributing to hyperalgesia. PAR-2 further amplifies the pain signal by increasing the release of excitatory neurotransmitters that activate TRP channels, and by promoting the release of inflammatory mediators, such as prostaglandins (the target of NSAIDs). PAR-2  is a promising alternative for treatment of chronic pain because it can be inhibited peripherally to prevent the sensitization of pain receptors that underlies chronic pain. In this way, we can treat both the cause and the symptoms of chronic pain.

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